مصادر الباحث العلمي في الجمناستك

Dr Mouwafak Majeed Mola Documents | 2012-2013

‫سلسلة الدكتور موفق مجيد المولى لتطوير الفكر البحثي العربي‬

‫الرياضي‬

‫مصادر الباحث العلمي في رياضة‬ )2(‫الجمباز‬ Special Project coordinator – Aspire Academy member of Development Committee – QFA Mouwafak Majeed Mola

2013-2012

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Occurrence of acute lower limb injuries in artistic gymnasts in relation to event and exercise phase P Kirialanis, P Malliou, A Beneka, and K Giannakopoulos Author information ► Copyright and License information ► This article has been cited by other articles in PMC. Abstract Objectives: To record the incidence of lower limb injuries (acute and overuse syndromes) in Greek artistic gymnasts in relation to the event and exercise phase.

Methods: A total of 162 gymnasts (83 male and 79 female athletes) participating in the Greek artistic gymnastic championships were observed weekly for the 1999–2000 season.

Results: Ninety three (61.6%) acute injuries and 58 (38.4%) overuse syndromes were recorded. The most common anatomical location was the ankle (69 cases, 45.7%), followed by the knee (40 cases, 26.5%). The rate of mild injuries was 26.6% (25 cases), that of moderate injuries was 44% (41 cases), and that of major injuries was 29% (27 cases). The incidence of injury to the ankle and knee was significantly higher in the floor exercise, especially during the landing phase, than in the other events.

Conclusions: By its nature, gymnastics predisposes to acute injuries, but up to 75% are mild or moderate. Special attention should be paid to the floor exercise, especially the landing phase.

Full Text The Full Text of this article is available as a PDF (111K).

Selected References These references are in PubMed. This may not be the complete list of references from this article. 

Meeusen R, Borms J. Gymnastic injuries. Sports Med. 1992 May;13(5):337–356.[PubMed] 1

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Kolt GS, Kirkby RJ. Epidemiology of injury in elite and subelite female gymnasts: a comparison of retrospective and prospective findings. Br J Sports Med. 1999 Oct;33(5):312–318. [PMC free article][PubMed] Hutchinson MR, Ireland ML. Knee injuries in female athletes. Sports Med. 1995 Apr;19(4):288–302.[PubMed] Pettrone FA, Ricciardelli E. Gymnastic injuries: the Virginia experience 1982-1983. Am J Sports Med. 1987 Jan-Feb;15(1):59– 62.[PubMed] Tenvergert EM, Ten Duis HJ, Klasen HJ. Trends in sports injuries, 1982-1988: an in-depth study on four types of sport. J Sports Med Phys Fitness. 1992 Jun;32(2):214–220.[PubMed] Lindner KJ, Caine DJ. Injury patterns of female competitive club gymnasts. Can J Sport Sci. 1990 Dec;15(4):254–261.[PubMed] Wadley GH, Albright JP. Women's intercollegiate gymnastics. Injury patterns and "permanent" medical disability. Am J Sports Med. 1993 Mar-Apr;21(2):314–320.[PubMed] de Loës M. Medical treatment and costs of sports-related injuries in a total population. Int J Sports Med. 1990 Feb;11(1):66–72.[PubMed] Ekstrand J, Gillquist J. Soccer injuries and their mechanisms: a prospective study. Med Sci Sports Exerc. 1983;15(3):267– 270.[PubMed] Ekstrand J, Gillquist J, Möller M, Oberg B, Liljedahl SO. Incidence of soccer injuries and their relation to training and team success. Am J Sports Med. 1983 Mar-Apr;11(2):63–67.[PubMed] Ekstrand J, Tropp H. The incidence of ankle sprains in soccer. Foot Ankle. 1990 Aug;11(1):41–44.[PubMed] Garrick JG, Requa RK. Epidemiology of women's gymnastics injuries. Am J Sports Med. 1980 Jul-Aug;8(4):261–264.[PubMed] Bale P, Goodway J. Performance variables associated with the competitive gymnast. Sports Med. 1990 Sep;10(3):139–145.[PubMed] Caine D, Cochrane B, Caine C, Zemper E. An epidemiologic investigation of injuries affecting young competitive female gymnasts.

Am J Sports Med. 1989 Nov-Dec;17(6):811–820.[PubMed]

Family physicians and sports-injury care. Perceptions of coaches.

I. Vergeer 2

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Author information â–ş Copyright and License information â–ş This article has been cited by other articles in PMC. Abstract OBJECTIVE: To describe coaches' education in injury care and management and their club's access to medical care, to describe coaches' perceptions of how family physicians care for sports injuries, and to describe strategies used for overcoming perceived poor advice. DESIGN: A telephone survey using both closed and open-ended questions was conducted. Information was collected as background information to a larger study investigating coaches' decisions about allowing injured athletes to compete. SETTING: All 28 competitive gymnastics clubs in the province of Alberta. The clubs trained athletes for all competitive levels.

PARTICIPANTS: All 70 coaches registered with the Alberta Gymnastics Federation as working with female gymnasts were approached; 64 coaches were interviewed. MAIN OUTCOME MEASURES: Injury education, access to medical care, perceptions of sports-injury treatment provided by family physicians, strategies employed for overcoming perceived poor advice. RESULTS: Education in injury care and management was varied, as was access to medical care. Direct access to sport-specific medical care was available at three of the five elite-level clubs, an arrangement stemming from dissatisfaction with the conventional health care system. At all competitive levels, most coaches were dissatisfied with the recommendations they received from family physicians. Various strategies were employed to acquire more suitable advice. CONCLUSIONS: The results point to a need for improved communication between family physicians and coaches.

Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

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Selected References These references are in PubMed. This may not be the complete list of references from this article. 

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Flint FA, Weiss MR. Returning injured athletes to competition: a role and ethical dilemma. Can J Sport Sci. 1992 Mar;17(1):34– 40.[PubMed] Lindaman LM. Physician care for interscholastic athletes in Michigan.

Am J Sports Med. 1991 Jan-Feb;19(1):82–87.[PubMed] Kerrigan DC, Janes WW, Martin WA, Roe TJ. Physical medicine and rehabilitation residents' educational needs assessment. Arch Phys Med Rehabil. 1993 Jul;74(7):687–690.[PubMed] Wiley JP, Strother RT, Lockyer JM. Sports medicine electives. Are they available in Canadian family medicine programs? Can Fam Physician. 1993 Aug;39:1742–1744. [PMC free article][PubMed]

Articles from Canadian Family Physician

Stress inoculation training: a case study in gymnastics.

R Mace, C Eastman, and D Carroll Copyright and License information ► Abstract 17

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A young female gymnast of regional squad potential had ceased to make progress when she resumed training after a series of injuries and was given stress inoculation training to help her to regain her form. Preliminary interviews revealed that she had developed a number of negative selfstatements and images which, it was hypothesised, may have been contributing towards her lack of progress. In order to replace these with positive self-statements and images a treatment programme of eight training sessions was implemented. Recorded interviews and subsequent comparison of comments made by the subject before and after the intervention programme, indicated that the training had been successful. This was endorsed by the coaches who reported an improved attitude to training and rapid progress in skill learning.

Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (628K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

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Selected References These references are in PubMed. This may not be the complete list of references from this article. 

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Fenz WD, Jones GB. Cardiac conditioning in a reaction time task and heart rate control during real life stress. J Psychosom Res. 1974 Jun;18(3):199–203.[PubMed] Yaffé M. The contribution of clinical psychology to sports medicine.

Br J Sports Med. 1981 Mar;15(1):60–63. [PMC free article][PubMed

A rare fracture-dislocation of the hip in a gymnast and review of the literature J. C. Mitchell, P. V. Giannoudis, P. A. Millner, and R. M. Smith Copyright and License information ► This article has been cited by other articles in PMC. Abstract Posterior fracture-dislocation of the hip is an uncommon injury in athletics and leisure activities. It is more commonly seen in high energy motor vehicle accidents and occasionally in high energy sporting activities. A rare case is reported of posterior fracture-dislocation of the hip joint that occurred in a young athlete during gymnastics. This unusual mechanism of injury illustrates the great forces sustained by the hip joint of gymnasts. Early reduction and operative treatment led to a congruent and stable hip joint.

After rehabilitation, she returned to light sporting activities after six months.

Full Text The Full Text of this article is available as a PDF (70K).

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These references are in PubMed. This may not be the complete list of references from this article. 

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Baker BE, Bierwagen D. Rupture of the distal tendon of the biceps brachii. Operative versus non-operative treatment. J Bone Joint Surg Am. 1985 Mar;67(3):414–417.[PubMed] Vastamäki M, Brummer H, Solonen KA. Avulsion of the distal biceps brachii tendon. Acta Orthop Scand. 1981 Feb;52(1):45–48.[PubMed] Fitzgerald SW, Curry DR, Erickson SJ, Quinn SF, Friedman H. Distal biceps tendon injury: MR imaging diagnosis. Radiology. 1994 Apr;191(1):203–206.[PubMed] DAVIS WM, YASSINE Z. An etiological factor in tear of the distal tendon of the biceps brachii; report of two cases. J Bone Joint Surg Am. 1956 Dec;38-A(6):1365–1368.[PubMed] Morrey BF, Askew LJ, An KN, Dobyns JH. Rupture of the distal tendon of the biceps brachii. A biomechanical study. J Bone Joint Surg Am. 1985 Mar;67(3):418–421.[PubMed] Postacchini F, Puddu G. Subcutaneous rupture of the distal biceps brachii tendon; a report on seven cases. J Sports Med Phys Fitness.

1975 Jun;15(2):81–90.[PubMed] Agins HJ, Chess JL, Hoekstra DV, Teitge RA. Rupture of the distal insertion of the biceps brachii tendon. Clin Orthop Relat Res. 1988 Sep;(234):34–38.[PubMed] Barnes SJ, Coleman SG, Gilpin D. Repair of avulsed insertion of biceps. A new technique in four cases. J Bone Joint Surg Br. 1993 Nov;75(6):938–939.[PubMed] Leighton MM, Bush-Joseph CA, Bach BR., Jr Distal biceps brachii repair. Results in dominant and nondominant extremities. Clin Orthop Relat Res. 1995 Aug;(317):114–121.[PubMed] Jacob JR, Rao JP, Ciccarelli C. Traumatic dislocation and fracture dislocation of the hip. A long-term follow-up study. Clin Orthop Relat Res. 1987 Jan;(214):249–263.[PubMed] Letournel E. Acetabulum fractures: classification and management.

Clin Orthop Relat Res. 1980 Sep;(151):81–106.[PubMed] O'Leary C, Doyle J, Fenelon G, Ward F. Traumatic dislocation of the hip in Rugby Union football. Ir Med J. 1987 Oct;80(10):291– 292.[PubMed] Stanisavljevic S, Irwin RB, Brown LR. Orthopedic injuries in waterskiing: etiology and prevention. Orthopedics. 1978 MarApr;1(2):125–129.[PubMed] 25

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Bass A, Lovell ME. Two cases of acetabular fractures sustained during competitive cycling. Br J Sports Med. 1995 Sep;29(3):205– 206. [PMC free article][PubMed] Wolfe MW, Brinker MR, Cary GR, Cook SD. Posterior fracturedislocation of the hip in a jogger. J South Orthop Assoc. 1995 Summer;4(2):91–95.[PubMed] Rydell N. Biomechanics of the hip-joint. Clin Orthop Relat Res. 1973 May;(92):6–15.[PubMed] Pearson DE, Mann RJ. Traumatic hip dislocation in children. Clin Orthop Relat Res. 1973 May;(92):189–194.[PubMed] Kuner EH. Indikation, Technik und Komplikationen der operativen Behandlung von Hüftpfannenbrüchen. Orthopade. 1997 Apr;26(4):327–335.[PubMed

Scapholunate interosseus ligament tears in elite gymnasts Matthew G. Snider,* Khalid A. Alsaleh,† and Jung Y. Mah‡ Author information ► Copyright and License information ► Gymnastics requires conversion of the upper limb into a load-bearing extremity, leading to upper extremity, especially wrist, injuries. The “gymnast's wrist” or the Madelung-like deformity involves repetitive excessive loading of immature bones leading to premature closure of the distal radial physis with associated ulna-plus variance and wrist pain.1–3 The significant physical demands of gymnastics and the frequency of injuries especially in elite gymnasts has led some to state that chronic gymnastic injuries should more properly be referred to as consequences of participation in the sport, implying the inevitability of chronic injuries.4 Up to 88% of gymnasts experience wrist pain.1 This is associated with older age, increased training hours and higher skill level.5 Elite gymnasts have a significantly greater rate of injuries than lower level gymnasts. 6 Therefore they need to be considered as a separate group from casual participants in terms of sport-specific stresses and resulting injuries.

The scapholunate interosseus ligament (SLIL) is involved in maintaining the stability of the complex structure of the wrist. Wrist injuries commonly 26

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involve the SLIL.7 However, there is no reported literature on SLIL injuries in gymnasts. It may be that these injuries have been overlooked in the past.

The wrist pain associated with these injuries is usually chronic and is less severe than a fracture, so athletes may interpret it as a nonsignificant sprain and may not seek medical attention. Physicians may overlook these injuries for similar reasons.

The mechanism of injury is generally believed to be impact loading with the wrist in extension and ulnar deviation,8,9 resulting in the capitate being driven between the scaphoid and lunate bones. This can occur with either a fall on an outstretched hand or repeated loading with weight bearing through the upper extremities. Clinical presentation is usually pain over the dorsal and radial aspects of the wrist with associated loss of motion or grip strength, or both.

Radiologically, scapholunate diastasis is defined as greater than 3 mm with a normal scapholunate distance of 2 mm or less on the other wrist. Diastasis is present in static scapholunate dissociation but is not visible in dynamic instability unless elicited on stress views, which can be performed with fist clenching or ulnar deviation of the wrist. Additional radiographic signs include the cortical “ring” sign due to the volar flexion of the scaphoid, a scapholunate angle greater than 70° (normal 30°–60°), and a radiolunate angle greater than 5°, which indicates a dorsal intercalated segmental instability (DISI) pattern with a dorsiflexed lunate. Radiographs in most scapholunate injuries appear normal, the radiographic findings already described being seen mostly in complete ligament tears or chronic partial tears.

Further evaluation can include MRI, which can better visualize scapholunate diastasis, ligament tears, occult fractures, and bone bruising. Arthrography has been used but often now is bypassed in favour of arthroscopy, which continues to be the standard method for evaluating SLIL injuries.

We describe 3 patients who had tears of the scapholunate ligament.

Go to: Case reports Case 1 27

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A 21-year-old right-hand dominant man from the Canadian national gymnastics team presented with a 3-month history of pain over the dorsal aspect of his right wrist that made training impossible. The pain was worsened by activities that axially loaded his wrist, such as the pommel horse. Physical examination revealed ulnocarpal joint tenderness. No effusion was palpable. CT showed a small minimally displaced fracture on the dorsal aspect of the triquetrum. Wrist radiographs appeared normal.

Bone scanning showed mild uptake of radoactive material at the radiocarpal junction and mild–moderate uptake in the triquetrum/pisiform region and the radial intercarpal region of the right wrist. Subsequently, magnetic resonance arthrography showed a scapholunate ligament tear, with contrast material extending into the midcarpal joint and associated DISI. Contrast material also extended along the medial aspect of the distal ulna consistent with an ulnar collateral ligament tear. A small avulsed bone fragment was confirmed dorsal to the triquetrum.

Arthroscopy of the wrist (Fig. 1) revealed that the scapholunate ligament was approximately 50% torn, with a scapholunate distance of approximately 4 mm. Osteoarthritis of the scapholunate joint and synovitis were debrided.

Joint debris was removed. The triangular fibrocartilage complex (TFCC) was not torn.

FIG. 1. Case 1. Wrist arthroscopy demonstrating disruption of the scapholunate interosseus ligament.

Wrist exercises were prescribed and the man subsequently obtained a full range of motion of his wrist. Recommendations were made to wait 3 months before resuming training.

Case 2 A 19-year-old man from the Canadian national gymnastics team presented with pain over the dorsal aspect of his left wrist. There was dorsal tenderness on the ulnar side but not over the TFCC. Radiographs appeared normal.

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Magnetic resonance arthrography indicated a possible focal tear within the mid-or volar portion of the scapholunate ligament. A minute amount of contrast material entered the mid-carpal joint. Ultrasonography confirmed that the dorsal portion of the scapholunate ligament was intact.

He continued to have symptoms and was unable to continue his training.

Arthroscopy was performed for diagnostic reasons. A partial scapholunate ligament tear was discovered along with chondromalacia of the scaphoid, lunate and distal radius (Fig. 2). Therefore, arthroscopic debridement was performed.

FIG. 2. Case 2. Wrist arthroscopy demonstrates chondromalacia of the scaphoid and lunate as well as disruption of the scapholunate interosseus ligament.

His symptoms improved and he was able to resume training.

Case 3 A 15-year-old boy from the Canadian national gymnastics team presented with ulnar-sided left wrist pain. His pain was worsened with activities such as the pommel horse that axially loaded his wrist. There was tenderness and a full range of motion of the wrist. Radiographs appeared normal.

Magnetic resonance arthrography showed an area of altered signal within the lunate that could not exclude a small bone bruise or avascular necrosis. A subsequent bone scan appeared normal.

He continued to train and compete but his significant wrist pain persisted.

Arthroscopy detected a partial full-thickness tear of the scapholunate ligament, chondromalacia of the lunate and fraying of the ulnar collateral ligament.

After arthroscopic debridement his wrist symptoms improved and he was able to continue training.

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Discussion The high physical demands of elite gymnastics on the upper extremity produce the potential for significant injuries. In addition to acute wrist injuries, skeletally immature athletes can suffer chronic wrist injuries, ranging from stress fractures through the physis of the distal radius to ulnarplus deformities related to premature growth arrest due to excessive loading through the physis. Ligamentous injuries can occur either acutely or chronically and affect either the extrinsic or intrinsic ligaments of the wrist.

These injuries are considered as minor injuries or overuse syndromes.

We hypothesize that the ligament injuries and degenerative changes we have reported in our 3 cases are related to twisting, dismount-type activities in gymnastics that place maximal stress on the radial column of the wrist.

All 3 athletes were managed with arthroscopy and debridement after appropriate imaging had been conducted. Wrist supports limiting excessive dorsiflexion of the wrist were recommended and worn by each athlete for training and competitions. All athletes were able to return to full training.

Given the likely mechanism of injury of dorsiflexion and ulnar deviation of the wrist and the frequent upper extremity loading occurring in this posture in gymnastics, it may be advisable in the future to consider the use of dorsiflexion-limiting wrist supports to prevent scapholunate ligament tears.

Go to: Notes This study was conducted at McMaster University Medical Centre, Hamilton, Ont. Competing interests: None declared.

Correspondence to:Dr. Jung Mah, 674 Upper James St., Hamilton ON L9C 2Z6; fax 905 575-1799 Go to: References

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1. Dobyns JH, Gabel GT. Gymnast's wrist. Hand Clin1990;6:493-505.

[PubMed] 2. De Smet L, Claissens A, Fabry G. Gymnast wrist. Acta Orthop Belg1993;59:377-80. [PubMed] 3. Tolat AR, Sanderson PL, De Smet L, et al. The gymnast's wrist: acquired positive ulnar variance following chronic epiphyseal injury. J Hand Surg [Br] 1992;17:678-81.

4. Gabel GT. Gymnastic wrist injuries. Clin Sports Med1998;17:611-21.

[PubMed] 5. DiFiori JP, Puffer JC, Mandelbaum BR, et al. Factors associated with wrist pain in the young gymnast. Am J Sports Med1996;24:9-14. [PubMed] 6. McAuley E, Hudash G, Shields K, et al. Injuries in women's gymnastics.

The state of the art. Am J Sports Med1987;15:558-65. [PubMed] 7. Jones WA. Beware the sprained wrist: the incidence and diagnosis of scapholunate instability. J Bone Joint Surg Br1988;70:293-7. [PubMed] 8. Mayfield JK, Johnson RP, Kilcoyne RK. Carpal dislocations: pathomechanics and progressive perilunar instability. J Hand Surg [Am] 1980;5:226-41.

9. Johnson RP. The acutely injured wrist and its residuals. Clin Orthop Relat Res 1980;(149):33-44.

Bone Geometry, Density and Strength Indices of the Distal Radius Reflect Loading via Childhood Gymnastic Activity Jodi N. Dowthwaite, Ph.D.,1 Portia P.E. Flowers, B.A.,2 Joseph A. Spadaro, Ph.D.,1 and Tamara A. Scerpella, M.D.1 Author information â–ş Copyright and License information â–ş The publisher's final edited version of this article is available at J Clin Densitom See other articles in PMC that cite the published article.

Go to: Abstract The distal radius bears unique forces during gymnastic activity. Its relatively simple anatomy, minimal soft tissue envelope and varied composition make the distal radius ideal for evaluating the effects of loading on bone properties. For 56 premenarcheal gymnasts and non-gymnasts, ultradistal and 1/3 distal radius DXA scans measured bone mineral content (BMC), areal bone mineral density and projected area. Simplified geometric models 31

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were used to generate bone mineral apparent density (BMAD), geometric indices, strength indices and fall strength ratios. Ratios of regional BMC vs. total body fat free mass (FFM) were calculated. Separate Tanner I and II analyses of covariance adjusted bone parameters for age and height. Ratios were compared using maturity-matched analyses of variance. At the 1/3 region, periosteal width, BMC, cortical cross-sectional area, and section modulus were greater in gymnasts than non-gymnasts (p<0.05); 1/3 BMAD means were equivalent. Ultradistal BMAD, BMC and index for structural strength in axial compression were higher in gymnasts than non-gymnasts; ultradistal periosteal width was only larger in Tanner I gymnasts. Fall strength ratios and BMC/FFM ratios were greater in gymnasts (p<0.05).

Geometric and volumetric responses to mechanical loading are site-specific during late childhood and early adolescence.

The distal radius bears unique forces during gymnastic activity, and fan beam magnification error is negligible at this site, making it ideal for DXA evaluation of associated bone properties. For 56 premenarcheal gymnasts and non-gymnasts, ultradistal and 1/3 distal radius DXA scans measured bone mineral content, areal bone mineral density and projected area.

Simplified geometric models were used to generate bone mineral apparent density, geometric indices, strength indices and fall strength ratios. Ratios of regional bone mineral content vs. total body fat free mass were calculated.

Separate Tanner I and II analyses of covariance adjusted bone parameters for age and height. Ratios were compared using maturity-matched analyses of variance. At the 1/3 region, periosteal width, bone mineral content, cortical cross-sectional area, and section modulus were greater in gymnasts than non-gymnasts (p<0.05); 1/3 bone mineral apparent densities were equivalent. Gymnastsâ&#x20AC;&#x; ultradistal bone mineral apparent density, bone mineral content and index for structural strength in axial compression were higher; ultradistal periosteal width was only larger in Tanner I gymnasts.

Fall strength ratios and bone mineral content vs. fat-free mass were greater in gymnasts (p<0.05). Gymnastsâ&#x20AC;&#x; geometric and volumetric responses to mechanical loading are site-specific during late childhood and early adolescence.

Keywords: bone density, bone size, gymnasts, radius, growth, exercise Go to: INTRODUCTION

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To date, most studies that evaluate the effect of mechanical loading on bone growth have focused on areal bone mineral density (aBMD) and bone mineral content (BMC), rather than on bone geometry. When considered, bone size is often used solely to adjust for the confounding effects of body size variation upon BMC or BMD, rather than as an outcome measure that varies as a function of physical activity. Few investigators have attempted to evaluate bone geometry in response to exercise; as a result, limited evidence has been provided for an effect of mechanical loading on bone architecture (1â&#x20AC;&#x201C;7). Even fewer studies have demonstrated geometric adaptation to mechanical loading during growth (8â&#x20AC;&#x201C;12).

Artistic gymnastics has been studied extensively as a model for the skeletal effects of impact loading. Because the unique weight-bearing function of the upper extremity in gymnastics is infrequently duplicated by other activity, the forearm is a particularly useful site for these evaluations. Within the forearm, the radius bears the brunt of impact forces, thereby providing a specific barometer of impact/weight-bearing activity experienced during gymnastics. In addition, the radius contains regions of bone that are predominantly cortical or predominantly trabecular, allowing for comparisons of bone tissue-specific responses. Compared to the more complex anatomy of the proximal femur or lumbar spine, the structure of the radius facilitates the use of a simplified model to derive geometric measures, bone mineral apparent density (BMAD), and indices of strength (13).

Finally, in the distal forearm, there is negligible variation in soft tissue envelope dimensions; thus, variation in distance from the x-ray source and resultant fan-beam magnification error are both uniform and minimal (14).

Many studies have identified higher aBMD in gymnasts than non-gymnasts at the forearm and other weight-bearing sites (15â&#x20AC;&#x201C;20); only one has explored the relative contributions of geometry and volumetric density (11). Previous analyses by our group demonstrated significantly higher areal BMD at the forearm in premenarcheal gymnasts relative to maturity-matched nongymnasts; these differences persisted after adjustment for age, height and total body FFM (15). We hypothesized that variation in aBMD was due to both geometric and densitometric adaptations to impact loading, and that the ultradistal (metaphyseal, trabecular bone) and 1/3 (diaphyseal, cortical bone) regions of the radius would express these adaptations differently. The present study expands upon our prior work, reassessing scans from the established cohort in order to elucidate geometric, material, and strength 33

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properties of the ultradistal and 1/3 distal radius in premenarcheal gymnasts and non-gymnasts.

Go to: MATERIALS AND METHODS Subjects represent a premenarcheal subset of 56 participants from an ongoing, longitudinal study of female artistic gymnasts and non-gymnasts (15). At enrollment, all participants (n=122) were aged 7â&#x20AC;&#x201C;12 years and nongymnasts were selected to match gymnasts for age and body size. Nongymnasts were recruited from local grade schools, whereas gymnasts were recruited from local gymnastics clubs. Prior to study initiation, institutional review board approval was provided for the study design, and written informed consent was obtained from participants and their parents.

Participants were included in the present analyses if they reported selfassessed Tanner stage I (Tanner breast I and Tanner pubic I) or Tanner stage II (Tanner breast II and Tanner pubic II) at the time of an annual DXA scan.

Non-Caucasian subjects were excluded from analyses, as there were insufficient numbers to account for racial variation. Gymnasts were included if they trained for at least 6 hours per week (hrs/wk) in the 2-year period prior to measurement, based upon a previous study (16). Following these criteria, 28 gymnasts and 28 non-gymnasts were evaluated.

All subjects attended semi-annual measurement sessions and completed questionnaires, assessing anthropometry, body composition, calcium intake and pubertal stage, as previously described (15). At these semi-annual sessions, weekly hours of organized physical activity (including gymnastics) were recorded by interview; for most gymnasts, gymnastics training was recorded in daily logs. Mean values for physical activity and calcium intake were calculated from records for the year prior to and including the focal DXA scan; these annual means were assessed as potential covariates of bone parameters. Pubertal stage and body size covariates were derived from assessments at the focal DXA session.

BONE MEASURES Fan-beam DXA scans were performed on the distal third of the left forearm using a Hologic QDR 4500W scanner (Hologic Inc., Bedford, MA) and a standardized protocol; the coefficient of variation for the machine was 1%.

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Data were included for two regions of interest (ROI) in the distal radius: the ultradistal region, composed primarily of trabecular bone and the 1/3 region, composed primarily of cortical bone (see Figure 1). Hologic software (version 9.03D) was also used to calculate non-bone, fat free mass (FFM) and percentage of body mass as fat (%BF) from whole body scans. Forearm length (cm) was measured from the tip of the ulnar styloid to the tip of the olecranon with a ruler, by the DXA technician.

Figure 1 DXA Regions of Interest for the Distal Radius: Ultradistal, Mid-distal and 1/3 Areal BMD (aBMD, g/cm2), projected area of the ROI (AreaROI, cm2), length of the ROI (LROI, mm) and BMC of the ROI (g) were assessed for the ultradistal and 1/3 regions, separately. Ratio of regional BMC/total body FFM was calculated for each ROI to evaluate regional bone mineral accumulation (BMCROI) in relation to development of total body muscle (total body FFM) and mechanical loading applied during gymnastics. Mean ultradistal and 1/3 region periosteal widths (mm) were calculated by dividing AreaROI by LROI, respectively. Results of analyses for mean periosteal width, AreaROI, and periosteal cross-sectional area were similar; only periosteal width is reported.

GEOMETRIC MODELS In order to derive measures of regional geometry and BMAD, models of simplified bone architecture were applied, as described below. Mathematical formulae are detailed in Table 1.

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Table 1 Geometric and Bone Strength Formulae Ultradistal Region In children, the ultradistal region is largely comprised of trabecular bone, with a cortical shell so thin that its depth cannot be measured accurately in vivo; therefore its assessment is simplified even in pQCT studies (21). As such, the ultradistal region was modeled as an elliptical cylinder of uniform volumetric density; “apparent” vBMD (BMAD) was calculated using the mean periosteal width and BMC of the ROI. To account for the elliptical geometry of the ultradistal radius, Sievänen et al determined that the coefficient Π approximates the general relationship between bone depth, mean periosteal width, and π (Π = 0.8); Π is used in computations of volume and/or cross-sectional area for this ROI (13). The index for structural strength in axial compressive loading, or IBS, was calculated to assess ultradistal bone strength (13). For a more detailed account, see Table 1.

1/3 region In order to derive bone architecture and strength indices, the 1/3 region of the radial shaft was treated as a hollow cylinder, with all bone mineral distributed peripherally in a shell of uniform cortical thickness and vBMD. In accordance with the narrow range of chronological age and maturational variation in our sample, calculations employed a uniform cortical vBMD of 1.01 g/cm3; this value has been reported as a pQCT–measured mean cortical vBMD for Tanner II girls at the 65% region of the radial shaft (22).

Furthermore, 1/3 cortical vBMD was assumed to be uniform across activity groups, based upon a pQCT study in which cortical vBMD did not differ between female competitive weightlifters and controls (3). Thus, our simplified model of the 1/3 radial shaft holds that: “periosteal width” is equal to “periosteal depth”; cortical vBMD is constant and equal to 1.01 36

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g/cm3; thickness of the cortical shell is uniform; and all of the bone mineral mass is distributed within the cortical shell.

On this basis, we derived variables for the 1/3 region based upon the formulae of Sievänen et al (13). To assess the cortical shell, cortical wall thickness (CWT) and cortical compartment cross-sectional area were calculated. Intramedullary diameter was derived to assess cortical shell position, relative to the centroid. To assess bone strength in response to torsion and bending forces, we derived two related indices: section modulus (Z) and cross-sectional moment of inertia (CSMI), respectively. For a true cylinder, polar moment of inertia equals 2 × CSMI and indicates torsional strength (23). As results are similar, we report only section modulus.

Calculations relied upon the equations of Sievänen et al and DXA-measured values for BMC, AreaROI, LROI and calculated mean periosteal width (W) (See Table 1)(13).

Fall Strength Ratios To assess bone strength relative to forces generated by a low trauma fall, we calculated a ratio of bone strength vs. the product of total body weight and a moment arm (weight × forearm length) (24–25). These ratios are described in the literature as “strength/weight ratios”, but we refer to them as “fall strength ratios”, to avoid confusion (24). Fall strength ratios were calculated using IBS for the ultradistal region and Z for the 1/3 region.

STATISTICAL ANALYSIS The cohort was divided into subgroups based upon maturity level (Tanner I and Tanner II) and activity status (gymnasts and non-gymnasts).

Comparisons were made between gymnasts and non-gymnasts within each maturity level. Analyses of variance (ANOVA) were used to test for significant differences between activity groups in age, body size and calcium intake, setting two-tailed alpha equal to 0.05. Site-specific, between-group differences in ratios of total body FFM/BMC and fall strength ratios were also assessed by ANOVA. For bone geometry, mass, density and strength variables, analyses of covariance (ANCOVA) were performed to adjust for age and height. Means, standard deviations, and significance levels (pvalues) are reported for ANOVA comparisons of subject characteristics. For ANOVA and ANCOVA results, means, 95% confidence intervals and significance levels are reported.

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Separate Pearson correlations for gymnasts and non-gymnasts assessed the association between dependent variables and age, body size, physical activity and calcium intake. For significant correlations between outcome variables and calcium intake or physical activity level, partial correlations were performed to adjust for the effects of age and height. Significant correlation coefficients and p-values are noted.

Go to: RESULTS As previously reported in this cohort, gymnasts and non-gymnasts did not differ significantly in age, height, weight, FFM or calcium intake within either maturity group, although Tanner I non-gymnasts exhibited higher mean %BF than Tanner I gymnasts (Table 1)(15). Gymnastics participation (hrs/wk) was significantly higher in Tanner II than Tanner I gymnasts.

Based upon exclusion criteria, all gymnasts had been participating in gymnastics for a minimum of two years at greater than 6 hrs/wk. Nongymnasts performed a wide range of organized physical activities, at variable doses (hrs/week). All non-gymnasts with at least 5.0 hrs/wk of weight-bearing activity played basketball; many also participated in other activities, including soccer, lacrosse and dance.

Ultradistal Region Tanner I gymnasts demonstrated significantly higher values than nongymnasts for all bone outcomes, with differences persisting after ANCOVA adjustment for age and height (Table 2, Figure 2a). Similarly, Tanner II gymnasts exhibited higher means for all bone measures, although periosteal width did not achieve statistical significance (p<0.08). In addition, BMC/FFM and fall strength ratios were significantly higher among gymnasts than non-gymnasts (Figures 3a, 3b).

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Table 2 Bone Parameters

Figure 2 Percentage differences are depicted for bone parameters of gymnasts relative to non-gymnasts, divided by Tanner stage and bone site: a) ultradistal region; b) 1/3 region; c) 1/3 region internal bone geometry. Bars represent 95% confidence intervals.

Figure 3 Ratios of BMC/FFM and fall strength are depicted as means with 95% confidence intervals for gymnasts (Gym) and non-gymnasts (Non-Gym), separated by Tanner stage and bone site: a) BMC/FFM; b) Z fall strength and IBS fall strength.

1/3 Region After ANCOVA adjustment for age and height, Tanner I gymnasts demonstrated significantly higher adjusted means than non-gymnasts for all bone outcomes, except intramedullary width (p<0.07) and BMAD (Table 2; Figures 2b, 2c). Tanner II results were similar, except that differences in cortical wall thickness were not significant (p<0.07). For both maturity groups, BMC/FFM and bone fall strength ratios were significantly higher in gymnasts than non-gymnasts (Figures 3a, 3b). Means for BMC/FFM ratios were consistent within activity groups, across maturity levels.

Go to: CORRELATION RESULTS 39

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FFM At both sites, gymnast FFM was uncorrelated with BMAD (p>0.28). A strong trend of positive correlation was found between FFM and 1/3 intramedullary diameter in gymnasts (R=+0.37, p=0.055). All other bone measures and derived indices were positively correlated with FFM in gymnasts (R≥+0.38 to +0.76, p<0.05).

For non-gymnasts, correlation results were similar, with two exceptions: FFM was NEGATIVELY correlated with ultradistal BMAD (R=−0.45, p<0.02) and the positive correlation with cortical wall thickness did not achieve statistical significance (R=+0.35, p=0.06).

Height Gymnasts demonstrated results for height correlations that were virtually identical in magnitude and direction to those for FFM, except that 1/3 intramedullary diameter was not correlated with height (p>0.30).

In non-gymnasts, height was a less potent correlate of bone variables than FFM; the only significant height correlates were: ultradistal mean periosteal width (R=+0.63, p=0.000), ultradistal BMC (R=+0.59, p=0.001), 1/3 aBMD (R=+0.44, p<0.05) and 1/3 CWT (R=+0.42, p<0.03). Strong trends were demonstrated for correlation of non-gymnasts‟ height vs. ultradistal aBMD, ultradistal IBS, 1/3 BMC and 1/3 cortical cross-sectional area (all R>+0.36, p<0.11). At the ultradistal site, non-gymnast BMAD demonstrated a very strong trend toward an inverse relationship with height (R= −0.31, p=0.05).

Age In general, age was the least potent correlate of bone outcome variables. For gymnasts, all bone variables were positively correlated with age (R=+0.45, p<0.02), except BMAD and intramedullary width. In contrast, for nongymnasts, only ultradistal BMC and periosteal width were positively correlated with age (R>+0.50, p<0.01).

Physical Activity Among the gymnasts, gymnastic activity (hrs/wk) was significantly, positively correlated with total forearm aBMD and all ultradistal measures except for BMAD. Gymnastics activity was significantly, positively 41

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correlated with all 1/3 measures, except for cortical wall thickness (R=+0.24, p<0.11), cortical compartment cross-sectional area (R=+0.36, p=0.06) and BMAD (no correlation). However, none of these correlations remained statistically significant after adjustment for age and height by partial correlation, although Z and periosteal width demonstrated strong trends (R=+0.39, p=0.05; R=+0.36, p<0.07).

In non-gymnasts, organized weight-bearing physical activity (hrs/wk) was not significantly correlated with any bone measure except for ultradistal BMAD (R= +0.44, p<0.02), for which height and FFM suggested inverse relationships. After adjustment for age and height, the partial correlation between physical activity and ultradistal BMAD remained statistically significant (R= +0.52, p< 0.01).

Diet Calcium intake was not significantly correlated with any forearm measure, although a strong trend was demonstrated for negative correlation between ultradistal BMAD and calcium intake among non-gymnasts (R=â&#x2C6;&#x2019;0.34, p<0.08). This relationship was not reflected by any correlation between calcium intake and ultradistal BMC, nor was there any correlation between calcium intake and any bone variable among gymnasts.

Go to: DISCUSSION In this cohort of premenarcheal females, mechanical loading was associated with dramatic adaptations in bone strength indices. At the diaphysis, these adaptations were a function of larger bone geometry; volumetric apparent density was not elevated at this site. In contrast, at the metaphysis, greater bone strength in gymnasts was primarily a function of higher volumetric apparent density (BMAD); although for Tanner I gymnasts, larger geometry also contributed to ultradistal bone strength.

These site-specific adaptations may be attributable to differences in force application and bone composition at the 1/3 and ultradistal sites. At the diaphysis, cortical bone and bending forces predominate (3). Peripheral distribution of bone mass in an enlarged cortical shell provides the most efficient resistance to bending forces (3â&#x20AC;&#x201C;4). Accordingly, gymnasts in the current study demonstrated greater 1/3 periosteal width and cortical cross41

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sectional area compared to non-gymnasts, indicating higher levels of periosteal apposition in response to mechanical loading. In contrast, at the primarily trabecular ultradistal site, bone is highly metabolically active and responsive to fluctuations in levels of circulating sex hormones. Wide, dense trabecular structure optimizes resistance to axial compressive forces that predominate at this location (3–4). Correspondingly, in the present study, gymnasts‟ ultradistal bone strength is higher than non-gymnasts due to a combination of greater volumetric apparent density and bone width.

In gymnasts, elevated BMC levels indicate that mechanical loading enhances bone accrual via weight-bearing and impact loading. At both sites, adjusted BMC was augmented and the ratio of regional BMC/total body FFM was higher in gymnasts than in non-gymnasts. The magnitude of these differentials was dictated by bone site; gymnasts demonstrated advantages of 17.5 to 20% at the 1/3 region and 26.7 to 34.5% at the ultradistal region. The larger ultradistal differential suggests that adaptation to loading requires more bone mass at this metaphyseal site. This is not surprising, given that metaphyseal resistance to axial compression requires both high total bone density and CSA, whereas diaphyseal resistance to bending forces may be improved in a more efficient manner, through peripheral distribution of bone mass.

Observed differentials in BMD, BMC and geometry are amplified when considered in biomechanical terms; strength formulae multiply and exponentiate geometric and densitometric terms, exaggerating differences (see Table 1). In the current study, strength indices demonstrated 24–38% higher diaphyseal strength (Z) and 41–56% higher metaphyseal strength (IBS) in gymnasts than non-gymnasts. These gymnastics-related strength benefits are greater than the Z differential reported for sexual dimorphism in Tanner I children and similar to sexual dimorphism in Tanner II children (26).

Strength indices were calculated using DXA-measured BMC, and derived assessments of bone geometry and density. For example, at the ultradistal radius, IBS assesses bone strength using the square of BMAD and bone width, exponentially increasing the raw values. At the diaphysis, Z is related to the cubic function of bone width (in our case, derived from projected area) and amplifies width differences accordingly. Similarly, strength-strain index (SSI- the standard pQCT bone strength assessment) accentuates geometric differences by incorporating the vBMD of each pQCT voxel into 42

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the formula for Z (26). Between-group comparisons of SSI are analogous to comparisons of Z, if equivalent cortical vBMD is assumed; this simplification is supported by Ward et al (11), who did not identify significant differences in mean cortical vBMD between pre-pubertal gymnasts and non-gymnasts.

Fall strength indices were substantially higher in gymnasts than nongymnasts at both sites. At the 1/3 region, activity group differentials were considerable (Tanner I gymnast advantage = 59.4%; Tanner II gymnast advantage = 34.3%), despite longer forearms in Tanner II gymnasts (forearm length is a factor in the ratio denominator). These advantages were even greater at the ultradistal region (Tanner I gymnast advantage= 45.3%, Tanner II gymnast advantage=61.6%). In this age range, at the ultradistal site, risk of low trauma fractures is high (24), and high fracture risk has been associated with “asynchrony” between linear growth velocity and bone mineral accrual (24). These fall strength index comparisons highlight the enhancement of bone strength attributable to loading, and support the theory that localized weight-bearing and/or impact activity may reduce risk of low trauma forearm fractures in this maturity range.

Previous investigators have provided evidence of a transient reduction in BMD related to high rates of linear growth during early puberty, suggesting asynchrony between linear growth and bone mass accumulation (28, 29).

Specifically, a pronounced lag has been demonstrated for arm BMC peak velocity relative to height and total body FFM peak velocities (30). Thus, although FFM and height are typically strong predictors of BMD and BMC (due to parallel growth rates), the relationship uncouples during this phase of asynchrony. In the present analysis, non-gymnast ultradistal BMAD was negatively correlated with total body FFM, with a similar trend for height; this would be expected during a lag in BMC accrual. In contrast, gymnast ultradistal BMAD did not correlate negatively with height or FFM, suggesting that high levels of weight-bearing/impact activity may alleviate asynchrony between linear growth and bone mass accumulation at this site.

Furthermore, non-gymnast ultradistal BMAD was positively correlated with hours per week of weight-bearing physical activity, corroborating the results of prior studies indicating that other weight-bearing activities may be associated with skeletal benefits (2, 6–7).

In a recent study, Ward et al used pQCT to assess the radius, comparing Tanner I gymnasts to non-gymnasts (aged 5.4–11.9 years) and analyzing 43

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males and females together (11). These comparisons yielded similar sitespecific differences to those found in our Tanner I girls. In the radial diaphysis, total bone CSA and cortical CSA were higher in gymnasts than non-gymnasts for both studies, although percentage differences were of higher magnitude for our cohort. In our analyses, cortical wall thickness was elevated in female gymnasts compared to non-gymnasts, but Ward et al only found a significant differential in males. Finally, diaphyseal strength was greater for gymnasts than non-gymnasts in both studies. Our differential was four times greater than that reported by Ward et al (11), this may be due to examination of a different diaphyseal site (50% vs. 1/3).

At the ultradistal radius, Ward et al‟s gymnasts exhibited higher total bone vBMD than non-gymnasts, similar to our own finding of higher apparent vBMD at this site. However, in contrast to our findings, Ward et al found no activity-related differences in total bone cross-sectional area at the ultradistal radius. Differences in the methodologies used to assess periosteal dimensions may explain the discordance between studies for metaphyseal comparisons. Our assessment of periosteal width is derived by dividing projected area by length of the ROI; this two-dimensional measure fails to account for variation in bone depth. As a result, if bone shape or aspect ratio (width vs. depth) differs substantially between subjects and/or systematically by activity group, then our bone width comparisons provide an incomplete assessment of bone geometry. In this case, failure to account for bone depth would yield different results from pQCT-measured total cross-sectional area, which assesses width, depth and shape.

In addition, our mean periosteal width reflects bone dimensions along the entire ROI, extending from approximately 5% to 12% of the ulna length (proximal to an ARTICULAR reference). In contrast, Ward et al used pQCT to measure cross-sectional area for a discrete 2 mm section of bone at 4% of the ulna length (proximal to a PHYSEAL reference). Our ultradistal ROI includes Ward et al‟s pQCT site, but the majority of the ROI extends proximally from the pQCT site. Inclusion of proximal bone may account for the greater metaphyseal width demonstrated by gymnasts in our study, particularly if this proximal region is a more sensitive barometer of geometric change. This possibility is supported by findings from a study of female tennis players, where greater side-to-side percentage differences in bone area were demonstrated in the “mid-distal” region than at both ultradistal and 1/3 regions (5). The potentially hyper-responsive mid-distal 44

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region is contiguous with the proximal zone of our ultradistal ROI (see Figure 1).

Finally, Ward‟s cohort included male subjects who were not equally represented in the two activity groups, over-representing males among nongymnasts and females among gymnasts. This unbalanced inclusion of males may have reduced the magnitude and significance of all of Ward‟s comparisons, as many of their analyses indicated smaller magnitudes for activity effects among males. Furthermore, other studies have reported sexual dimorphism in bone strength and other bone indices among prepubertal children (26, 27). Nevertheless, considering methodological differences, our results appear to complement and corroborate the pQCT findings of Ward et al.

Other studies have evaluated site-specific responses to loading, in the context of a racquet sports model. Several comparisons report side-to-side differences in the arms of adult players who began participation during childhood (1, 4, 5). Kontulainen et al used pQCT to assess the 50% humeral shaft site and the 4% distal radius site in women who began their sport at or before menarche (4). Greater side-to-side differences in BMC, total bone CSA, medullary cavity and cortical shell dimensions contributed to greater torsional Bone Strength Index at the humeral shaft for players compared to controls. In contrast, at the ultradistal radius, players exhibited a significant difference in total bone CSA between dominant and non-dominant arms, but this was not significantly greater than side-to-side differences observed in controls. Both BMC and trabecular density side-to-side percentage differences were significantly higher in players than controls at the ultradistal radius (4).

In a pQCT study of adult males, Haapasalo et al found greater total bone CSA in the dominant vs. non-dominant ultradistal radius, yet this difference was not significantly greater than the side-to-side percentage difference for controls (1). In contrast, BMC, total bone CSA, cortical CSA, and indices of bone strength all demonstrated greater side-to-side percentage differences for players vs. controls at the 30% radius and 50% humerus diaphyseal sites.

Ducher et al used DXA to evaluate side-to-side differences in aBMD and bone area, comparing tennis players and non-players (adult males and females). Percentage differences were greater for bone projected area than aBMD at the radial shaft (“mid-distal” and 1/3 regions), whereas aBMD 45

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differences were greater than bone projected area differences at the ultradistal region (5).

Although these studies of adult racquet sport participants do not directly compare players to controls, the side-to-side comparisons provide evidence of geometric response to loading at both diaphyseal and metaphyseal sites (1, 4, 5). Loading adaptations appear to emphasize geometry at the diaphysis and volumetric density at the metaphysis, as in our study.

In pre-pubertal female tennis players, Bass et al used MRI and DXA to assess side-to-side differences in humerus geometry and strength (12). At mid-shaft (50–60%) and distal (30–40%) humerus sites, significant side-toside differences were demonstrated for total bone CSA and cortical compartment CSA. Intramedullary cavity CSA was significantly higher at the dominant mid-humerus, but not at the distal humerus for Tanner I girls.

Significant side-to-side differences in polar moment of inertia (Ip, mm4) were identified for the 50% and 30–40% distal humeral shaft sites. These intrasubject comparisons at two diaphyseal humerus sites yielded lower percentage differences than our gymnast vs. non-gymnast analyses at the diaphyseal (1/3) radius; several factors may be responsible for this lower magnitude. First, loading adaptations were not evaluated at the same site.

Bass et al assessed the humerus, whereas our work assessed the radius; these sites may exhibit different responses to loading. Second, it is likely that tennis and gymnastics apply loads at different magnitudes and in different directions. Finally, Bass et al‟s side-to-side study design controls for interindividual genetic variation, potentially obliterating interactions that may amplify responses to mechanical loading. Qualitatively, Bass et al‟s findings are similar to ours, providing evidence that mechanical loading stimulates increased diaphyseal bone strength through enlarged total bone and cortical dimensions during growth.

Limitations In general, fan beam DXA-derived measures of bone geometry, BMC and aBMD are subject to magnification error that varies by distance of the region of interest from the X-ray source (14). This error is particularly influential in comparisons involving different body sizes, where considerable variation in size of the soft-tissue envelope can result in large differences in distance of the ROI from the X-ray source. Because the distal forearm demonstrates negligible intra- and inter-subject variability in soft tissue envelope size, 46

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DXA-measured BMC, projected area and aBMD are reliable (14), providing accurate information for geometric and strength derivations.

Many of our analyses rely upon simplified geometric assumptions for derivations of bone geometry and strength indices (13). These bone assessments are based upon 2-dimensional measurements that do not account for bone depth out of the DXA plane or other variations in the 3dimensional structure of the bone (31). Certainly, this methodology does not comprehensively assess complex bone architecture.

At the diaphysis, we relied upon a geometric model that assumes uniform peripheral distribution of bone to derive intramedullary and cortical compartment values from measured periosteal width and BMC. Our results yielded pronounced differences in cortical cross-sectional area for gymnasts compared to non-gymnasts, whereas intramedullary diameter differences were not demonstrated. These findings mirror the results of side-to-side comparisons in loaded vs. non-loaded arms of Tanner I, female tennis players; in this previously cited MRI study of the 30â&#x20AC;&#x201C;40% distal humerus, significant differences were identified for cortical CSA and periosteal CSA, but not for intramedullary diameter (12). A similar pattern was reported by Ward et al for Tanner I gymnast vs. non-gymnast comparisons at the 50% radius (11). Concordance of our results with results from these 3dimensional bone analyses supports the use of a simplified geometric model to interpret DXA data for the growing radius (11, 12). In addition, our derivations assume a uniform cortical vBMD of 1.01 g/cm3 for all gymnasts and non-gymnasts, supported by the results of Ward et al (11). Nonetheless, it should be noted that the validity of our results would be marred in the event of an activity-related cortical vBMD differential.

Thus, although the diaphysis is not truly a perfect hollow cylinder, use of Sievanenâ&#x20AC;&#x;s simplified model provides similar results to MRI and pQCT evaluations in this age group (11, 12). Future studies should directly assess the validity of this methodology, through analysis of contemporaneous DXA and pQCT scans in the context of physical activity, age and maturational variation; DXA-derivations and models should be compared to pQCT output for bone geometry, strength indices and compartmental vBMD. Finally, gymnasts demonstrated elevated ultradistal BMAD, analogous to high total bone vBMD. Our DXA-derived methods cannot discern whether this higher apparent density is a function of increased trabecular volumetric 47

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density, increased cortical shell thickness, or a combination of the two.

These properties must be specifically addressed using pQCT and/or microQCT to isolate the adaptation of cortical and trabecular structure to mechanical loading, accounting for male-female differences (32).

Conclusion Bone response to mechanical loading is exhibited through site-specific variation in volumetric and geometric properties. Adaptation to weightbearing/impact activity is dominated by elevated BMAD at the ultradistal radius and by larger bone geometry in the 1/3 region. Both ultradistal and 1/3 sites exhibit significant bone mass and strength benefits that are attributable to impact/weight-bearing stimulation in these premenarcheal girls. Thus, in this cohort, significant site-specific advantages in bone mass, strength and geometry underlie the areal BMD benefit associated with physical activity.

Go to: Acknowledgments The authors are grateful to the subjects and their parents; without their effort and commitment, this study would not have been possible. We also acknowledge our study coordinator, Susan Hemingway and current and former colleagues: Robert Ploutz-Snyder, Jill Kanaley, Kay Bruening, Jacqueline Cole, James DiStefano, Moira Davenport, Nicole Gero, Michael Mincolla, Christina Morganti, and Marjolein van der Meulen. This project was funded by grants from the Orthopedic Research and Education Foundation and from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Funding Sources: NIH/NIAMS (#AR47613) and Orthopedic Research and Education Foundation (#97-015) Go to: Footnotes Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo 48

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copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Go to: References 1. Haapasalo H, Kontulainen S, Sievänen H, Kannus P, Jarvinen M, Vuori I. Exercise-induced bone gain is due to enlargement in bone size without a change in volumetric bone density: A peripheral quantitative computed tomography study of the upper arms of male tennis players. Bone.

2000;27:351–357.[PubMed] 2. Duncan CS, Blimkie CJR, Kemp A, et al. Mid-femur geometry and biomechanical properties in 15- to 18-yr-old female athletes. Med Sci Sports Exer. 2002;34:673–681.

3. Heinonen A, Sievänen H, Kannus P, Oja P, Vuori I. Site-specific skeletal response to long-term weight training seems to be attributable to principal loading modality: a pQCT study of female weightlifters. Calcif Tissue Int. 2002;70:469–474.[PubMed] 4. Kontulainen S, Sievänen H, Kannus P, Pasanen M, Vuori I. Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: A peripheral quantitative computed tomography study between young and old starters and controls. J Bone Miner Res. 2003;18:352–359.[PubMed] 5. Ducher G, Prouteau S, Courteix D, Benhamou C-L, et al. Cortical and trabecular bone at the forearm show different adaptation patterns in response to tennis playing. J Clin Densitom. 2004;7:399–405.[PubMed] 6. Nikander R, Sievänen H, Heinonen A, Kannus P. Femoral neck structure in adult female athletes subjected to different loading modalities. J Bone Miner Res. 2005;20:520–528.[PubMed] 7. Nikander R, Sievänen H, Uusi-Rasi K, Heinonen A, Kannus P. Loading modalities and bone structures at nonweight-bearing upper extremity and weight-bearing lower extremity: A pQCT study of adult female athletes.

Bone. 2006 doi: 10.1016/j.bone.2006.04.005. in press; Available online 5/30/2006. [Cross Ref] 8. Dyson K, Blimkie CJR, Davison KS, Webber CE, Adachi JD. Gymnastic training and bone density in pre-adolescent females. Med Sci Sports Exerc.

1997;29:443–450.[PubMed] 49

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9. Faulkner RA, Forwood MR, Beck TJ, Mafukidze JC, Russell K, Wallace W. Strength Indices of the Proximal Femur and Shaft in Prepubertal Female Gymnasts. Med Sci, Sports Exerc. 2003;35:513–518.[PubMed] 10. Nanyan P, Prouteau S, Jaffre C, Benhamou L, Courteix D. Thicker radial cortex in physically active prepubertal girls compared to controls. Int J Sports Med. 2005;26:110–115.[PubMed] 11. Ward KA, Roberts SA, Adams JE, Mughal MZ. Bone geometry and density in the skeleton of pre-pubertal gymnasts and school children. Bone.

2005;36:1012–1018.[PubMed] 12. Bass SL, Saxon L, Daly RM, et al. The effect of mechanical loading on the size and shape of bone in pre-, peri-, and post-pubertal girls: A study in tennis players. J Bone Miner Res. 2002;17:2274–2280.[PubMed] 13. Sievänen H, Kannus P, Nieminen V, Heinonen A, Oja P, Vuori I. Estimation of various mechanical characteristics of human bones using dual energy x-ray absorptiometry: methodology and precision. Bone.

1996;18:17S–27S.[PubMed] 14. Cole JH, Scerpella TA, van der Meulen MCH. Fan-beam densitometry of the growing skeleton: are we measuring what we think we are? J Clin Densitom. 2005;8:57–64.[PubMed] 15. Dowthwaite JN, DiStefano JG, Ploutz-Snyder RJ, Kanaley JA, Scerpella TA. Maturation and Activity-Related Differences in Bone Mineral Density: Tanner I vs. Tanner II and Gymnasts vs. Non-Gymnasts. Bone. 2006 doi: 10.1016/j.bone.2006.04.007. In press, available online 6/6/2006. [Cross Ref] 16. Scerpella TA, Davenport M, Morganti CM, Kanaley JA, Johnson LM. Dose related association of impact activity and bone mineral density in prepubertal girls. Calcif Tiss Int. 2003;72:24–31.

17. Gero N, Cole J, Kanaley J, van der Meulen J, Scerpella T. Increased bone accrual in premenarcheal gymnasts: A longitudinal study. Ped Ex Sci. 2005;17:43–55.

18. Nurmi-Lawton JA, Baxter-Jones AS, Mirwald RL, et al. Evidence of sustained skeletal benefits from impact-loading exercise in young females: a 3-year longitudinal study. J Bone Miner Res. 2004;19:314–322.[PubMed] 19. Bass S, Pearce G, Bradney M, et al. Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts. J Bone Miner Res. 1998;13:500–507.[PubMed] 20. Kudlac J, Nichols DL, Sanborn CF, DiMarco NM. Impact of Detraining on Bone Loss in Former Collegiate Female Gymnasts. Calcif Tissue Int. 2004;75:482–487.[PubMed]

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21. Rauch F, Schönau E. Peripheral quantitative computed tomography of the distal radius in young subjects- new reference data and interpretation of results. J Musculoskelet Neuronal Int. 2005;5(2):119–126.

22. Schoenau E, Neu CM, Rauch F, Manz F. Gender-specific pubertal changes in volumetric cortical bone mineral density at the proximal radius.

Bone. 2002;31:110–113.[PubMed] 23. Petit MA, Beck TJ, Kontulainen SA. Examining the developing bone: What do we measure and how do we do it? J Musculoskelet Neuronal Interact. 2005;5:213–224.[PubMed] 24. Rauch F, Neu C, Manz F, Schoenau E. The development of metaphyseal cortex- Implications for distal radius fractures during growth. J Bone Miner Res. 2001;16:1547–1555.[PubMed] 25. Ruff C. Growth tracking of femoral and humeral strength from infancy through late adolescence. Acta Paediatrica. 2005;94:1030–1037.[PubMed] 26. Schoenau E, Neu CM, Rauch F, Manz F. The development of bone strength at the proximal radius during childhood and adolescence. J Clin Endocrinol Metab. 2001;86:613–618.[PubMed] 27. MacDonald H, Kontulainen S, Petit M, Janssen P, McKay H. Bone strength and its determinants in pre- and early pubertal boys and girls. Bone.

2006 doi: 10.1016/j.bone.2006.02.057. In press, available online 4/4/2006.

[Cross Ref] 28. Fournier P-E, Rizzoli R, Slosman D-O, Theintz G, Bonjour J-P. “asynchrony” between the rates of standing height gain and bone mass accumulation during puberty. Osteoporos Int. 1997;7:525–532.[PubMed] 29. McKay HA, Bailey DA, Mirwald RL, Davison KS, Faulkner RA. Peak bone mineral accrual and age at menarche in adolescent girls: a 6-year longitudinal study. J Pediatr. 1998;133:682–687.[PubMed] 30. Rauch F, Bailey DA, Baxter-Jones A, Mirwald R, Faulkner R. The „muscle-bone unit‟ during the pubertal growth spurt. Bone. 2004;34:771– 775.[PubMed] 31. Bass SL. The structural adaptations of cortical bone to loading during different stages of maturation. J Musculoskel Neuron Interact. 2003;3:345– 347.

32. Khosla S, Riggs BL, Atkinson EJ, et al. Effects of sex and age on bone microstructure at the ultradistal radius: A population-based noninvasive in vivo assessment. J Bone Miner Res. 2006;21:124–131. [PMC free article][PubMed]

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Do team gymnasts compete in spite of symptoms from an injury?

M Harringe, S Lindblad, and S Werner Author information â&#x2013;ş Copyright and License information â&#x2013;ş Abstract Background: Gymnasts practise many hours a week, and symptoms from injuries do not seem to stop them from continuing with practice. They may even compete with symptoms from injuries, which could increase the risk of reinjury, or of the occurrence of a more severe injury.

Objectives: To investigate whether team gymnasts compete at high level in spite of symptoms from an injury.

Methods: 188 male and female competitors participating in the Swedish Cup for juniors and seniors answered a questionnaire about symptoms from injuries on the day of the competition.

Results: More than half the gymnasts (58%) competed despite having symptoms from an injury on the day of the competition. More seniors than juniors competed in spite of symptoms from an injury (p = 0.006). Two of three team gymnasts (65%) reported symptoms from the lower extremities and around one in five (22%) reported back symptoms. Fifty five per cent of the gymnasts reported recurrence of an injury at the same site (reinjury).

Conclusions: There was a high prevalence of symptoms from injuries on the day of competition. This did not stop the team gymnasts from competing.

Full Text The Full Text of this article is available as a PDF (99K).

Selected References These references are in PubMed. This may not be the complete list of references from this article.

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Caine D, Cochrane B, Caine C, Zemper E. An epidemiologic investigation of injuries affecting young competitive female gymnasts.

Am J Sports Med. 1989 Nov-Dec;17(6):811–820.[PubMed] Garrick JG, Lewis SL. Career hazards for the dancer. Occup Med. 2001 Oct-Dec;16(4):609–iv.[PubMed] Sands WA, Shultz BB, Newman AP. Women's gymnastics injuries. A 5-year study. Am J Sports Med. 1993 Mar-Apr;21(2):271– 276.[PubMed] Bowling A. Injuries to dancers: prevalence, treatment, and perceptions of causes. BMJ. 1989 Mar 18;298(6675):731–734. [PMC free article][PubMed] Kolt GS, Kirkby RJ. Epidemiology of injury in elite and subelite female gymnasts: a comparison of retrospective and prospective findings. Br J Sports Med. 1999 Oct;33(5):312–318. [PMC free article][PubMed] Jørgensen U, Bojsen-Møller F. Shock absorbency of factors in the shoe/heel interaction--with special focus on role of the heel pad. Foot Ankle. 1989 Jun;9(6):294–299.[PubMed] Dixon M, Fricker P. Injuries to elite gymnasts over 10 yr. Med Sci Sports Exerc. 1993 Dec;25(12):1322–1329.[PubMed] Eriksson K, Németh G, Eriksson E. Low back pain in elite crosscountry skiers. A retrospective epidemiological study. Scand J Med Sci Sports. 1996 Feb;6(1):31–35.[PubMed] Kujala UM, Taimela S, Erkintalo M, Salminen JJ, Kaprio J. Low-back pain in adolescent athletes. Med Sci Sports Exerc. 1996 Feb;28(2):165–170.[PubMed] Swärd L, Hellström M, Jacobsson B, Nyman R, Peterson L. Disc degeneration and associated abnormalities of the spine in elite gymnasts. A magnetic resonance imaging study. Spine (Phila Pa 1976) 1991 Apr;16(4):437–443.[PubMed] Fridén C, Hirschberg AL, Saartok T, Bäckström T, Leanderson J, Renström P. The influence of premenstrual symptoms on postural balance and kinesthesia during the menstrual cycle. Gynecol Endocrinol. 2003 Dec;17(6):433–439.[PubMed] Arokoski JP, Kankaanpä M, Valta T, Juvonen I, Partanen J, Taimela S, Lindgren KA, Airaksinen O. Back and hip extensor muscle function during therapeutic exercises. Arch Phys Med Rehabil. 1999 Jul;80(7):842–850.[PubMed]

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Lipid Gymnastics: Evidence of Complete Acyl Chain Reversal in Oxidized Phospholipids from Molecular Simulations Himanshu Khandelia and Ole G. Mouritsen Author information ► Article notes ► Copyright and License information ► This article has been cited by other articles in PMC. Go to: Abstract In oxidative environments, biomembranes contain oxidized lipids with short, polar acyl chains. Two stable lipid oxidation products are PoxnoPC and PazePC. PoxnoPC has a carbonyl group, and PazePC has an anionic carboxyl group pendant at the end of the short, oxidized acyl chain. We have used MD simulations to explore the possibility of complete chain reversal in OXPLs in POPC-OXPL mixtures. The polar AZ chain of PazePC undergoes chain reversal without compromising the lipid bilayer integrity at concentrations up to 25% OXPL, and the carboxyl group points into the aqueous phase. Counterintuitively, the perturbation of overall membrane structural and dynamic properties is stronger for PoxnoPC than for PazePC. This is because of the overall condensing and ordering effect of sodium ions bound strongly to the lipids in the PazePC simulations. The reorientation of AZ chain is similar for two different lipid force fields. This work provides the first molecular evidence of the “extended lipid conformation” in phospholipid membranes. The chain reversal of PazePC lipids decorates the membrane interface with reactive, negatively charged functional groups.

Such chain reversal is likely to exert a profound influence on the structure and dynamics of biological membranes, and on membrane-associated biological processes.

Abbreviations: AZ, azelaoyl; DLPC, dilinoleoyl phosphatidylcholine; HazPC, 1-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocholine; LDL, lowdensity lipoprotein; MD, molecular dynamics; OX, oxo-nonanoyl; OXPLs, oxidized phospholipids; PazePC, 1-palmitoyl-2-azelaoyl-ns-glycero-3phosphocholine; PLPC, 1-palmitoyl-2-linoleoyl-sn-glycero-3phosphatidylcholine; PME, particle mesh Ewald; POPC, 1-palmitoyl-2-

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oleoyl-sn-glycero-3-phosphocholine; PoxnoPC, 1-palmitoyl-2-(9â&#x20AC;˛-oxononanoyl)-sn-glycero-3-phosphocholine Go to: Introduction Mammalian phospholipids have mostly monounsaturated or polyunsaturated acyl chains (1). Unsaturated phospholipids are prone to oxidation at the location of the carbon-carbon double bonds. Phospholipid oxidation can be enzyme mediated or can result from reaction of lipids with reactive oxygen species including free radicals present in various tissues (2). Lipid oxidation products can bind receptors (3) and proteins, and influence signaling processes (2). Furthermore, owing to an atypical lipid structure (shorter and more polar acyl chains), OXPLs are expected to alter the physical properties of the lipid bilayer membrane, the effects of which can cascade down to several essential cellular processes. For example, lipid oxidation products can trigger mitochondrial damage (4) and have been implicated in mediating several diseased states, including cancer (5) and atherosclerosis (6).

PoxnoPC and PazePC are two stable lipid oxidation products. (Fig. 1).

PoxnoPC and PazePC are OXPLs, which bear carbonyl and carboxyl groups at the end of their truncated sn-2 chains. In aqueous solution, the carbonyl and carboxyl groups are zwitterionic and anionic, respectively, at neutral pH (7). PoxnoPC is one of the key products of ozone-mediated oxidation of lung surfactant extract and promotes apoptosis and necrosis (8). PazePC has been detected in LDL and is a weak ligand for the peroxisome proliferatoractivated receptor (3). HazPC, where the esterified acyl chains of PazePC is replaced by ether-linked alkyl residues, is also found in abundance in LDL (9) and has been implicated in the genesis of atherosclerosis. HazePC induces mitochondrial damage (4) and is a potent agonist to peroxisome proliferator-activated receptor Îł, a protein that controls metabolic and cellular differentiation genes (10). The biochemical, biophysical, and physiological characterization of PoxnoPc and PazePC has been limited in comparison to HazPC and to other peroxidized lipid products (11).

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Figure 1 POPC and its two oxidation products investigated in this work. The partial charges for the carbonyl and carboxyl carbon, as well as oxygen atoms are shown.

The properties of PazePC were investigated using force-area (Ď&#x20AC;-A) isotherms on a Langmuir balance in mixed monolayers with DPPC (12). It was proposed that the large free energy penalty of embedding a charged carboxylate moiety of the AZ in the hydrophobic core of a lipid bilayer might induce the reorientation of AZ into the aqueous phase, which would then adopt the so-called extended lipid conformation (13). Further evidence of AZ chain reversal came from measuring fluorescence resonance energy transfer as a result of the association of the water-soluble protein cytochrome c with PazePC micelles (14). The protein bound strongly to the micellar aggregates. The extent of binding reduced upon lowering pH (which would protonate the carboxylic acid on AZ) or upon addition of Ca2+ ions (which would bind competitively to the carboxylic acid group, thus inducing protein dissociation from the micelles). PoxnoPC and PazePC can be potential drug targets for antipsychotic compounds (15) and for antimicrobial peptides in cells under oxidative stress at inflammatory sites (16).

There is indirect evidence that chain reversal of the PazePC sn-2 chain might occur in PazePC monolayers (12) and in PC bilayers containing PazePC (14). Chain order parameters, density profiles, local curvature, and the electrostatic potential profiles across the bilayer are properties that might be directly affected by the presence of potentially chain-reversing charged lipids in a bilayer membrane. However, other than the preliminary evidence 56

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cited above, there have been no direct measurements of chain reversal in lipids and its impact on the properties of membranes. MD simulations have been previously used to characterize the impact of early peroxidation products of PLPC, including the carbonyl equivalent of PoxnoPC (11).

Although complete chain reversal was not observed possibly because the oxidized chains were not hydrophilic enough, some of the oxidized sn-2 chains were found to be able to reach the lipid-water interface and make hydrogen bonds with water and lipid headgroups.

In this work, we employ fully atomistic MD simulations of POPC lipid bilayers doped with various amounts of PazePC and PoxnoPC to investigate the possibility of AZ-chain reversal and characterize the impact that such chain reversal might have on the overall physical properties of the lipid bilayer. MD simulations of lipid bilayer systems are now routinely used to study model lipid bilayer membranes to obtain a molecular perspective of the structural and dynamics properties of membranes, while providing detailed microscopic interpretations of experimental measurements (11,17â&#x20AC;&#x201C; 22).

Go to: Methods The starting coordinates of a POPC bilayer were obtained from a 100 ns preequilibrated system (23), the starting structure for which was derived from coordinates available at http://moose.bio.ucalgary.ca/. Force-field parameters for POPC lipids were taken from the united atom force field of Berger et al. (24), available at http://moose.bio.ucalgary.ca/. Force-field parameters of PazePC were derived from the POPC force field, by truncating the oleoyl chain at the double bond, replacing the last carbon by a carboxyl group, and adjusting the geometry appropriately. For the carboxyl group, partial charges of amino acids were used. For the carbonyl group of PoxnoPC, the parameters were taken from previous simulations (11). The hydrogen atom of the carbonyl group was treated implicitly.

Random lipid molecules in the pure POPC bilayer were replaced with OXPLs, keeping the number of OXPLs equal in both lipid monolayers. Six different concentrations were used for both PazePC and PoxnoPC, ranging from 1/128 mol fraction OXPL to 1/4 mol fraction OXPL (Table 1). The

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total number of lipids in each system was 128. Sodium counterions were used to keep the PazePC systems electrostatically neutral.

Table 1 List of completed simulations MD simulations were carried out using the GROMACS 3.3.1 package in the isobaric-isothermal (NPT) ensemble at 1 bar and 320 K, using the Berendsen (25) thermostat (relaxation time 0.1 ps) and barostat (coupling constant 1.0) with semiisotropic pressure coupling. The Z axis was parallel to the bilayer normal. A time step of 2 fs was used, and coordinates were saved every 10 ps. The LINCS (26) algorithm was used to constrain bonds with hydrogen atoms. The PME (27) method was used to calculate long-range electrostatic interactions with a fourth-order spline and a grid spacing of 0.1. The relative error for the Ewald sum in the real and reciprocal space was set to 10−5. The short-range van der Waals and real space Coulomb interactions were cutoff at 10 Å. Periodic boundary conditions were applied in all three directions.

The Simple Point Charge model (28) was water was used.

The area per lipid (AL) in the PazePC simulations equilibrated within ~50 ns.

The simulations were carried out for more than 100 ns in each system after initial energy minimization. For calculation of ensemble averages, the first 50 ns of each simulation were discarded.

To evaluate the influence of force field and simulation ensemble (NPT versus NPzAT), simulations were also carried out using the CHARMM param27 force field for PazePC. These simulations were carried out in the NPzAT ensemble, where the area was kept constant in the XY plane to 65.5 Å2 per lipid, and only the Z dimension (along the bilayer normal) of the simulation cell was allowed to fluctuate. As a result of an oversight in the configuration files, these simulations were carried out at 313 K, instead of 320 K, which was used in the GROMACS simulations. However, the 58

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slightly lower temperature should not affect the structure of the system significantly because 313 K is still well above the main-phase transition temperature of POPC. Simulations with the CHARMM27 parameter set for lipids (29) were performed with NAMD v2.6 (30). A procedure similar to that described above for GROMACS was used to develop the force field for PazePC. The SHAKE algorithm (31) was used to constrain bonds with hydrogen atoms. A time-step of 2 fs was used, but full electrostatic calculations were computed every 4 fs. The PME method (32) was used for computation of electrostatic forces. The grid spacing was kept below 1.0 Å, and a fourth-order spline was used for interpolation. Van der Waals interactions were smoothly switched off over a distance of 4.0 Å, between 10 Å and 14 Å. The Langevin piston method (33) with a damping coefficient of 5 ps−1 and a piston period of 100 fs was used to maintain constant pressure and temperature conditions. The ratio of the cell dimensions was kept constant in the XY plane.

In total, 6 PazePC + 6 PoxnoPC + 1 pure POPC = 13 simulations were implemented in GROMACS, and 5 PazePC + 1 pure POPC = 6 simulations were implemented in CHARMM (Table 1). The simulations were run on a Linux cluster with Dell PowerEdge 2950, 2 × 2, 66 Ghz Intel Woodcrest CPUs, connected with 2× Gigabit Ethernet. The performance was ~18ns/day (4 cpus) and 3 ns/day (8 cpus) for the GROMACS and CHARMM simulations, respectively.

To resolve the effect of sodium counterions on the structure of the bilayer, an additional simulation with 25% PazePC without sodium ions was implemented. The sodium ions were replaced by a uniform neutralizing charge density, so that PME calculations could be performed.

Analysis of the GROMACS simulations were carried out in the GROMACS suite of programs, whereas the analysis of the NAMD trajectories was carried out in the CHARMM package (36). Visual Molecular Dynamics (VMD) was used for molecular graphics (37). Unless otherwise mentioned, all results discussed refer to the GROMACS simulations. Analysis of the NAMD simulations were used for force-field comparison purposes only.

Most of the following analysis and discussion focuses on the 25% OXPL systems, for which the changes in the properties of the membrane are most remarkable. OXPLs are present in various tissues at different concentrations.

Accounting for the possibility of OXPL-induced phase separation (see later 59

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discussion), it is possible that local concentrations of OXPLs in membranes can be as high 25% physiologically.

Go to: Results Chain reversal The AZ chain of PazePC lipids reoriented such that the carboxyl group pointed out into the aqueous phase (Fig. 2). The effect was more pronounced at higher concentrations of PazePC. The tilt angle (Fig. 3) was defined as the angle between the bilayer normal and the vector from the last to the first carbon atom of the oxidized sn-2 acyl chain. Even at the lowest AZ concentration, the average tilt angle was at least 90째, indicating that the AZ chain was at least parallel to the interface. At 25% PazePC, the tilt angle of the chains approached a uniform distribution peaking at 160째, indicating nearly complete chain reversal. In PoxnoPC lipids, the OX chains carrying the terminal carbonyl group also reoriented, but not to the extent of the AZ chains of PazePC. The OX chains rarely extended out of the interface, but were able to reorient to reach the lipid headgroups. The distribution of tilt angles of the OX chains is shown in Fig. 3, b.

Figure 2 Simulation snapshots of a single PazePC and PoxnoPC molecule from the 25% OXPL simulations. The images were taken at uniform intervals during the last 50 ns and superimposed. The oxidized sn-2 chains are shown in yellow, except for the terminal (more ...)

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Figure 3 The concentration-dependent tilt angle distribution of the oxidized sn-2 chains of PazePC (a) and PoxnoPC (b). The numbers in the legend refer to the number of OXPLs present in each simulation. The tilt angle was defined as the angle between the bilayer (more ...)

Fig. 4 shows the density distribution of the carboxyl and carbonyl groups in the 25% PazePC and PoxnoPC simulations, relative to the density of phosphate for the pure POPC simulation. The distribution of the carboxyl group is nearly 30 Ă&#x2026; wide in each leaflet and has two peaks: one in the aqueous phase, and the other just below the phosphate density. The carboxyl groups of some PazePC lipids were found to fluctuate between an interfacial position and a completely water-exposed conformation. However, there were some PazePC lipids for which the water-exposed conformation was not accessible, and other PazePC lipids for which the interfacial conformation was not accessible. Thus, the carboxyl groups of an individual PazePC lipid could adopt either an interfacial or aqueous conformation, or both. There was a vanishing density near the center of the bilayer. The carbonyl groups, being less hydrophilic, remained mostly confined below the phosphate interface. Radial distribution functions and hydrogen-bonding analysis indicated that the carbonyl groups of OX chains were closest to the ester region and made hydrogen bonds with both water and the esters (data not shown). The extent of reorientation of OX chains in this work is similar to that reported of OX chains in mixtures of OXPLs with PLPC bilayers (11).

Figure 4 Density distribution of carboxyl (COO-) group of PazePC and carbonyl (CHO) group of PoxnoPC for the 25% OXPL simulations. The density of the phosphate is from the pure POPC simulation and was scaled by a factor of ~0.067 to facilitate comparison. (more ...)

Area, thickness, and density

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The overall electron density of the bilayers with 25% OXPLs is shown in Fig. 5. The two main features of a higher density at the center of the bilayer, and a shift of the maxima toward the bilayer center, are in agreement with previous MD simulations of Wong-Ekkabut et al. (11) and x-ray scattering experiments on peroxidized DLPC lipid bilayers (38). In PazePC, there is also a slightly increased density in the aqueous region owing to the sn-2 chain reversal. Fig. 6 shows the average area per lipid (AL) and the thickness of the bilayers. Error estimates were calculated using a block averaging procedure (39). Interestingly, the perturbation of the electron density profile, and the overall AL and thickness is greater for PoxnoPC than for PazePC. In PoxnoPC, the sn-2 chains reorient such that the terminal carbonyl groups intercalate into the head-group region of the lipids, resulting in a higher AL and a significantly lower bilayer thickness. The lateral expansion of the bilayer with PoxnoPC is in qualitative agreement with monolayer expansion experiments of PoxnoPC and PazePC mixed with DPPC (12). The simulations thus support the model proposed by Sabatini et al. (12) that accommodation of polar moieties of the oxidized chain in the head-group region leads to expansion of the lipid monolayer. However, the simulations are in apparent conflict with the experimental observation that monolayer expansion was greater in the presence of PazePC (12). The conflict is resolved by taking into account the effect of sodium countercations in the PazePC simulation. The sodium cations were found to bind strongly to the interfacial glycerol region of the bilayer (data not shown). Interactions between the sodium cations and PC membranes result in membrane compression (18) using the Berger (24) force field for lipids.

Figure 5 The overall electron density of the pure POPC bilayer, and for POPC bilayer with 25% OXPL.

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Figure 6 Average area per lipid (a) and thickness (b) of the lipid bilayers at various concentrations of OXPL. The errors were estimated using a block-averaging approach and cannot be seen in some cases because they are smaller than the size of the symbols. The (more ...)

To better understand the effect of sodium counterions on the area and thickness of the PazePC simulations, the 25% PazePC simulation was carried out without sodium ions. The system now had a net charge of −32.

To permit use of PME, the system was kept electrostatically neutral by adding a uniform neutralizing charge density in the simulation box. In the absence of sodium ions, the area per lipid of the 25% PazePC simulation increased to 72 ± 0.52 Å2, and the bilayer thickness decreased to 32.53 ± 0.19 Å. The corresponding numbers for area and thickness for the 25% PazePC simulations in presence of sodium ions (Fig. 6) were 64.57 ± 0.32 Å2 and 36.2 ± 0.097 Å, respectively. The area and thickness for the 25% PoxnoPC simulations (Fig. 6) were 69.11 ± 0.11 Å2 and 34.60 ± 0.06 Å, respectively. Thus, in the absence of sodium ions, the PazePC-containing lipid bilayer expands as a result of chain reversal, whereas in the presence of sodium ions, the expanding effect induced by chain reversal is offset by the condensing effect of the strong binding of sodium ions to the lipid-water interface. The expansion of the bilayer was more for PazePC than for PoxnoPC, in agreement with the monolayer experiments (12). The tilt angle profiles for the AZ chain in the 25% PazePC simulations with and without sodium counterions are compared in Fig. 7. The tilt angles were unaffected by the presence of sodium, indicating that the PazePC chain reversed completely in the simulations without sodium as well.

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Figure 7 Tilt angle distribution for the AZ chain the 25% PazePC simulations, with and without salt. The definition of tilt angle is the same as in Fig. 3.

In Fig. 8, the density of the carboxyl and the phosphate groups are compared for 12.5% PazePC for the two force fields: CHARMM (param27 force field for lipids) and GROMACS (Berger force field for lipids). The comparison is not straightforward because the simulations in GROMACS were carried out in the NPT ensemble, whereas those with the CHARMM force field were carried out in the NPzAT ensemble, where the dimensions of the cell were fixed in the bilayer plane. The NPzAT ensemble was used with CHARMM, because the CHARMM force field leads to unreasonably low equilibrium values of area-per-lipid and gel-like behavior (40,41) in NPT. Nevertheless, the CHARMM simulations corroborated the two-peak chain reversal of the AZ side chain. In CHARMM, the interfacial density peaks of COO− are higher than those in GROMACS. In GROMACS, the COO− peaks are further out in the aqueous phase, and the carboxyl groups spend more time there relative to the CHARMM simulation. The complete chain-reversing effect is less pronounced in CHARMM because the area is fixed in the XY plane, and the lipid headgroups cannot freely accommodate the reverse orientation of the sn-2 AZ chain. However, there is qualitative agreement between the two force fields, and the AZ chain undergoes complete chain reversal in both cases.

Figure 8 Partial density of the carboxyl (COO−) and phosphate (PO4) groups in the 12.5% OXPL simulations with the CHARMM (CHM) and the GROMACS (GMX) force fields. The density of phosphate was scaled by a factor of 0.05 to facilitate comparison.

Order parameters The lipid chain order parameters were used to quantify the extent of chain disorder induced by the OXPLs. Order parameters were calculated as 64

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described in Wong-Ekkabut et al. (11). The order parameters for the palmitoyl chains of POPC lipids for varying concentrations of PoxnoPC and PazePC are shown in Fig. 9. Interestingly, the uncharged OX side chain induced more disorder in the bilayer compared to anionic AZ side chain. It could be envisioned that this is because the OX chains were oriented nearly perpendicular to the bilayer normal, which disturbed bilayer packing. In PazePC, on the other hand, the complete chain reversal of the AZ chains reduced the extent of disorder in the lipid bilayer. However, simulations of the sodium-free PazePC simulations suggest that the reduced disorder in PazePC-POPC compared to PoxnoPC-POPC bilayers was the result of the compression effect of tightly bound sodium counterions, which were present only in the PazePC simulations. In the 25% PazePC simulation without sodium ions, the acyl chain order of POPC lipids was lower than for 25% PazePC with sodium, and also lower than that in 25% PoxnoPC (see Fig. S1 in the Supporting Material). The overall trends were similar for the order parameters of the oleoyl chain of POPC, the results for which have not been shown.

Figure 9 The order parameters for the palmitoyl chain of POPC lipids as a function of the amount of PoxnoPC (a) and PazePC (b) present. The numbers in the legend refer to the number of OXPL present in each simulation.

Electrostatic potential The electrostatic potential profiles for the 25% PazePC and PoxnoPC are shown in Fig. 10, alongside that of a pure POPC bilayer. The electrostatic potential was calculated from the Poisson equation by a double integration of the charge density profile across the bilayer obtained from the MD simulation. Although both OXPLs were found to induce a lower dipole potential barrier near the interface compared to POPC, the effect was more pronounced for PoxnoPC than for PazePC. The distribution of the headgroup orientation (P-N) vector (drawn from the phosphorus atom to the nitrogen atom of choline) with respect to the bilayer normal did not change much for POPC lipids, even at the highest concentration of OXPLs (data not 65

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shown). PazePC lipids had a P-N distribution that peaked at 25°. However, PoxnoPC lipids had a wider P-N distribution, which peaked at 55°.

Figure 10 The electrostatic potential profile across a single monolayer for the pure POPC and the 25% OXPL simulations. The potential was calculated from double integration of Poisson's equation along the bilayer normal.

Go to: Discussion The simulations reported in this work provide direct evidence that upon sufficient oxidation of a sufficiently large number of unsaturated lipids, the orientation of oxidized acyl chains of phospholipids in lipid bilayers can reverse completely. To our knowledge, this is the first direct molecular evidence of spontaneous chain reversal of free-standing phospholipid bilayers. Chain splaying has only been observed in previous simulations in interacting bilayers (42). The enthalpic penalty of embedding a charged group in the hydrophobic core of the membrane is thus sufficiently large to offset the entropic penalty of exposing approximately seven hydrophobic methylene groups of the AZ acyl chain to the aqueous phase and the interfacial region of the bilayer.

Chain reversal of oxidized unsaturated chains presents potent reactive functional groups to the aqueous phase, in this case, an anionic carboxylic acid (COO−) moiety, the presence of which on the membrane interface can have myriad effects on the properties of integral and peripheral membrane proteins (14); on peptides; as well as on the binding of ions, drugs (15), hormones, and small antimicrobial peptides (16). The negative charge of most anionic phospholipids resides on the phosphate group. The impact of the reversed AZ chain is expected to be different from that due to the presence of conventional anionic lipids, because the COO− group of PazePC can extend into the aqueous phase up to 10 Å beyond the average plane of the phosphate groups (Fig. 4). Furthermore, the COO− group is unshielded, and being pendant on a flexible acyl chain, it can adopt a variety of 66

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conformations, depending upon the specific interaction with the ligand it binds. Depending upon the reaction enthalpy available, COO− can also participate in covalent reactions, including formation of esters (with alcohols), anhydrides (with other carboxylic acid chains), or amides (with amines). Oxidized LDL participates in the genesis of atherosclerosis (43).

Free fatty acids like oleic acid are known to react with cholesterol in oxidized LDL to form cholesteryl esters, the accumulation of which has been also associated with atherosclerosis (44). PazePC is known to be present in LDL (3). It is tempting to speculate that ester formation between the AZ chain of PazePC and cholesterol might be one possible modulation route of OXPL-mediated heart disease, and of cholesterol trafficking in general. However, such PazePC-cholesterol esters have not been detected in LDL, and neither have enzymes that can catalyze the reaction been isolated or characterized.

Langmuir balance and fluorescence spectroscopy experiments have shown that the intercalation of positively charged antimicrobial peptides into lipid monolayers and liposomes was increased by addition of anionic lipids or PoxnoPC, but was not enhanced by addition of PazePC (16). In contrast, the simulations presented here suggest that presence of PazePC should also enhance association of cationic antimicrobial peptides by presenting negatively charged groups on the membrane interface. The disagreement can be partly reconciled by inspecting the electrostatic potential profiles for PazePC and PoxnoPC in Fig. 10. A positively charged particle will experience a lower dipolar potential barrier near a PoxnoPC membrane than near a PazePC membrane. The observation is counterintuitive considering the charged nature of PazePC. The deep binding of sodium ions (see next paragraph) is partly responsible for the attenuation of the electrostatic force that a peptide might experience as is approaches the PazePC interface.

The comparison of the impact of PoxnoPC and PazePC on lipid bilayers must be interpreted with one caveat: there were no sodium counterions present in the PoxnoPC simulations. The reversal of AZ chains into the aqueous phase was very fast, on the time scale of 10 s of picoseconds. The area per lipid relaxed to equilibrium values quickly (~5 ns) in PoxnoPCcontaining bilayers. However, in the PazePC simulations, the area per lipid relaxed slowly, in ~40–50 ns, because of the slow binding of cations to the interface, similar to that observed in past simulations (18,45–49). In all these cases, cations bound preferentially to the ester region of the phospholipids and led to overall compression of the lipid bilayer accompanied by an 67

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increase in order parameters of the acyl chain carbon atoms close to the headgroups (18,45â&#x20AC;&#x201C;53). Thus, in simulations with the Berger force field (24) for lipids, cations have an overall condensing effect on the lipid bilayer.

Developing force fields for ions have proven to be an unexpectedly difficult proposition (54â&#x20AC;&#x201C;57), and it is not entirely resolved whether or not the condensing effect of salt is exaggerated in the Berger force field, because similar detailed studies on long time scales have not been performed with other force fields. The structural properties derived from the PazePC simulations are thus controlled by two competing forces: the condensing effect of sodium cations and the expansion of the bilayer induced by reorientation of the carboxyl chains.

When the sodium ions in the 25% PazePC simulation were replaced by a uniform charge neutralizing plasma, the membrane thinned along the bilayer normal, and the area per lipid increased significantly. Without sodium counterions, the expansion of the lipid bilayer was higher in the PazePCcontaining bilayer than in the PoxnoPC-containing bilayer. This is in agreement with Langmuir monolayer observations, where PazePC expanded the monolayer more than PoxnoPC (12). Moreover, the order parameters dropped significantly in 25% PazePC when the sodium ions were replaced by the uniform charge density. The results thus establish that the condensation effect seen in lipid bilayers is a result of the strong binding of sodium to the lipid headgroups. The agreement of the sodium-free simulations with the monolayer experiments suggest that the intercalation of sodium ions in the lipid headgroups, and the consequent condensing effect might be a force-field artifact.

In this work, the carboxylic acid group of the AZ chain of PazePC was kept deprotonated. Is it possible that the carboxylic group can pick up a proton in the lipid environment? Free energy profiles of amino acids across lipid bilayers showed that the carboxylic acid group remains protonated in the hydrophobic core of the bilayer (58). However, the protonated carboxylic acid group is more polar than the carbonyl group, and therefore even the protonated AZ chain is expected to reorient to the interfacial region of the lipid bilayer. The apparent pKa of carboxylic acid group of phosphatidylserine lipids is 5.5 (59), so it is reasonable to assume that the carboxylic acid group of PazePC will be mostly deprotonated near the lipidwater interface.

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When the orientation of the AZ chain reverses, the headgroup of PazePC can be envisioned to become extraordinarily large, because it now comprises the conventional lipid headgroup plus the reversed AZ chain residing in the aqueous phase. The shape of PazePC then resembles the wedge shape of lysolipids, which only have a single hydrophobic acyl chain pendant on the headgroup. Lysolipids are nonlamellar-forming lipids and, owing to their conical shape, have tendency to promote hexagonal HI structures (60).

Lysolipids can thus alter the curvature stress profile in mixed bilayers (61,62). The presence of PazePC in membranes could alter the curvature stress field of the bilayer, which could eventually lead to domain separation, depending on the local lipid composition and other environmental factors such as temperature and ionic strength. Given the larger size of the PazePC headgroup, the effect might be greater than for lysolipids. Domain separation in DLPC bilayers could be induced at much lower concentrations of cholesterol when the lipids were subject to peroxidation (63).

Interestingly, the small headgroup of cholesterol gives it an inverted conical shape and promotes the formation of inverted hexagonal H II structures (60).

We are pursuing efforts to investigate the phase behavior of cholesterolPazePC-DLPC mixtures using coarse-grained MD methods (35,64,65).

Coarse-grained MD methods will also allow for measurement of the mechanical properties of bilayers, specifically the area compressibility modulus and the bending rigidity. The bending rigidity of giant unilamellar vesicles of POPC was decreased in the presence of lysolipids in micropipette aspiration experiments (John H. Ipsen, personal communication, 2008), and it is possible that PazePC and PoxnoPC also have significant impact on the mechanical strength of membranes.

Go to: Conclusion This work provides the first molecular-scale evidence that oxidized lipid acyl chains can undergo complete chain reversal and adopt the long-debated â&#x20AC;&#x153;extended lipid conformationâ&#x20AC;? without the requirement of interaction with external hosts. Although chain reversal has a disordering effect on the bilayer, the overall integrity of the bilayer was preserved up to 25% mole fraction OXPL. OXPLs are known to participate in the genesis of a variety of serious ailments including cancer, apoptosis, and heart disease. The reorientation of 69

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polar acyl chains presents reactive functional groups near the membrane, which are capable of noncovalent and covalent, specific and nonspecific interactions with a large variety of membrane hosts, ranging from single ions to large proteins. Our work provides a clear structural model that will help comprehend and visualize such interactions better, which will lead to a better understanding of how OXPLs participate in the genesis of diseased states that are especially prevalent in tissues with oxidative environments, such as inflammation sites in cancer and in microbial infections.

Go to: Acknowledgments The Danish Center for Scientific Computing at the University of Southern Denmark, Odense is acknowledged for computing resources. H.K. is supported by MEMBAQ, a Specific Targeted Research Project supported by the European Commission under the Sixth Framework Programme (Contract NMP4-CT-2006-033234). MEMPHYS - Center for Biomembrane Physics is supported by the Danish National Research Foundation.

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Stress fractures of the distal radius in adolescent gymnasts M. T. F. Read Copyright and License information â&#x2013;ş This article has been cited by other articles in PMC. Abstract Adolescent girl gymnasts sustained stress fractures of the distal end of the radius in the wrist on which a rotational vault was performed. The history and clinical progress were typical of stress fractures.

Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

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Selected References These references are in PubMed. This may not be the complete list of references from this article.  

Farquharson-Roberts MA, Fulford PC. Stress fracture of the radius. J Bone Joint Surg Br. 1980 May;62-B(2):194–195.[PubMed] Frykman G. Fracture of the distal radius including sequelae--shoulderhand-finger syndrome, disturbance in the distal radio-ulnar joint and impairment of nerve function. A clinical and experimental study. Acta Orthop Scand. 1967;(Suppl):3+–3+.[PubMed]

Injuries of the spine sustained during gymnastic activities.

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J R Silver, D D Silver, and J J Godfrey Copyright and License information â&#x2013;ş This article has been cited by other articles in PMC. Abstract Between 1954 and 1984, 38 patients were seen as a result of gymnastic activities. Thirty three were men, five were women, and their ages ranged from 12 to 54, the mean age being 20. Thirty one had spinal injuries (28 in the cervical region, three in the thoracolumbar region), two no definite injury, and for five the information was incomplete. The accidents occurred largely because gymnasts landed on their heads, the force being transmitted to the cervical spine. Most took place in gymnasiums and were caused by a failure of supervision.

Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (851K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

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The Left Hand Second to Fourth Digit Ratio (2D:4D) Does Not Discriminate World-Class Female Gymnasts from Age Matched Sedentary Girls Maarten W. Peeters* and Albrecht L. Claessens Author information ► Article notes ► Copyright and License information ► Go to: Abstract Introduction The second to fourth-digit-ratio (2D:4D), a putative marker of prenatal androgen action and a sexually dimorphic trait, has been suggested to be 94

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related with sports performance, although results are not univocal. If this relation exists, it is most likely to be detected by comparing extreme groups on the continuum of sports performance.

Methods In this study the 2D:4D ratio of world-class elite female artistic gymnasts (n = 129), competing at the 1987 Rotterdam World-Championships was compared to the 2D:4D ratio of sedentary age-matched sedentary girls (n = 129), alongside with other anthropometric characteristics including other sexually dimorphic traits such as an androgyny index (Bayer & Bayley) and Heath-Carter somatotype components (endomorphy, mesomorphy, ectomorphy) using AN(C)OVA. 2D:4D was measured on X-rays of the left hand.

Results Left hand 2D:4D digit ratio in world class elite female gymnasts (0.921±0.020) did not differ significantly from 2D:4D in age-matched sedentary girls (0.924±0.018), either with or without inclusion of potentially confounding covariates such as skeletal age, height, weight, somatotype components or androgyny index. Height (161.9±6.4 cm vs 155.4±6.6 cm p<0.01), weight (53.9±7.6 kg vs 46.2 6.3 kg p<0.01), BMI (20.51±2.41 kg/m2 vs 19.05±1.56 kg/m2), skeletal age (15.2±1.1 y vs 14.5±1.2 y p>0.01), somatotype components (4.0/3.0/2.9 vs 1.7/3.7/3.2 for endomorphy (p<0.01), mesomorphy (p<0.01) and ectomorphy (p<0.05) respectively) all differed significantly between sedentary girls and elite gymnasts. As expressed by the androgyny index, gymnasts have, on average, broader shoulders relative to their hips, compared to the reference sample.

Correlations between the 2D:4D ratio and chronological age, skeletal age, and the anthropometric characteristics are low and not significant.

Conclusion Although other anthropometric characteristics of sexual dimorphism were significantly different between the two samples, the present study cannot discriminate sedentary girls from world-class female gymnasts by means of the left hand 2D:4D ratio.

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Introduction Although the ratio of the length of the second (index) finger to the length of the fourth (ring) finger (2D:4D) has been the subject of much recent research [1]–[11] the sexually dimorphic nature of this ratio has been reported for over more than 60 years [12]. The ratio represents an individual difference variable putatively related to prenatal gonadal hormonal exposure. A lower 2D:4D is indicative of relatively higher prenatal testosterone than estrogen levels, which means that men may have, on average, lower digit ratios than women [13]. Several studies indicate that the digit ratio is related with psychological characteristics like assertiveness and aggression [13], with the onset of menarche [4], [14], with homosexuality [13], with success among financial traders [15], and with neck circumference, indicating that in men a higher 2D:4D ratio is associated with greater risk of obesity and heart disease [16].

A number of studies gave investigated the associations between 2D:4D and sporting ability or physical fitness [1]–[3], [5], [7], [9], [11], [17]–[24]. The hypotheses set up in these studies were that a lower digit ratio is related to better sport abilities or better motor performance, in both males and females.

Overall, results of the studies are not consistent and in part difficult to compare because of the use of different procedures for measuring the digit lengths. In some studies where both sexes are included the relation is found in both men and women [3], [18], [22], although in the study of Hönekopp et al. [18] the relation in women was significant only for the left hand 2D:4D and not for the right hand 2D:4D and vice versa in men. Other studies found a significant relation in men but not in women [7] and vice-versa [11]. Fink et al [17] reported a relation between 2D:4D and hand-grip strength in men, but this was not replicated in men [24] nor found in women [23], [24]. A number of studies found the relationship between sporting ability and digit ratio in both right and left 2D:4D [1], [7] in right hand 2D:4D but not in left hand 2D:4D [2], [11], [17] or vice versa [21] with the mean of right and left 2D:4D [9] or neither with right nor left 2D:4D [5], [24], but only with the difference between right and left 2D:4D [5]. In a meta-analysis Hönekopp and Schuster [25] reported that for the association between 2D:4D digit ratio and athletic prowess neither hand outpredicted the other. Also, in many studies sporting abilities were not measured objectively, but based on information reported by the subjects themselves [9], [22]. In addition, many of the published studies on sporting ability and 2D:4D focused on physical fitness or sport ability in general or a combination of sports and not on one 96

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specific sport, and studies including both sedentary subjects and objectively assessed elite-status athletes are limited [1].

To our knowledge, a study that focuses on a large sample of elite female gymnasts to investigate the association between the digit ratio and artistic gymnastic performance is not available. If indeed there is an association between digit ratio and sporting ability it is most likely to be detected by comparing extreme groups on the continuum of sports performance. The main aim of this study therefore was to compare the 2D:4D ratio of worldclass elite female artistic gymnasts with the 2D:4D ratio of sedentary agematched reference girls. It is hypothesized that the group of elite gymnasts have a significant lower digit ratio compared to the reference group.

Go to: Materials and Methods Samples Gymnast sample The sample (n = 129) of elite female gymnasts was a sub-sample of the participants of the 24th World Championships Artistic Gymnastics held at Rotterdam, The Netherlands, in 1987, which has been previously described [26]–[28]. Because the reference sample (see below) consisted of Caucasian girls up to 18.5 yrs old, and 2D:4D varies with ethnicity [13] we selected only gymnasts of Caucasian ethnicity and ages up to 18.5 yrs. Their chronological age varied from 13.2 to 18.5 years, with a mean age of 16.1±1.2 years. The study in the frame of which this dataset was collected was approved by the Medical Ethics Committee of the Institute of Physical Education of the Catholic University of Leuven and by the Medical committee of the Fédération Internationale de Gymnastique (FIG). Prior to the championships, the national gymnastics federation of each participating country was contacted about the study by the Medical committee of the FIG. Subsequently the delegation chiefs, coaches, and/or medical officers as legal guardians for the minors during the competition, were personally approached at the competition site for permission to contact individual athletes and to perform the measurements in their presence. Only if the delegation chief, coach and/or medical officer provided permission, the individual gymnasts were contacted, informed about the study and provided 97

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verbal consent if they wanted to cooperate. The procedure for contacting the delegation chiefs, coaches and medical officers and the individual athletes and obtaining verbal consent was approved by the Medical Ethics Committee of the Institute of Physical Education of the Catholic University of Leuven and by the Medical committee of the FIG [28]. All data was analyzed anonymously.

Reference sample Girls from the Leuven Growth Study of Flemish Girls (LGSFG) [29] were used as the reference sample. The LGSFG (n = 9414 girls between 6–18 years) was a representative sample of the Flemish population in the academic year of 1979–1980. The sampling was done with the guidance of the Statistical Service of the Belgian Ministry of education using a multistage procedure. In the first stage a proportionate stratified sample with schools as the primary sampling cluster was selected. This sample included 43 primary schools and 45 secondary schools. In the second stage, all students in a single classroom at each grade level were selected within each school [29]. From this study a sample of 129 age-matched girls was selected.

The matching by chronological age was accurate within 0.1 year. Besides this, only reference girls with the following conditions were selected: (1) girls for whom an X-ray of the left hand was available; and (2) girls must be sedentary, i.e. not practice any sports apart from the mandatory 2 hours/week of physical education classes in school, to be sure of a significant difference in sporting ability between the two samples. The mean chronological age of the selected girls was 16.1±1.3 years, varying from 13.2 to 18.4 years. The Leuven growth study of Flemish Girls was approved by the Medical Ethics Committee of the Institute of Physical Education of the Catholic University of Leuven. Written informed consent was given by the school authorities at the national and local levels, and by the parents of the children [29].

Anthropometric dimensions The following measurements were taken: weight; height; biacromial and bicristal breadths; humerus and femur widths; biceps and calf girths; and triceps, subscapular, supraspinale, and calf skinfolds. All bilateral measurements were taken on the left side of the body. Body mass index (BMI) was calculated as weight (kg) / height (m2). All measurements were

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taken by well-trained observers according to the measuring procedures as described by Claessens et al. [30].

Body ratio of sexual dimorphism The androgyny index: the Bayer-Bayley ratio (Androgyny Index, IANDR) [31] relates the breadth of the hips (lower trunk, bicristal breadths) to that of the shoulders (upper trunk, biacromial breadth).

On average the ratio is higher in girls than in boys at virtually all ages during childhood and adolescence, and this difference persists into adulthood.

This index is a useful indicator of sex differences in the proportional relationship of the shoulders and hips [31]â&#x20AC;&#x201C;[33].

Somatotype The three somatotype components endomorphy, mesomorphy and ectomorphy were anthropometrically determined according to the HeathCarter technique. The Heath-Carter anthropometric somatotype is calculated from 10 dimensions: weight; height; triceps, subscapular, supraspinale, and calf skinfolds; humerus and femur widths; and biceps and calf girths.

Endomorphy is derived from the sum of three skinfolds (triceps, subscapular, supraspinale) adjusted for height. This component describes the relative degree of fatness of the body. Mesomorphy is derived from humerus and femur widths, biceps and calf circumferences corrected for the triceps and calf skinfolds respectively, and height. The four limb measurements are adjusted for height. This component expresses the relative degree of muscle, bone and connective tissue. Ectomorphy is based on the somatotype ponderal index: height (cm) divided by weight (kg)1/3. This component characterizes the degree of linearity, slenderness, and fragility of body build, with poor muscular development, and a predominance of surface area over body mass. For a detailed description how the three components were calculated reference is given to Claessens et al. [32].

Skeletal age An X-ray of the left hand and wrist of each subject was taken for the assessment of skeletal maturity. An Elinax 60 (62 kV, 15mA) assembled in a 99

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portable apparatus was used. Skeletal age (Skel.age) was estimated using the radius-ulna-short bone protocol in the Tanner-Whitehouse II method. With this method, the maturity status of the radius, ulna, the first, third, and fifth metacarpals, and phalanges of the first, third and fifth fingers are rated, the bone-specific scores are summed into a maturity score, and the maturity score is converted to a skeletal age. For more detailed information reference is given to Claessens et al. [32].

Measuring 2D and 4D lengths Measuring procedure Radiographs from the left hand of all the subjects of the two samples were available to measure and calculate 2D:4D. The lengths of the second and fourth finger were measured from the proximal end of the proximal phalanx to the distal tip of the distal phalanx using a caliper accurate to 0.1 mm (John Bull British Indicators LtD, England). Digit lengths of each sample were measured by two raters. The mean of the two raters was taken as the final measurement.

Reliability study Before measuring all X-rays, a reliability study was conducted by three different raters. This study consisted of the measurement of thirty left-hand X-rays twice by each rater in a test and re-test manner. Interobserver measurement repeatabilities for 2D:4D ratios were assessed with intraclass correlation coefficients (ICC). The ICC for interrater reliability showed a reliability of 0.98. Anova did not show any significant difference for 2D:4D between the raters. The technical error of measurement for all raters was <0.001 for 2D:4D. It therefore can be concluded that all measurements of 2D:4D were measured reliable.

Statistical analyses Differences in 2D:4D and in anthropometric characteristics between the sample of elite gymnasts and the reference group were analyzed by means of a two-tailed t-test. If a standard deviation for the digit ratio of 0.02 is assumed and a 0.01 difference in digit ratio between the two samples is to be detected, the statistical power of the present study is 0.98 when alpha = 0.05.

An ANCOVA (Proc GLM, SAS 9.1.3) was used to compare the two samples for each variable with skeletal age as the covariate. The relationship 111

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between 2D:4D ratio and anthropometric characteristics for each sample were calculated by Pearson Product Moment correlation coefficients. The Statistical Analysis System program 9.1.3 (SAS Institute, Cary, NC, USA) was used to analyze the data.

Go to: Results Descriptive statistics (mean ± SD) of all variables for both samples are given in Table 1.

Table 1 Descriptive statistics.

Mean chronological ages of both samples do not differ significantly, as expected, whereas skeletal age of the gymnasts' sample is significantly lower compared to the skeletal age of the reference girls, 14.5±1.2 and 15.2±1.1 respectively. Height, weight and BMI of the elite gymnasts are significantly lower compared to the reference sample. Also, marked differences in somatotype between the two groups of girls can be observed. Gymnasts are more mesomorph and ectomorph, and less endomorph compared to reference girls, with mean somatotypes of 1.7/3.7/3.2 and 4.0/3.0/2.9 respectively. As expressed by IANDR, gymnasts have, on average, broader shoulders relative to their hips, compared to the reference sample. No significant difference between both groups for the digit ratio can be observed, 0.924±0.018 and 0.921±0.020 for the reference girls and gymnasts respectively. Because of the significant difference in skeletal age between the two samples, skeletal age was added as a covariate in an ANCOVA. The adjusted means of the 2D:4D ratio and of the anthropometric characteristics are given in Table 2.

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Table 2 Adjusted means of 2D:4D and of the anthropometric characteristics (ANCOVA with skeletal age as co-variate).

Although all variables were adjusted for skeletal age, it is observed that all the adjusted mean differences for the anthropometric variables between the two samples are still significant, with the exception of the ectomorphy component. Adjusted mean values for the 2D:4D ratio for both samples did not change as compared to the absolute means. Results similar to those reported in table 2 were obtained for the 2D:4D when covarying for the anthropometric measurements and indices (results not shown).

Correlations between the 2D:4D ratio on the one hand and chronological and skeletal ages, and the anthropometric characteristics on the other hand are low and not significant (p>0.05), ranging from r = 0.11 (with skeletal age) to r = −0.16 (with height) in the reference sample, and from r = 0.15 (with height) to r = −0.10 (with mesomorphy) in the gymnasts sample.

Go to: Discussion The present study shows that left hand 2D:4D digit ratio in world-class elite gymnasts is not different from left hand 2D:4D digit ratio in age matched sedentary girls. However both groups are significantly different for a number of objectively measured anthropometric characteristics which shows that the gymnast do have a more „masculine' body morphology. For the gymnasts' sample, we hypothesized a lower 2D:4D ratio, compared to the value found for the reference sample, but no significant difference between both mean ratios was observed ( 0.924±0.018 and 0.921±0.020 for the reference girls and gymnasts respectively). So the 2D:4D ratio, on average, may not be a discriminating factor for artistic gymnastic performance. This is consistent 112

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with the findings of a study by Paul et al. [9] about the relationship between 2D:4D and sporting ability across a range of 12 sports in a sample of 607 female participants. The subjects were asked to give the highest competitive level in their sport activity on a five-point scale, with „social participation only‟ as the lowest level ( = 1) and „national level‟ ( = 5) as the highest level.

Measurements of the digit lengths were done on X-rays. The overall ageadjusted level achieved in any sport was significantly negatively associated with mean 2D:4D. But, when analyzed separately, mean digit ratio was only significantly associated with running level. There was no significant relationship between 2D:4D and the level in a subsample of female gymnasts. A mean left-hand 2D:4D ratio of 0.93±0.02 was found, which is similar to the value of 0.92 found in the present study.

The findings of our study are consistent with the findings of Paul et al. [9] for gymnasts and with those on other measures of sporting abilities in women such as ergometer rowing performance [7], national or international fencing ranking with left 2D:4D [2], [11], and handgrip strength [23], [24].

However they are in contrast with studies in which significant relationships between 2D:4D and sporting ability in females were observed with the dominant hand 2D:4D [3], the left hand 2D:4D [21], or the right hand 2D:4D [2], [11], [22] although none of these studies contrasted world-class elite athletes with sedentary reference samples.

The 2D:4D ratio is moderately related to performance in endurance running of young adults with correlations varying from r = 0.30 to r = 0.50 [19]. In contrast little evidence is found for the relationship between 2D:4D and acceleration and strength. Correlation coefficients between 2D:4D and sprinting speed in boys were weak (r = 0.15; p = 0.02) in a study by Manning & Hill [20]. van Anders (2007) found no significant association between 2D:4D and grip-strength in a sample of 99 women (mean age 23.76±5.66 years) and neither did Gallup et al. [24]. This suggests that the widespread relationship between 2D:4D and sport performance may have more to do with aerobic efficiency than with strength and acceleration [20] although speed is also crucial in fencing [2], [11]. It is possible that strength and acceleration are two more important modifying determinants in artistic gymnastic performance, compared to aerobic capacity and hence our results are consistent with the lack of evidence for an association between handgrip strength and 2D:4D in women [23], [24]. The physical capacities that serve as a basis for gymnastic talent are speed, quickness, flexibility and strength [34]. Gymnasts do not perform competitive routines longer than 90 seconds.

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Therefore, the oxidative energy system is probably not a dominant energy system for gymnastics. The anaerobic dominance of gymnastic performance is supported by several studies [35].

The androgyny index and somatotype are, just like the 2D:4D ratio, determinants of sexual dimorphism. Men have on average a lower 2D:4D ratio [13], a higher mesomorphy component, a lower endomorphy component, and a lower value for the androgyny index, compared to women [31]–[33]. As expressed in several previous studies [27] elite female gymnasts demonstrate a more „masculine‟ body morphology compared to age-related reference girls. This is also demonstrated in the present study.

The sample of elite gymnasts has significant lower IANDR, which means that the gymnasts have on average broader shoulders relative to their hips, compared to the reference girls, 73.11 and 76.39 respectively for the BayerBayley index. When looking at the body as a „Gestalt‟, a significant difference was found in somatotype between the two samples. Gymnasts demonstrated on average a somatotype of 1.7/3.7/3.2 compared to an average somatotype of 4.0/3.0/2.9 of the reference sample. Elite gymnasts are characterized by an ecto-mesomorphic somatotype whereas reference girls are characterized as meso-endomorphic. Mesomorphy is characterized by the predominance of muscle, bone and connective tissue, whereas endomorphy describes the degree of roundness and fatness of the body.

Although both samples can be sexually discriminated on the basis of anthropometric characteristics, the left hand 2D:4D ratio does not.

In addition, when testosterone is negatively related to 2D:4D [13], it is expected that more „male‟ forms of 2D:4D would correlate with more „male‟ forms of anthropometric characteristics like androgyny indices and somatotype. Some previous studies have investigated the relationship between 2D:4D and anthropometric characteristics. Fink et al. [36] investigated the relationship between 2D:4D with body mass index, waistto-hip ratio and waist-to-chest ratio. Some evidence was found that 2D:4D also correlates with indices of sexually dimorphic traits of the human body.

Body fat distribution was in that study measured by the waist-to-hip ratio.

However, no significant associations were observed for male and female 2D:4D and the waist-to-hip ratio. In females, no significant relationship between body mass index and 2D:4D was found. A higher value of 2D:4D correlated significantly with a lower value of the waist-to-chest ratio. This is consistent with the literature as oestrogens should largely influence chest circumference in females. In a study by Gallup et al. [24] the relationship 114

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between handgrip strength and three measures of body morphology (shoulder-to-hip ratio, waist-to-hip ratio, 2D:4D) was investigated in a sample of 82 male and 61 female college students. A significant positive relationship between 2D:4D and waist-to-hip ratio in females could be observed. This however is contrary to what might be hypothesized if both traits indeed are sexually dimorphic: a lower waist-to-hip ratio reflects a female fat â&#x20AC;&#x201C; distribution pattern while a lower 2D:4D reflects the more masculine phenotype of the digit ratio. Hence the results of Gallup et al. [24] suggest that a lower, andtherefore more masculine, digit ratio is related to amore feminine fat patterning as reflected by the lower waist-to-hip ratio.

Because mostly different body ratios of sexual dimorphism were used in the literature compared to the one used in the present study, comparison of results remains difficult. Since the IANDR used in the present study is based in essence on bone-measurements, it might have been expected that a relation between this sexually dimorphic trait and the digit ratio was more likely than that with circumference measurements related to fat patterning.

Although most of the anthropometric characteristics used in the present study were discriminating factors between the gymnasts and the reference samples, no significant correlations were observed between 2D:4D and any of these anthropometric characteristics. Therefore adding them as covariates in an Ancova did not alter the results (table 2), not even for height (results not shown), the only trait that might be considered to be more masculine in the reference sample and therefore might have potentially â&#x20AC;&#x17E;maskedâ&#x20AC;&#x; a difference in 2D:4D digit ratio between both groups.

The present study is to our knowledge the first study that investigated the relationship between 2D:4D in a large sample of female gymnasts of worldclass level (n = 129), by comparing their 2D:4D ratio with that of an agematched reference sample (n = 129) of sedentary girls. The high level of the gymnasts' sample is based on the fact that all gymnasts participated at the World Championships Artistic Gymnastics held in Rotterdam, 1987 [26], [27]. The reference sample consisted of girls who were all sedentary. There was thus an obvious difference in sporting ability between both groups. In many studies about the relationship between sporting ability and 2D:4D, the level of sporting ability was based on information reported by the subjects themselves. Furthermore, in the present study, all anthropometric variables were measured objectively; whereas in a lot of previous studies data (e.g. height and weight) were reported.

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It may be noted that the mean value of 0.924 (SD = 0.018) for the 2D:4D ratio found for the reference sample is quite low compared to e.g. 2D:4D ratio from a sample of 531 females which had a mean 2D:4D ratio of 1.00 (SD = 0.03) [13]. This low value is however not entirely unexpected since, although this was not verified in the present study, Manning et al. [37] had already observed that mean radiograph-derived 2D:4D showed lower ratios than those from photocopies and showed less sexual dimorphism although they are significantly correlated. Therefore a possible explanation for this low mean value observed for our reference sample is that the digit lengths were measured on X-rays in contrast to the measuring procedures used in many other studies in which mostly digit lengths were measured on photocopies, printed scans or directly from the hand. Previous studies have compared different methods of digit ratio measurement [13], [38]â&#x20AC;&#x201C;[40]. The fact that measurements on X-rays seem to yield lower digit ratios may be partially explained by the fact that measurements made on soft tissue or images of the soft tissue on the hand are taken approximately halfway along the proximal phalanx whereas bone measurements begin at the proximal end of the phalanx [13]. This hypothesis has not been subject to research yet but could possibly provide an explanation and may lead to standardization for the measurement of the 2D:4D ratio. At the same time when measuring on photocopies, printed scans or directly on the hand, the soft tissue is also measured whereas when measuring finger lengths on X-rays only the bone length is recorded. In a study of Paul et al. [41], concerning the heritability of the 2D:4D ratio, measurements of the finger lengths were also made on X-rays. In a sample of 456 female twin pairs a mean 2D:4D ratio of 0.92 (SD = 0.001) was observed for both hands, which is similar to the 2D:4D ratio found in the present study. Although it was not formally tested in the present study, the analogy with findings from the literature regarding different methods of determining finger lengths, it seems plausible that the low 2D:4D ratio of 0.924 found in our reference sample is the result of the fact that the measurements were done on X-rays.

A possible limitation of our study is that all measurements of the digit lengths were taken on the left hand. In most studies the digit lengths were taken on the right hand to calculate 2D:4D. This is based on the fact that results of previous studies have suggested that sex differences in 2D:4D and correlations of 2D:4D with target traits are more pronounced for the right hand than for the left hand [6] Testosterone-dependent physical traits tend to be more strongly expressed on the right side of the body compared to the left side [13], however a meta-analyses focusing specifically on the relation 116

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between the 2D:4D digit ratio and athletic prowess demonstrated that neither hand outpredicts the other. [25].

In conclusion, although other anthropometric characteristics of sexual dimorphism were significantly different between the two samples, the present study cannot discriminate sedentary girls from world-class gymnasts by the left hand 2D:4D ratio. Furthermore, no significant correlations were found between left hand 2D:4D ratios and anthropometric and age characteristics, both chronological and skeletal.

Go to: Acknowledgments The authors wish to thank the students Lara Lefevre, Nicky Taelen and Sven De Cleyn for measuring all X-rays.

Go to: Footnotes Competing Interests: The authors have declared that no competing interests exist.

Funding: MWP is supported by the Research Foundation Flanders as a post doctoral fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript Go to: References 1. Bennett M, Manning JT, Cook CJ, Kilduff LP. Digit ratio (2D:4D) and performance in elite rugby players. J Sports Sci. 2010;28:1415â&#x20AC;&#x201C; 1421.[PubMed] 2. Bescos R, Esteve M, Porta J, Mateu M, Irurtia A, et al. Prenatal programming of sporting success: associations of digit ratio (2D:4D), a putative marker for prenatal androgen action, with world rankings in female fencers. J Sports Sci 27. 2009;625â&#x20AC;&#x201C;632:909775472.

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35. Sands WA, Caine DJ, Borms J. Scientific aspects of women's gymnastics. Basel: Karger. 2003.

36. Fink B, Neave N, Manning JT. Second to fourth digit ratio, body mass index, waist-to-hip ratio, and waist-to-chest ratio: their relationships in heterosexual men and women. Ann Hum Biol. 2003;30:728–738.[PubMed] 37. Manning JT, Trivers RL, Thornhill R, Singh D. The 2nd:4th digit ratio and asymmetry of hand performance in Jamaican children. Laterality.

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2006;9:215–219.[PubMed Strength and flexibility in gymnasts before and after menarche.

K. M. Haywood Copyright and License information ► 111

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Abstract simple anthropometric measures, flexibility, and strength performance tests were conducted on 30 young gymnasts and repeated one year later. During the intervening year, 13 gymnasts, average age 14.5 at the second year, reached menarche, while the remaining 17, average age 14.1 years, did not.

Multivariate analyses of covariance were calculated to test for differences between the groups at Year 2, using the Year 1 scores as covariates. No significant differences between the groups were found. Tendencies to linearity of physique and late maturation, noted in the literature among very skilled gymnasts, seemed to be confirmed among this group of local competitors.

Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (704K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

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Selected References These references are in PubMed. This may not be the complete list of references from this article. 

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Malina RM, Bouchard C, Shoup RF, Demirjian A, Lariviere G. Age at menarche, family size, and birth order in athletes at the Montreal Olympic Games, 1976. Med Sci Sports. 1979 Winter;11(4):354– 358.[PubMed] Munroe RA, Romance TJ. Use of the Leighton flexometer in the development of a short flexibility test battery. Am Correct Ther J. 1975 Jan-Feb;29(1):22–25.[PubMed]

The cell-specific activity of the estrogen receptor αmay be fine-tuned by phosphorylation-induced structural gymnastics Valentina Gburcik and Didier Picard Author information ► Article notes ► Copyright and License information ► This article has been cited by other articles in PMC. Go to: Abstract The estrogen receptor α (ERα) regulates the transcription of target genes by recruiting coregulator proteins through several domains including the two activation functions AF1 and AF2. The contribution of the N-terminally located AF1 activity is particularly important in differentiated cells, and for ERα to integrate inputs from other signaling pathways. However, how the phosphorylation of key residues influences AF1 activity has long remained mysterious, in part because the naturally disordered AF1 domain has resisted a structural characterization. The recent discovery of two coregulators that are specific for a phosphorylated form of AF1 suggests that phosphorylation, possibly in conjunction with the subsequent binding of these coregulators, may enforce a stable structure. The binding of the "pioneer" coregulators might facilitate the subsequent recruitment of yet other coregulators.

Different AF1 folds may be enabled by the combinatorial action of posttranslational modifications and coregulator binding thereby fine-tuning ERα activities in a cell- and promoter-specific fashion.

Go to: Introduction ERα is a member of the nuclear receptor superfamily, and mediates the responses to estrogens as well as a variety of other extracellular signals by 121

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signaling crosstalk. As a nuclear receptor, it harbors a receptor function, DNA-binding capacity and transcriptional activation functions all within the same molecule. Transcriptional regulation by ERα is mediated by the two activation functions AF1 and AF2. These activation functions represent docking surfaces on the receptor through which corepressors and coactivators are recruited. The particular combination of recruited coregulators determines the assembly of the general transcription machinery on the promoter and the resulting gene expression pattern.

AF2 lies within the ligand binding domain (LBD) of ERα and is induced upon binding of an agonist [Nagy and Schwabe, 2004; Steinmetz et al., 2001]. Depending on the exact chemical nature of the ligand and the precise allosteric rearrangements it induces in the LBD, coactivators or corepressors are recruited [Nettles and Greene, 2005]. The AF1 domain is located in the N-terminal region of ERα. The intrinsically constitutive activity of AF1 is unleashed by agonist binding to the LBD, but various signaling pathways also stimulate its activity, in part by direct phosphorylation of several serines [Ali et al., 1993; Bunone et al., 1996; Chen et al., 2000; Kato et al., 1995] (see also below). To the extent that AF1 can be dissected at all, different regions of AF1 have been shown to have distinct cell-type and promoter selectivity [McInerney and Katzenellenbogen, 1996; Metivier et al., 2000; Metzger et al., 1995; Tora et al., 1989].

Go to: Signaling crosstalk involves phosphorylation of AF1 During the last fifteen years, many investigators have reported that crosstalk between steroid- and growth factor-stimulated intracellular signaling pathways can affect the activity of nuclear receptors, and as a consequence the transcription of target genes [Cenni and Picard, 1999; Picard, 2003; Weigel and Zhang, 1998]. In the case of ERα, this involves the direct phosphorylation of the receptor, coactivators, and/or other regulatory proteins. A whole series of amino acid residues of ERα display basal and induced phosphorylation in response to ligands, growth factors and other regulatory molecules by MAPK, AKT, Rsk, protein kinases A and C, casein kinase II, CDK2, and CDK7 [Ali et al., 1993; Bunone et al., 1996; Campbell et al., 2001; Chen et al., 2000; Clark et al., 2001; Joel et al., 1998; Kato et al., 1995;Le Goff et al., 1994; Martin et al., 2000; Rogatsky et al., 1999; Tremblay et al., 1999] . Our understanding of the roles of all of these kinases 121

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and phosphorylation sites remains unclear. As far as AF1 is concerned, serine 118 (S118; numbering according to the sequence of the human ERα) is the main phosphorylation site that needs to be considered.

Go to: Specific recruitment of coregulators by the phosphorylated AF1 The key question is how the phosphorylation of ERα AF1 modulates its transcriptional activity. The mechanistic answer might depend on how this phosphorylation comes about, and on whether or not AF2 is also activated by cognate hormone, but it seemed reasonable from the beginning to speculate that the phosphorylation of S118 might stimulate the recruitment of a coactivator. However, serious candidates took a long time to be identified. Although the recruitment of p68 RNA helicase is stimulated by phosphorylation of S118, its stimulation of ERα activity is relatively weak, cell-specific and not strictly phospho-S118-dependent [Endoh et al., 1999; Watanabe et al., 2001]. A much more serious contender is the recently reported splicing factor SF3a120, a component of the U2 snRNP [Masuhiro et al., 2005]. Binding of SF3a120 to ERα, and stimulation of ERα activity by SF3a120 is fully dependent on the phosphorylation of S118. Moreover, SF3a120 promotes the effects of ERα on splicing of transcripts made from ERα target genes, and again this effect is dependent on the phosphorylation of S118. Thus, the recruitment of SF3a120 may account for much of the stimulatory effects of the phosphorylation of S118.

Surprisingly, the phosphorylation of S118 also allows the recruitment of a corepressor. We recently discovered the stromelysin-1 platelet-derived growth factor-responsive element-binding protein (SPBP) as the first protein whose binding to ERα is strictly dependent on phosphoserine 118 [Gburcik et al., 2005]. Unlike p68 and SF3a120, SPBP functionally behaves as a corepressor of activated ERα. We have speculated that the role of SPBP might be to attenuate the activity of AF1, and to allow only a transient activation.

Go to: Recruitment by phosphorylation-induced structural gymnastics In contrast to other nuclear receptor domains, there are no high-resolution structures available to date for the AF1 domain of any member of the 122

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nuclear receptor superfamily [Lavery and McEwan, 2005]. Its structure may be naturally disordered. AF1 domains appear to be structurally flexible with little stable secondary structure. This structural flexibility may provide the possibility for multiple different interactions [Dunker et al., 2002; Dyson and Wright, 2005]. Since different partner proteins may induce different conformations, they may in turn depend on cellular and promoter context.

Moreover, it is possible that the AF1 domain requires specific posttranslational modifications in order to be fully active [Kumar and Thompson, 2003]. Phosphorylation of AF1 may increase its helical content, which has been shown to correlate with increased activation potency in case of the peroxisome-proliferator activated receptors (PPARs) [Gelman et al., 2005].

Are SF3a120 or SPBP novel phosphoserine binding proteins? Competition and truncation experiments (data not shown) suggest that SPBP recognizes a specific AF1 fold induced by phosphorylation rather than the immediate context of the phosphorylated serine itself (see Figure 1). If we hypothesize that the phosphorylation of AF1 induces a conformational change or stabilization resulting in the generation of a docking site for a cofactor, several predictions are worth considering. Cofactors that interact with the phosphorylated AF1 might facilitate each other's recruitment (Figure 1A).

Anchoring one cofactor might further stabilize or structure the domain [Gelman et al., 2005; Lavery and McEwan, 2005], and allow the subsequent binding of a second factor (Figure 1B and C). In a different context, it had already been suggested that the recruitment of coactivators could facilitate the subsequent recruitment of other coactivators or even corepressors [Perissi and Rosenfeld, 2005]. Indeed, some of our preliminary results with combinations of SPBP and coactivators support this speculation (data not shown). We suggest that upon AF1 phosphorylation, coactivators such as SF3a120 are recruited first. They then facilitate the recruitment of SPBP, which acts as a corepressor, most likely by recruiting other corepressors such as NCoR [Gburcik et al., 2005]. The end result is that the strength and the duration of ERÎą activity are dampened. In this and other situations, alternative scenarios with an inverse order of binding or with cyclical exchanges are also conceivable.

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Figure 1 Coordinated binding of coregulators to AF1 depends on phosphorylation-induced structural changes.

This phosphorylation-induced gymnastics may itself be influenced by and complement additional "outside" inputs into AF1 structure. For example, binding of JDP-2 to the DNA binding domain of the progesterone receptor increases the helical contents of the N-terminus and AF-1 activity [Wardell et al., 2005], and sequence-specific allosteric effects of the DNA response element on receptor conformation have been recognized as a general principle for several nuclear receptors [Lefstin and Yamamoto, 1998] including ERα [Wood et al., 1998].

Go to: Physiological implications There may be many physiological consequences of this structural gymnastics induced by signaling crosstalk. To illustrate this point it should be sufficient to mention a few. In differentiated cells, AF1 may be the major transactivation function of ERα [Merot et al., 2004; Pendaries et al., 2002].

Therefore, SPBP might be an important determinant of the cell-specific activity pattern of ERα in differentiated cells. It might also play an important role in the organ-specific activity pattern of ERα during the estrous cycle, which has recently been monitored in a transgenic mouse model with a luciferase reporter gene under the control of activated ERs [Ciana et al., 2003]. Interestingly, the reporter activity in reproductive organs was synchronized with estrogen levels, while the peak of ER-dependent activity in non-reproductive organs did not correlate with estrogen levels. It was speculated that the latter activity might be due to ligand-independent activation of ERs by growth factors such as IGF-I. Whereas SPBP is not expressed in reproductive organs [Rekdal et al., 2000], the expression of SPBP might be cyclically induced in non-reproductive organs during the estrous cycle repressing ERα activity when estrogen peaks.

Signaling crosstalk of ERα with growth factors is also thought to contribute to resistance to endocrine therapy in breast cancer by stimulating AF1 phosphorylation and activity [Osborne et al., 2003; Osborne et al., 2005; Shou et al., 2004]. Hence, antiestrogen-resistant ERα-positive breast tumors 124

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would be expected to have lower SPBP levels. In contrast, ERα-negative breast tumors would not be adversely affected by the presence of SPBP. Rather they would benefit from the activating effects of SPBP on other growth-promoting transcription factors such as c-Jun [Rekdal et al., 2000].

Indeed, as we have previously pointed out [Gburcik et al., 2005], this inverse correlation between SPBP and ERα expression can be seen in a microarray analysis of breast tumor samples [van 't Veer et al., 2002].

Go to: Outlook The models discussed in this essay have several practical as well as biological implications. For example, the identification of certain AF1 coregulators may only be possible in the presence of a first-line coregulator.

Moreover, solving the structure of AF1 may require solving the structure of a complex between a phosphorylated AF1 and a coregulator. At a more mechanistic and physiological level, it will be interesting to fill in the details of how signaling crosstalk induces structural changes in AF1, and how this contributes to specifying and fine-tuning the physiological functions of ERα.

Go to: Acknowledgments This work was supported by the Swiss National Science Foundation, Krebsforschung Schweiz, the Fondation Médic, and the Canton de Genève.

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Epidemiology of injury in elite and subelite female gymnasts: a comparison of retrospective and prospective findings G. S. Kolt and R. J. Kirkby Copyright and License information ► This article has been cited by other articles in PMC. Abstract

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OBJECTIVES: An 18 month prospective injury survey was conducted on 64 Australian elite and subelite female gymnasts. The aims were to determine the rate of injury, anatomical location, and types of injury incurred by female competitive gymnasts, and to compare the findings with data collected retrospectively from the same sample of gymnasts. METHODS: The gymnasts recorded (weekly) in an injury record booklet the number of hours trained and information on any injuries suffered over that week.

RESULTS: The sample reported 349 injuries, a rate of 5.45 per person (6.29 for the elite and 4.95 for subelite gymnasts) over the 18 month survey.

Injuries to the ankle and foot (31.2%) were the most commonly reported, followed by the lower back (14.9%). The most prevalent type of injury were sprains (29.7%), followed by strains (23.2%), and growth plate injuries (12.3%). The elite gymnasts reported that, for each injury, they missed fewer training sessions (p = 0.01), but modified more sessions (p = 0.0001) than their subelite counterparts. Further, the elite gymnasts spent 21.0% of the year training at less than full capacity because of injury. Although a significantly higher number of injuries were recorded in the prospective study (p = 0.0004), no differences were found between the distribution of injury by anatomical location or type between the two methods of data collection. CONCLUSIONS: The findings have important implications in terms of training procedures and periodic screening of gymnasts.

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Caine D, Cochrane B, Caine C, Zemper E. An epidemiologic investigation of injuries affecting young competitive female gymnasts.

Am J Sports Med. 1989 Nov-Dec;17(6):811–820.[PubMed] Maffulli N, Bundoc RC, Chan KM, Cheng JC. Paediatric sports injuries in Hong Kong: a seven year survey. Br J Sports Med. 1996 Sep;30(3):218–221. [PMC free article][PubMed] Dixon M, Fricker P. Injuries to elite gymnasts over 10 yr. Med Sci Sports Exerc. 1993 Dec;25(12):1322–1329.[PubMed] Garrick JG, Requa RK. Epidemiology of women's gymnastics injuries. Am J Sports Med. 1980 Jul-Aug;8(4):261–264.[PubMed] Kolt GS, Kirkby RJ. Injury, anxiety, and mood in competitive gymnasts. Percept Mot Skills. 1994 Jun;78(3 Pt 1):955–962.[PubMed] Kolt Gregory, Kirkby Robert. Injury in Australian female competitive gymnasts: A psychological perspective. Aust J Physiother.

1996;42(2):121–126.[PubMed] Lindner KJ, Caine DJ. Injury patterns of female competitive club gymnasts. Can J Sport Sci. 1990 Dec;15(4):254–261.[PubMed] Lowry CB, Leveau BF. A retrospective study of gymnastics injuries to competitors and noncompetitors in private clubs. Am J Sports Med. 1982 Jul-Aug;10(4):237–239.[PubMed] Pettrone FA, Ricciardelli E. Gymnastic injuries: the Virginia experience 1982-1983. Am J Sports Med. 1987 Jan-Feb;15(1):59– 62.[PubMed] Sands WA, Shultz BB, Newman AP. Women's gymnastics injuries. A 5-year study. Am J Sports Med. 1993 Mar-Apr;21(2):271– 276.[PubMed] Snook GA. Injuries in women's gymnastics. A 5-year study. Am J Sports Med. 1979 Jul-Aug;7(4):242–244.[PubMed] Wadley GH, Albright JP. Women's intercollegiate gymnastics. Injury patterns and "permanent" medical disability. Am J Sports Med. 1993 Mar-Apr;21(2):314–320.[PubMed] Clarke KS, Buckley WE. Women's injuries in collegiate sports. A preliminary comparative overview of three seasons. Am J Sports Med. 1980 May-Jun;8(3):187–191.[PubMed]

Body movements on the men's competition mushroom: a three dimensional analysis of circular swings G Grassi, M Turci, Y Shirai, N Lovecchio, C Sforza, and V Ferrario Author information ► Copyright and License information ► 131

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Abstract Objectives: To develop a method for the three dimensional analysis of body movements and body positions during the performance of circular swings on the competition mushroom, an apparatus used by young gymnasts for pommel horse training.

Methods: Five experienced male gymnasts, all of national level, performed three series of 10 circular swings on the competition mushroom. An optoelectronic instrument was used for the detection of the three dimensional movement of 13 body landmarks. From landmark trajectories, several technical measurements were obtained: diameters of ideal circles of ankles, hips, shoulders; deviation of the ankle diameters from circularity and from the horizontal plane; angle between the shoulder, hip, and ankle. The values were used for a quantitative assessment of performance of the five gymnasts.

Results: During the exercise, each ankle should follow a nearly horizontal circular path (deviation from circularity ranged from 3.6% to 6%, deviation from horizontality was 9.4–19.7%), there should be an angle of about 180° at the hips (actual values 146–153°), and the shoulders should move as little as possible, and only in the lateral plane, without major anteroposterior movements (shoulder movement was 27–31% of ankle movement, hip movement was 16–20%).

Conclusions: The method could help coaches and gymnasts to determine which parts of the body are not repeating a selected movement with sufficient accuracy and to quantify improvements made after a specific training programme.

Full Text The Full Text of this article is available as a PDF (63K).

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Claessens AL, Lefevre J, Beunen G, Malina RM. The contribution of anthropometric characteristics to performance scores in elite female 132

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gymnasts. J Sports Med Phys Fitness. 1999 Dec;39(4):355– 360.[PubMed] Kerwin DG, Trewartha G. Strategies for maintaining a handstand in the anterior-posterior direction. Med Sci Sports Exerc. 2001 Jul;33(7):1182–1188.[PubMed] Davlin CD, Sands WA, Shultz BB. Peripheral vision and back tuck somersaults. Percept Mot Skills. 2001 Oct;93(2):465–471.[PubMed] King MA, Yeadon MR. Coping with perturbations to a layout somersault in tumbling. J Biomech. 2003 Jul;36(7):921– 927.[PubMed] Yeadon Maurice R, Brewin Mark A. Optimised performance of the backward longswing on rings. J Biomech. 2003 Apr;36(4):545– 552.[PubMed] Piccoli A, Brunani A, Savia G, Pillon L, Favaro E, Berselli ME, Cavagnini F. Discriminating between body fat and fluid changes in the obese adult using bioimpedance vector analysis. Int J Obes Relat Metab Disord. 1998 Feb;22(2):97–104.[PubMed] Sforza C, Turci M, Grassi G, Fragnito N, Pizzini G, Ferrario VF. The repeatability of choku-tsuki and oi-tsuki in traditional Shotokan karate: a morphological three-dimensional analysis. Percept Mot Skills. 2000 Jun;90(3 Pt 1):947–960.[PubMed] Sforza Chiarella, Turci Michela, Grassi Gian Piero, Shirai Yuri F, Pizzini Giuliano, Ferrario Virgilio F. Repeatability of mae-geri-keage in traditional karate: a three-dimensional analysis with black-belt karateka

Injury prediction in female gymnasts.

V A Steele and J A White Copyright and License information ► This article has been cited by other articles in PMC. Abstract In order to identify injury-proneness in female competitive gymnasts, 20 measures of flexibility, hypermobility, spinal posture and anthropometry were performed on 40 competitive gymnasts and injury scores were derived from the severity and extent of previous gymnastic injury and inherent hypermobility traits. Results were compared between contrasting groups of "low" and "high" injury gymnasts respectively (both N = 10). Nine variables 133

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demonstrated significant differences between the "low" and "high" injury risk status groups namely, weight (p less than 0.001), height (p less than 0.001), age (p less than 0.001), mesomorphy (p less than 0.01), Quetelet Index (p less than 0.01), shoulder flexion (p less than 0.05) and lumbar extension (p less than 0.05), standing lumbar curvature and total peripheral flexibility score (both p less than or equal to 0.05). Multiple regression analysis was applied to determine the relative contribution of these variables to the estimation of injury-proneness as evidenced by previous history of injury and hypermobility traits. Using 9 independent variables, multiple regression yielded a multiple correlation coefficient (R) = 0.840, accounting for over 70% of the observed variance (R2 = 0.706) in injury scores among the total group of gymnasts. However, a subset of five variables, (weight, mesomorphy, standing lumbar curvature, age and height) yielded a multiple correlation coefficient (R) = 0.834 accounting for almost 70% of the observed variance (R2 = 0.696). This was not significantly different from the larger subset. Using injury classification system of "low", "medium", and "high" risk categories, comparisons were made between predicted and observed injury scores in the respective risk categories. In "high" risk and "low" risk gymnasts, injury scores could be classified correctly with 70% and 79% accuracy respectively, so that relative risk status could be determined from simple physical tests which may be employed by practitioners in the field.

Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (620K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

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Beighton P, Horan F. Orthopaedic aspects of the Ehlers-Danlos syndrome. J Bone Joint Surg Br. 1969 Aug;51(3):444–453.[PubMed] Beighton P, Solomon L, Soskolne CL. Articular mobility in an African population. Ann Rheum Dis. 1973 Sep;32(5):413–418. [PMC free article][PubMed] CARTER C, WILKINSON J. PERSISTENT JOINT LAXITY AND CONGENITAL DISLOCATION OF THE HIP. J Bone Joint Surg Br. 1964 Feb;46:40–45.[PubMed] Garrick JG, Requa RK. Epidemiology of women's gymnastics injuries. Am J Sports Med. 1980 Jul-Aug;8(4):261–264.[PubMed] Goldberg MJ. Gymnastic injuries. Orthop Clin North Am. 1980 Oct;11(4):717–726.[PubMed] Heath BH, Carter JE. A modified somatotype method. Am J Phys Anthropol. 1967 Jul;27(1):57–74.[PubMed] Keys A, Fidanza F, Karvonen MJ, Kimura N, Taylor HL. Indices of relative weight and obesity. J Chronic Dis. 1972 Jul 1;25(6):329– 343.[PubMed] LEIGHTON JR. An instrument and technic for the measurement of range of joint motion. Arch Phys Med Rehabil. 1955 Sep;36(9):571– 578.[PubMed] Loebl WY. Measurement of spinal posture and range of spinal movement. Ann Phys Med. 1967 Aug;9(3):103–110.[PubMed] Lowry CB, Leveau BF. A retrospective study of gymnastics injuries to competitors and noncompetitors in private clubs. Am J Sports Med. 1982 Jul-Aug;10(4):237–239.[PubMed] Micheli LJ. Low back pain in the adolescent: differential diagnosis.

Am J Sports Med. 1979 Nov-Dec;7(6):362–364.[PubMed] Read MT. Stress fractures of the distal radius in adolescent gymnasts.

Br J Sports Med. 1981 Dec;15(4):272–276. [PMC free article][PubMed] Snook GA. Injuries in women's gymnastics. A 5-year study. Am J Sports Med. 1979 Jul-Aug;7(4):242–244.[PubMed] 141

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Sperryn PN. Ethics in sports medicine--the sports physician

Silent meniscal abnormalities in athletes: magnetic resonance imaging of asymptomatic competitive gymnasts C. N. Ludman, D. O. Hough, T. G. Cooper, and A. Gottschalk Copyright and License information â&#x2013;ş This article has been cited by other articles in PMC. Abstract BACKGROUND: Magnetic resonance imaging (MRI) produces exceptionally detailed images of the intra-articular structures of the knee.

Recognising the range of MRI appearances within a normal population is therefore necessary in order to avoid attributing a greater significance to these than is clinically justified. OBJECTIVE: To compare MRI appearances in asymptomatic gymnasts with those in a less active population in order to identify findings that may be seen in the absence of significant pathology and thereby aid the clinical management of this athletic group.

METHODS: MR images were obtained from 24 knees of asymptomatic competitive American collegiate gymnasts aged 18-22. The menisci were evaluated according to established grading criteria, and compared with a group of controls matched for age and sex. RESULTS: Grade 3 intrameniscal signal abnormalities are considered to be highly correlated with meniscal tears. When compared with control group, the experimental group of gymnasts had a significantly different distribution (p<0.001) of grade 3 intrameniscal signal changes, preferentially involving the lateral meniscus. The overall incidence of grade 3 changes (13%) in gymnasts was not, however, significantly different from the incidence in the controls.

CONCLUSIONS: A knowledge of these MRI appearances is important when evaluating the lateral menisci within this group of athletes to prevent unnecessary treatment or intervention. This is particularly pertinent when the imaging findings do not closely correlate with the site of symptoms.

Full Text The Full Text of this article is available as a PDF (80K).

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Crues JV, 3rd, Mink J, Levy TL, Lotysch M, Stoller DW. Meniscal tears of the knee: accuracy of MR imaging. Radiology. 1987 Aug;164(2):445–448.[PubMed] Stoller DW, Martin C, Crues JV, 3rd, Kaplan L, Mink JH. Meniscal tears: pathologic correlation with MR imaging. Radiology. 1987 Jun;163(3):731–735.[PubMed] De Smet AA, Norris MA, Yandow DR, Quintana FA, Graf BK, Keene JS. MR diagnosis of meniscal tears of the knee: importance of high signal in the meniscus that extends to the surface. AJR Am J Roentgenol. 1993 Jul;161(1):101–107.[PubMed] Watanabe AT, Carter BC, Teitelbaum GP, Seeger LL, Bradley WG., Jr Normal variations in MR imaging of the knee: appearance and frequency. AJR Am J Roentgenol. 1989 Aug;153(2):341– 344.[PubMed] Turner DA, Rapoport MI, Erwin WD, McGould M, Silvers RI. Truncation artifact: a potential pitfall in MR imaging of the menisci of the knee. Radiology. 1991 Jun;179(3):629–633.[PubMed] Peterfy CG, Janzen DL, Tirman PF, van Dijke CF, Pollack M, Genant HK. "Magic-angle" phenomenon: a cause of increased signal in the normal lateral meniscus on short-TE MR images of the knee. AJR Am J Roentgenol. 1994 Jul;163(1):149–154.[PubMed] Crues JV, 3rd, Ryu R, Morgan FW. Meniscal pathology. The expanding role of magnetic resonance imaging. Clin Orthop Relat Res. 1990 Mar;(252):80–87.[PubMed]

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