Bone Metabolism & Osteoporosis Symposium

S2-1 Prof. Toshio Matsumoto, M.D.

Personal Information

Nationality: Japan

Position: Director

Department: Fujii Memorial Institute of Medical Sciences

Organization: Tokushima University

Email: toshio.matsumoto@tokushima-u.ac.jp

Educational background & professional experience (in sequence of the latest year)

1974 University of Tokyo School of Medicine MD degree 1978-1981 Yale University School of Medicine Research Fellow 1996-2014 Department of Medicine & Bioregulatory Sciences, Tokushima University Graduate School of Medical Sciences Professor and Chair

Research Interests

1 Regulatory mechanism of osteoblast differentiation and bone formation 2 Mechanism of development of cancer-associated bone disease 3 Roles of endocrine and other systems in the development of atherosclerosis

Publications (5 important publications – latest sequence)

1.Dong B, Endo I, Ohnishi Y, Kondo T, Hasegawa T, Amizuka N, Kiyonari H, Shioi G, Abe M,

Fukumoto S, Matsumoto T. Calcilytic ameliorates abnormalities of mutant calcium-sensing receptor knock-in mice mimicking autosomal dominant hypocalcemia (ADH). J Bone Miner Res 2015;61:727-33, 2.Yoshida S, Aihara K, Ikeda Y, Sumitomo-Ueda Y, Uemoto R, Ishikawa K, Ise T, Yagi S, Iwase T,

Mouri Y, Sakari M, Matsumoto T, Takeyama K, Akaike M, Matsumoto M, Sata M, Walsh K, Kato

S, Matsumoto T. Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling. Circulation 2013; 128:60-71 3.Aihara K, Azuma H, Akaike M, Ikeda Y, Sata M, Takamori N, Yagi S, Iwase T, Sumitomo Y,

Kawano H, Yamada T, Fukuda T, Matsumoto T, Sekine K, Sat T, Nakamichi Y, Yamamoto Y,

Watanabe T, Nakamura T, Oomizu A, Tsukada M, Hayashi H, Sudo T, Kato S, Matsumto T. Straindependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice. J Clin Invest 2007;117:1486-1489 4.Oshima T, Abe M, Asano J, Hara T, Kitazoe K, Sekimoto E, Tanaka Y, Shibata H, Hashimoto T,

Ozaki S, Kido S, Inoue D, Matsumoto T. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood 2005;106: 3160-3165. 5.Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, Kawakami T, Arioka K, Sato

H, Uchiyama Y, Masushige S, Fukamizu A, Matsumoto T, Kato S. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning.

Nature Genet 1997; 16:391-396

S2-1 Role of Active Vitamin D Compounds in the Treatment of Osteoporosis

TOSHIO MATSUMOTO

Fujii Memorial Institute of Medical Sciences, University of Tokushima, Tokushima, Japan,

In order to maintain bone remodeling balance, it is important to keep enough Ca absorption. Vitamin D is required to enhance Ca absorption from the gut, but native vitamin D cannot exert its full effect and vitamin D has to be activated to 1,25-dihydroxyvitamin D [1,25(OH)2D] in the kidney to develop its effects. Renal impairment is the main cause of deterioration of the activation of vitamin D. Chronic kidney disease (CKD) develops with aging, causing a reduction in the renal 1,25(OH)2D production and intestinal Ca absorption. Such changes in the elderly cause negative Ca balance, and play a significant role in the pathogenesis of osteoporosis. Therefore, almost all the therapeutic drugs for osteoporosis are accompanied by vitamin D and Ca supplementation in clinical trials. However, because of the poor activation of vitamin D in the elderly, it is more plausible to supply with active vitamin D compounds. In addition, Ca supplementation causes a transient rise in serum Ca, which is associated with an increase in vascular calcification and cardiovascular event. Especially when Ca supplements are given with active vitamin D, excess Ca is absorbed, causing hypercalcemia, hypercalciuria and renal impairment. Thus, Ca supplementation is not recommended with active vitamin D.

Among active vitamin D compounds, eldecalcitol increases bone mass and strength by reducing osteoclast formation and bone resorption with an increase in focal bone minimodeling in animals. A 3-year randomized, double-blind, clinical trial demonstrated that eldecalcitol reduces the incidence of vertebral and wrist fractures more strongly than alfacalcidol. The marked reduction in wrist fractures is suggestive of the effect in increasing muscle power and preventing falls. Further studies are needed to clarify its effect on muscle strength and falls.

S2-2 Siok Bee Chionh, MBBCh BAO

Personal Information

Nationality: Singaporean Position: Senior Consultant & Asst Prof (please see below) Department: Division of Endocrinology, University Medicine Cluster Organization: National University Hospital & National University of Singapore Email: Siok_Bee_Chionh@nuhs.edu.sg

S2-2 Is It Osteoporosis?

SIOK BEE CHIONH

Division of Endocrinology, National University Hospital & National University of Singapore

An update will be given on the new criteria proposed by the National Bone Health Alliance Working Group for the clinical diagnosis of Osteoporosis in USA1, and expands on the current definition of Osteoporosis as a BMD T-score of -2.5 or less. This position paper has been endorsed by the Endocrine Society (USA), the American Society of Bone and Mineral Research and the American Academy of Orthopedic Surgeons, and is expected to be incorporated in the next NOF Clinician’s Guide.

In addition, case studies will be used to illustrate that not all cases of Osteoporosis are straightforward post-menopausal or age-related Osteoporosis. There may be secondary or contributory causes to the Osteoporosis, or there may be other causes of low bone mass and fractures, such as Osteomalacia and CKD-Mineral Bone Disease. These additional factors must be addressed for the patient to improve their overall fracture risk.

1Sirius ES et al (2014) The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int 25:1439-1443

S2-3 Jung-Fu Chen, M.D.

Personal Information

Nationality: Taiwan

Position: Chief

Department: Department of Endocrinology and Metabolism

Organization: Kaohsiung Chang Gung Memorial Hospital

Email: 0722cjf@adm.cgmh.org.tw

Educational background & professional experience (in sequence of the latest year)

2015-NOW Department of Endocrinology and Metabolism of Chang Gung Memorial Hospital at Kaohsiung Chief 2013-2015 Department of Internal Medicine of Chang Gung Memorial Hospital at Kaohsiung Vice Chief 2009-2013 Department of Health Examination of Chang Gung Memorial Hospital at Kaohsiung Chief

Research Interests

1. Thyroid 2.DM 3. Osteoporosis

Publications (5 important publications – latest sequence)

1.Chen JF, Yang KH, Zhang ZL, Chang HC, Chen Y, Sowa H, Gürbüz S. A systematic review on the use of daily subcutaneous administration of teriparatide for treatment of patients with osteoporosis at high risk for fracture in Asia. Osteoporos Int. 2014 Aug 20. 2.Hwang JS, Tsai KS, Cheng YM, Chen WJ, Tu ST, Lu KH, Hou SM, Yang SH, Cheng H, Lai HJ,

Lei S, Chen JF*. Vitamin D status in non-supplemented postmenopausal Taiwanese women with osteoporosis and fragility fracture. BMC Musculoskeletal Disorders. 2014 Jul 28;15:257. 3.Hwang JS, Liou MJ, Ho C, Lin JD, Huang YY, Wang CJ, Tsai KS, Chen JF*. The effects of weekly alendronate therapy in Taiwanese males with osteoporosis. J Bone Miner Metab. 2010

May;28(3):328-33. 4.Loke SS, Yang KD, Chen KD, Chen JF. Erosive esophagitis associated with metabolic syndrome, impaired liver function, and dyslipidemia. World J Gastroenterol. 2013 Sep 21;19(35):5883-8. 5.Hwang JS, Chan DC, Chen JF, Cheng TT, Wu CH, Soong YK, Tsai KS, Yang RS. Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: summary. J Bone Miner

Metab. 2014 Jan; 32(1): 10-6.

S2-3 Osteoporosis and Diabetes

JUNG FU CHEN

Department of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital

Today Diabetes mellitus has eventually become a medical mass phenomenon in majority parts of the world. Affluent access to a high-carbohydrate/high-fat diet in combination with denser energy uptake has led to a pandemic of the metabolic syndrome and T2DM .Rationally vascular complications include nephropathy, neuropathy and retinopathy as well as ischemic heart disease, peripheral vascular disease and stroke. Now novelty diabetes related osteoporotic fractures becomes as a newly but lonely ignored diabetic complication. Using Taiwan’s National Health Insurance Research Database (2000–2008), It did showed during 652,530 person-years of follow-up, there were 12,772 newly diagnosed fracture cases. The incidences of for people with diabetes and without were 24.2 and 17.1 per 1,000 person-years, respectively (P < 0.0001). Compared with people without diabetes, the adjusted HR of was 1.66 for people with diabetes. The ORs of post deep wound infection, septicemia, and mortality associated with diabetes were 1.34 , 1.42 ,and 1.27 respectively.

Generally Hip risk is significantly increased in both type 1 (RR 6.3) and type 2 (RR 1.7) diabetes. Type 1 diabetes with poor control is dually associated with severe osteoporosis, but in type 2 diabetes, an increased risk of hip fracture is seen despite higher BMD. In some large observational studies showed femoral neck BMD T-score and derived the WHO Risk Assessment Tool (FRAX) score were precisely associated with hip and no spine fractures. But the application of FRAX in diabetics can’t really assess and do under-estimate the ominous diabetes related fracture .Prevention strategies for people with diabetes are just the same as for the general population and include adequate vitamin D and calcium supplementation with regular aerobic weight loading exercise. For patients with type 2 diabetes with fracture risk factors, thiazolidinediones and sodium–glucose cotransporter 2 inhibitors should be avoided possibly as revealing associated with a higher risk of fracture and also current antiosteoporotic fracture agents are given as indicated.