Abstract
The aim of osteoporosis treatment is to prevent future fractures. Although concurrent treatment has been used very frequently for osteoporosis in clinical practice, there are no data on accurate and verified effectiveness of concurrent treatment for fracture prevention in patients with osteoporosis. To clarify the clinical usefulness of concurrent treatment, the Japan Osteoporosis Society has authorized the establishment of the A-TOP (Adequate Treatment of Osteoporosis) research group. The objective of this research is to establish a design for a clinical trial to prove whether concurrent treatment using both alfacalcidol (1-alpha-hydroxycholecalciferol) and alendronate is more effective as compared to treatment using alendronate alone in terms of fracture prevention. The present study was named JOINT (Japanese Osteoporosis Intervention Trial) and is based on a method using national, prospective, randomized, open-labeled, blinded endpoints focusing on postmenopausal osteoporosis with a high risk for fracture. The patients were mainly selected by practitioners and allocated randomly by a central registration system into two groups, of which one received 5 mg/day of alendronate alone, and the other received 1 μg/day of 1-alpha-hydroxycholecalciferol (alfacalcidol) in addition to the alendronate. The endpoints focused primarily on fracture prevention, and the patients’ quality of life (QOL) and change in body height, as well as adherence and the adverse events of the treatments were evaluated secondarily. To obtain sufficient statistical power in the events during a 2-year observation period, the patients who are expected to have higher risk were selected to participate in this study, and it was decided that the final plan would involve 890 patients per group (two-sided alpha = 0.05, power = 0.8). Data collection began in November 2003. Correspondence regarding the registration of the investigator and the progress of the study was conducted through a web system from the Public Health Research Foundation to practitioners.
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Acknowledgments
The authors express thanks to the chairman (Dr. Rikushi Morita) and the members of the ethics committee: Ms. Mamiko Matsumura, Dr. Tetsuro Inoue, Dr. Isao Yoshimura, Dr. Mitsuyoshi Nakajima, Tooru Ebihara, R.Ph., Mr. Shinya Hattori and Mr. Kousaku Uchida. This JOINT study was sponsored by the Public Health Research Foundation. The authors would like to thank those who participated as clinical investigators in JOINT-02. The authors also thank the Japan Arteriosclerosis Prevention Fund, Teijin Pharma Limited, Asahi Kasei Corporation, Takeda Pharmaceutical Company Limited, GE Healthcare Japan, Toyo Medic Co., Ltd., Banyu Pharmaceutical Co., Ltd., and Dainippon Sumitomo Pharma Co., Ltd., for their generous donations.
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For the A-TOP (Adequate Treatment of Osteoporosis) Research Group.
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Shiraki, M., Kuroda, T., Miyakawa, N. et al. Design of a pragmatic approach to evaluate the effectiveness of concurrent treatment for the prevention of osteoporotic fractures. J Bone Miner Metab 29, 37–43 (2011). https://doi.org/10.1007/s00774-010-0188-x
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DOI: https://doi.org/10.1007/s00774-010-0188-x