Abstract
Eldecalcitol, a vitamin D3 analogue, significantly reduces the risk of new vertebral fractures and increases bone mineral density (BMD) more than does alfacalcidol. To determine the effect of eldecalcitol on the incidence of all fragility fractures caused by osteoporosis, we conducted post hoc analyses of the phase III clinical trial to evaluate the incidence of the osteoporotic fractures defined in the World Health Organization (WHO) Technical Report, and, also, the incidence of the major osteoporotic fractures utilized in the WHO Fracture Risk Assessment Tool (FRAX), and compared those in the eldecalcitol group with those in the alfacalcidol group. We also analyzed the incidence of osteoporotic fractures stratified by prespecified risk factors for fractures. Eldecalcitol treatment reduced the incidence of osteoporotic fractures defined by the WHO more than alfacalcidol treatment (18.6 % vs. 25.2 %; hazard ratio, 0.70; 95 % CI, 0.54–0.93). Prevalent vertebral fractures, two or more prevalent vertebral fractures, and total hip BMD T score less than −2.5 were the risk factors for new osteoporotic fractures with significant differences between the two treatments. Eldecalcitol also decreased the incidence of major osteoporotic fractures in the FRAX more than alfacalcidol (11.1 % vs. 16.3 %; hazard ratio, 0.66; 95 % CI, 0.46–0.94). In conclusion, treatment with eldecalcitol reduced the risk of fragility fractures caused by osteoporosis compared with alfacalcidol administration, which may result from a potent effect of eldecalcitol on BMD, bone structure, and bone turnover.
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References
Matsumoto T, Miki T, Hagino H, Sugimoto T, Okamoto S, Hirota T, Tanigawara Y, Hayashi Y, Fukunaga M, Shiraki M, Nakamura T (2005) A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 90:5031–5036
Matsumoto T, Ito M, Hayashi Y, Hirota T, Tanigawara Y, Sone T, Fukunaga M, Shiraki M, Nakamura T (2011) A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures: a randomized, active comparator, double-blind study. Bone (NY) 49:605–612
Kanis JA, on behalf of the World Health Organisation Scientific Group (2007) Assessment of osteoporosis at the primary health care level. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield
Kanis JA, Oden A, Johnell O, Jonsson B, De Laet C, Dawson A (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12:417–427
Raisz LG (2008) Overview of pathogenesis. In: Rosen CJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 7th edn. American Society for Bone and Mineral Research, Washington, DC, pp 203–206
Raisz LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115:3318–3325
Ito M, Nakamura T, Fukunaga M, Shiraki M, Matsumoto T (2011) Effect of eldecalcitol, an active vitamin D analog, on hip structure and biomechanical properties: 3D assessment by clinical CT. Bone (NY) 49:328–334
Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA III, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 4:721–739
Kanis JA, Johnell O, De Laet C, Johansson H, Oden A, Delmas P, Eisman J, Fujiwara S, Garnero P, Kroger H, McCloskey EV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone (NY) 35:375–382
Robinson CM, Royds M, Abraham A, McQueen MM, Court-Brown CM, Christie J (2002) Refractures in patients at least forty-five years old: a prospective analysis of twenty-two thousand and sixty patients. J Bone Joint Surg Am 84A:1528–1533
Center JR, Bliuc D, Nguyen TV, Eisman JA (2007) Risk of subsequent fracture after low-trauma fracture in men and women. JAMA 297:387–394
Acknowledgments
The present study was sponsored by Chugai Pharmaceutical Co., Ltd. The sponsor of the study participated in the design of the study, data collection, data analyses, data interpretation, and writing of the report. The sponsor supplied the study medication and had responsibility for data collection and quality control. The corresponding author had full access to all the data in the study and had responsibility for the decision to submit for publication. The authors thank all the investigators who participated in the eldecalcitol phase III clinical trial.
Conflict of interest
T.N. has received consulting fees (Asahi Kasei Pharma, Astellas, Banyu, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Ono, Takeda, Teijin Pharma) and belongs to the Japan Ministry of Health, Welfare and Labour as a councilor for hospital administration and social medical insurance. T.T. is a full-time employee of Chugai Pharmaceutical Co., Ltd. M.F. is a member of an advisory council (Asahi Kasei Pharma, Astellas). M.S. has received consulting fees (Asahi Kasei Pharma, Astellas, Chugai, Daiichi Sankyo, MSD, Teijin Pharma) and lecture fees (Eisai, Ono). T.M. is a member of an advisory board (Lilly) and has received consulting fees (Asahi Kasei Pharma, Astellas, Chugai, Daiichi Sankyo, Ono, Teijin Pharma).
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Nakamura, T., Takano, T., Fukunaga, M. et al. Eldecalcitol is more effective for the prevention of osteoporotic fractures than alfacalcidol. J Bone Miner Metab 31, 417–422 (2013). https://doi.org/10.1007/s00774-012-0418-5
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DOI: https://doi.org/10.1007/s00774-012-0418-5