Musculoskeletal Complication of Diabetes by PAINWeek

Musculoskeletal Complication of Diabetes Ronald J. Rapoport, MD

Disclosure  Grant/Research Support: Astra-Zeneca, Abbott  Speaker's Bureau: Abbott, Amgen, Forest, Pfizer, Lilly, UCB

Learning Objectives ď&#x201A;§ List musculoskeletal disorders associated with diabetes mellitus (DM) ď&#x201A;§ Describe signs and symptoms of DM-related joint disease

ď&#x201A;§ Diabetes mellitus is a chronic metabolic condition characterized by persistent hyperglycemia with resultant morbidity and mortality related primarily to its associated microvascular and macrovascular complications.

Smith L, Burnet S, McNeil J. Musculoskeletal manifestations of diabetes mellitus . Br J Sports Med 2003;37:30-35

ď&#x201A;§ Diabetes mellitus (DM) is associated with a several musculoskeletal disorders. The incidence of DM and the life expectancy of the diabetic patient have both increased, resulting in the increased prevalence and clinical importance of musculoskeletal alterations in diabetic subjects. The exact pathophysiology of most of these musculoskeletal disorders remains obscure. Connective tissue disorders, neuropathy, vasculopathy or combinations of these problems, may underlie the increased incidence of musculoskeletal disorders in DM.

ď&#x201A;§ The development of musculoskeletal disorders is dependent on age and the duration of DM; however, it has been difficult to show a direct correlation with the metabolic control of DMâ&#x20AC;Ś..No specific treatment is available, and treatments used in the general population are also recommended for diabetic subjects.

Arkilla P, Gautier J, Musculoskeletal disorders in diabetes mellitus: an update. Best Prac & Res Clin Rheum 2003;17 no 6: 945-970

Syndromes of Limited Joint Mobility  Diabetic hand syndrome(diabetic cheiroarthropathy)  Adhesive capsulitis (frozen shoulder)  Trigger finger (flexor tenosynovitis)  Dupuytren’s contracture –Osteoporosis –Diffuse idiopathic skeletal hyperostosis (DISH)

Neuropathies  Neuropathic arthritis (Charcot’s joints)  Carpal tunnel syndrome  Diabetic amyotrophy  Reflex sympathetic dystrophy  Diabetic muscle infarction

Diabetic hand syndrome (DHS)  Biochemical abnormalities include:  non-enzymatic glycosylation of collagen protein.(3)  increased cross linking of collagen and consequent resistance to enzymatic degradation. (4)  Altered collagen synthesis(5)  Increased formation of advanced glycosylation end products(6) (3)Vishwanath V, Frank KE, Elments CA. Glycation of skin collagen in type 1 diabetes mellitus: correlation with long-tem complications. Diabetes 1986; 35: 916-921 (4)Chang K, Uitto J, Rowald EA. Increased collagen cross-linkages in experimental diabetes. Diabetes 1980;29:778-781 (5)Kohn RR, Hensse S. Abnormal collagen in cultures o fibroblasts from human beings with diabetes mellitus. Biochem and biophys Res Comm 1977;76: 365-371. (6)Kennedy L & Lyons TM. Non-enzymatic glycation. Br Med Bull 1989;445: 174-190.

Diabetic Hand Syndrome (DHS)  Patients complain of stiffness, loss of dexterity and weakness.  DHS is painless and is usually not disabling enough to make a patient seek treatment.  Prevalence of between 8 and 58% in type 1 DM, and 25 to 76% in type 2.(7)  No effect by sex , but association with duration of DM and age well established.(8)  No association with degree of metabolic control.(8) (7) Starkman HS, Gleason RE, Rand LI et al. Limited joint mobility of the hand in patients with diabetes mellitus: relation to chronic complications Annals Rheum Dis.1986:45: 130-135 (8) Skenik S, Weitzman, Buskila D. Limited joint mobility and other rheumatologic manifestation in diabetic patients .Diabetes Metab.1987;13:187-92

 DHS is characterized by thick, tight, waxy skin mainly on the dorsal aspect of the hands, with flexion deformities of the metacarpophalangeal and interphalangeal joints (increased resistance to passive extension of the joints). This can be shown clinically by the inability of the two palms to come completely together, with the wrists flexed and fingers fanned. Thus the patient may exhibit the ‘prayer sign’.(1)  May be associated with an increased risk of complications such as proliferative retinopathy and neuropathy. (9) (9) Gauri LA, Q Fatima. Musculoskeletal manifestations of diabetes mellitus. J Ind Med Assoc. 2009;107: 810-820.

Diabetic Hand Syndrome (DHS)

Adhesive Capsulitis (Frozen Shoulder)  Perhaps the most disabling of the common musculoskeletal disorders associated with DM and characterized by painful loss of shoulder motion usually starting with a limitation of abduction and external rotation.(10)  Incidence of 3-5% in the general population and tends to affect females in their fifth or sixth decade of life. (11)  Typically affects the non-dominant shoulder and 6-17% of patients will have involvement of the other shoulder once the first has resolved. (12)  Prevalence in diabetics ranges from 4-29% and found in those with longer standing disease, usually type 1, and commonly involves both shoulders.(13)  It may be associated with other findings associated with limited joint mobility such as DC and DHS. (13) 10) Neviaser RJ, Neviaser TJ. The frozen shoulder, diagnosis and management. Clin Orthop Relat Res 1987;223: 59-64. (11)Dias R, Cutts S, Massoud S. Frozen shoulder. Br Med J 2005;331: 1453-6. (12)Rizk TE, Pinals R. Frozen shoulder. Semin Arth Rheum 1982;11:440-52. (13)Balci M, Balci MK, Tuzuner S. Shoulder adhesive capsulitis and shoulder range of motion in type2 DM: association with diabetic complications. J Diab Comp 1999;13:135-40.

 It usually involves three stages: – Painful freezing phase lasting 10-36 weeks with pain worse at night and poor response to NSAIDs.

 Adhesive stage of 4-12 months duration where pain gradually subsides and is usually found only with extreme movements although stiffness persists and is characterized by near total loss of external rotation.  Resolution phase lasts 12-42 months and is noted by spontaneous improvement (11)

 Diagnosis made clinically. Lab tests not helpful and X-ray, ultrasound, MRI, etc. may help rule out other entities.  In early phases both synovial and capsular thickening are noted while in later stages only capsular thickening observed.(12)  Approach to treatment varies and includes PT, oral or intra-articular corticosteroids, NSAIDs..and ? Manipulation under general anesthesia.  Important to emphasize that a return to full ROM may not be possible.

12) Sofka CM, Ciavarra GA,Hannafin JA,Cordasco FA, Potyter HG. MRI imaging of adhesive capsulitis: correlation with clinical staging.HSS J2008;4:164-9.

Adhesive Capsulitis (frozen shoulder)

Dupuytren’s contractures  DC are a spontaneous occurring chronic and idiopathic thickening of the palmar aponeurosis leading to various degrees of flexion deformity of the fingers.(13)  In patients with DM the 3rd and 4th fingers are commonly affected compared with the 5th fingers in the general population.(14)  The prevalence of DC in patients with DM ranges from 20-63%, compared with 13% in the control group .(14)  Among patients with DCs 13-39% have DM.(14)

Dupuytren’s contractures  Treatment includes PT, glycemic control, and surgery if necessary.  Most often the contractures do not require surgical intervention.(15)

Dupuytrenâ&#x20AC;&#x2122;s

Charcot joint (neuropathic arthropathy)  Defined as a progressive, destructive arthropathy in an area of sensory loss.(16)  It occurs in 0.1-5% of diabetic patients and most frequently involves the tarsal and tarsometatarsal joints but may also involve other weight bearing joints such as the ankles and knees(17)  2/3 of patients have type 2 DM and men and women are equally affected.  The incidence increases with the duration of DM and in the 50-69 year old group.(16)  Initial diagnosis often clinical based upon unilateral swelling, increased skin temperature, joint effusion and instability. It may mimic septic arthritis.(18)  X-ray finding disclose a destructive arthropathy, but the patient’s symptoms are usually milder than one would expect based upon the radiographic findings.  There are two theories of the etiology: one is the neurotraumatic theory that states the changes result from repeated mechanical trauma to a joint that is insensitive to pain. The second is the neurovascular theory that states that the changes result from a neurally initiated vascular reflex that leads to hyperemia and active bone resorption.(19)  Treatment difficult-but early diagnosis allows intervention such as better control of DM, rest and relief of pressure and attention to any ulcer formation (16)Collange C & Burde MA. Muscloskeletal problems of neurogenic origin. Best Prac and Res Clin Rheum 2000;14:325-43. (17)Sinha S, Munichoodappa CS & Koak GP. Neuro-arthropathy in diabetes mellitus. Med 1972;51:191-210. (18)Balint GP, Korda J, Hangody L & Balint PV. Foot and ankle disorders. Best Prac and Clin Res Rheum 2003;17:87-111 (19)Nigrisoli M, Moscato M & Padovani G Syringomyelic arthropathy: a description of two cases and a review of the literature. La Chir Org Di Movim 1991;76: 237-44.

Charcot joint

Carpal tunnel syndrome  A disorder characterized by paresthesia over the cutaneous distribution of the median nerve, involving the 1st through 3rd fingers and the radial side of the 4th. It is typically worse at night.(20)  Symptoms may be a result of compression of the median nerve in the carpal tunnel, diabetic neuropathy, or a combination of both.(20)  CTS is common in diabetics with an incidence of 11-16%, and about 5-8% of patients with CTS have DM.(21)  Treatment similar in those with and without DM after diagnosis established. (20) Jung Y, Hohmann TC, Gerneth JA. Diabetic hand syndrome. Metab 1971;20:1008-15. (21)Comi G, Lozza L, Galgardi G et al. Presence of carpal tunnel syndrome in diabetics: effect of age ,sex, diabetes duration and neuropathy. Acta Diabet Lat 1985;22: 259-62.

Carpal tunnel syndrome

Diffuse idiopathic skeletal hyperostosis  DISH is characterized by exuberant new bone formation usually in the thoracic and lumbar spine.  New bone appears to ‘flow’ from one vertebral body to the next and is usually found on the right side of the thoracic vertebrae…except if the patient has situsinversus or dextrocardia. Ossification of ligaments and tendons elsewhere may be found.  Proposed etiology involves the prolonged high levels of insulin and/or insulin-like growth factors stimulating new bone growth.(22)  Symptoms usually begin insidiously and painlessly and is often discovered as an incidental X-ray finding. Later back pain and stiffness may be seen-but not nearly as severe as that seen in ankylosing spondylitis.(23)  Prevalence is 13-49% in diabetics and 2-13% in the normal population. (24)  Despite the impressive changes on X-ray, there is limited narrowing of intervertebral discs and less changes of classic OA than would be expected.  Treatment is conservative.   

(22)Forgacs SS. Diabetes mellitus and rheumatic disease. Clin Rheu Dis 1986;12:729-53. (23)Gray RG & Gottlieb NL. Rheumatic disorders associated with diabetes.: literature review. Sem in A&R 1976;6:19-34. (24)Kiss C, Szilagy M, Paksy A et al.Risk factors for DISH: a case controlled study. Rheum 2002;41:27-30.

Diffuse idiopathic skeletal hyperostosis

Diabetic Amyotrophy  A disabling illness distinct from other forms of diabetic neuropathy.  Characterized by muscle wasting, and by diffuse lower limb muscle pain, and asymmetrical loss of deep tendon reflexes. The shoulder girdle less commonly affected.(25)  It typically is found in older men with type 2 DM and is often associated with weight loss which may reach as high as 40% of the pre-morbid state.(25)  Most cases improve with conservative care such as PT and diabetic control, but the improvement is gradual and usually incomplete.(25)



(25)Sander HW, Chokroverty S. Diabetic amyotrophy: current concepts. Semin Neur 1966;16:173-8.

Diabetic Amyotrophy

ď&#x201A;§ The prevalence and socio-economic burden of DM is increasing at an alarming rate. Not only is the incidence increasing, but the diagnosis is occurring in a younger population. While macrovascular disease is the predominant cause of disability amongst patients with DM, the contribution of non-vascular functional impairment should not be overlooked. (26) ď&#x201A;§ The prevalence of the musculoskeletal complications of DM are numerous and pose both a diagnostic and therapeutic challenge. (26)Gauri LA, Fatima Q. J Ind Med Assoc.2009;107:810-21.