TY - JOUR
T1 - Impact of bone mineral density in reducing fracture risk in patients receiving alendronate plus alfacalcidol therapy
AU - Itoi, Eiji
AU - Uemura, Yukari
AU - Ohta, Hiroaki
AU - Nakamura, Toshitaka
AU - Fukunaga, Masao
AU - Orimo, Hajime
AU - Shiraki, Masataka
N1 - Funding Information:
The authors thank the investigators at all 186 facilities involved in this study. The authors also express sincere thanks to the members of the A-TOP research group, Dr. Yasuo Ohashi (Department of Integrated Science and Engineering for Sustainable Society, Chuo University), Dr. Takayuki Hosoi (Kenkoin Clinic), Dr. Satoshi Mori (Bone and Joint Surgery, Seirei Hamamatsu General Hospital), Dr. Toshitsugu Sugimoto (Internal Medicine 1, Shimane University Faculty of Medicine), Dr. Shiro Tanaka (Division of Clinical Trial Design and Management, Translational Research Center, Kyoto University), Dr. Shigeto Morimoto (Geriatric Medicine, Kanazawa Medical University), Dr. Akira Itabashi (Saitama Center for Bone Research, Kubojima Clinic), Dr. Toshihiko Yamashita (Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine), Dr. Itsuo Gorai (Department of Obstetrics and Gynecology, Hori Hospital), Dr. Hideaki Kishimoto (Department of Orthopedic Surgery, Nojima Hospital), Dr. Hideki Mizunuma (Department of Obstetrics and Gynecology, Hirosaki University School of Medicine), Dr. Naoto Endo (Division of Orthopedic Surgery, Niigata University Medical and Dental Hospital), Dr. Yoshiki Nishizawa (Osaka City University), and Dr. Kunio Takaoka (Hanwa Joint Reconstruction Center Hospital) for their help in the study design. We also express special thanks to Mr. Nobuaki Miyakawa (Public Health Research Foundation) for his help in preparing the manuscript, and to Ms. Akiko Ishizuka for her contributions to data management. The authors express sincere thanks to the Public Health Research Foundation, which supported the JOINT-02 study.
Funding Information:
The authors thank the investigators at all 186 facilities involved in this study. The authors also express sincere thanks to the members of the A-TOP research group, Dr. Yasuo Ohashi (Department of Integrated Science and Engineering for Sustainable Society, Chuo University), Dr. Takayuki Hosoi (Kenkoin Clinic), Dr. Satoshi Mori (Bone and Joint Surgery, Seirei Hamamatsu General Hospital), Dr. Toshitsugu Sugimoto (Internal Medicine 1, Shimane University Faculty of Medicine), Dr. Shiro Tanaka (Division of Clinical Trial Design and Management, Translational Research Center, Kyoto University), Dr. Shigeto Morimoto (Geriatric Medicine, Kanazawa Medical University), Dr. Akira Itabashi (Saitama Center for Bone Research, Kubojima Clinic), Dr. Toshihiko Yamashita (Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine), Dr. Itsuo Gorai (Department of Obstetrics and Gynecology, Hori Hospital), Dr. Hideaki Kishimoto (Department of Orthopedic Surgery, Nojima Hospital), Dr. Hideki Mizunuma (Department of Obstetrics and Gynecology, Hirosaki University School of Medicine), Dr. Naoto Endo (Division of Orthopedic Surgery, Niigata University Medical and Dental Hospital), Dr. Yoshiki Nishizawa (Osaka City University), and Dr. Kunio Takaoka (Hanwa Joint Reconstruction Center Hospital) for their help in the study design. We also express special thanks to Mr. Nobuaki Miyakawa (Public Health Research Foundation) for his help in preparing the manuscript, and to Ms. Akiko Ishizuka for her contributions to data management. The authors express sincere thanks to the Public Health Research Foundation , which supported the JOINT-02 study.
Funding Information:
Public Health Research Foundation (PHRF) sponsored the JOINT-02 study. PHRF receives financial support from the Japan Arteriosclerosis Prevention Fund, Teijin Pharma Ltd., Asahi Kasei Corporation, Takeda Pharmaceutical Company Ltd., GE Healthcare Japan, Toyo Medic Company Ltd., Banyu Pharmaceutical Company Ltd., and Dainippon Sumitomo Pharma Company Ltd.
Publisher Copyright:
© 2020 The Japanese Orthopaedic Association
PY - 2021/11
Y1 - 2021/11
N2 - Backgroud: Changes in bone mineral density (BMD) are a potential surrogate marker for fracture endpoints in clinical trials. However little is known whether the increase in BMD in response to combination treatment with alendronate plus alfacalcidol is associated with fracture risk reduction. We aimed to evaluate the impact of BMD on fracture risk in osteoporosis patients, using the data from the randomized clinical trial comparing alendronate plus alfacalcidol with alendronate alone. Methods: We selected 412 patients with two or more prevalent vertebral fractures and who had BMD measurements at baseline and after 6, 12, and/or 24 months out of 2022 patients from the database of the Japanese Osteoporosis Intervention Trial. Patients in this subset who received combination treatment with alendronate plus alfacalcidol had shown a lower risk of fracture than patients treated with alendronate alone. We used Poisson regression model analysis to calculate the proportion of treatment effect (PTE) that was attributable to BMD increases in patients receiving combination treatment. Results: The highest PTE attributable to changes in BMD was 1.2% in patients with a BMD increase of 3% or more in the lumbar spine. For BMD measurements of the radius, the highest PTE was 2.8% with a BMD increase of 0% or more. For BMD measurements of the metacarpal bone, the highest PTE was 1.2% with a BMD increase of 3% or more. In patients with a BMD greater than or equal to 70% of the young adult mean in the lumbar spine, the PTE attributable to BMD was 0.2%. In patients with a BMD greater than or equal to 70% of the young adult mean in the radius, the PTE attributable to BMD was 0.3%. Conclusions: The additional effects of alfacalcidol in reducing fracture risk do not likely result from increased BMD; other mechanisms remain a possibility.
AB - Backgroud: Changes in bone mineral density (BMD) are a potential surrogate marker for fracture endpoints in clinical trials. However little is known whether the increase in BMD in response to combination treatment with alendronate plus alfacalcidol is associated with fracture risk reduction. We aimed to evaluate the impact of BMD on fracture risk in osteoporosis patients, using the data from the randomized clinical trial comparing alendronate plus alfacalcidol with alendronate alone. Methods: We selected 412 patients with two or more prevalent vertebral fractures and who had BMD measurements at baseline and after 6, 12, and/or 24 months out of 2022 patients from the database of the Japanese Osteoporosis Intervention Trial. Patients in this subset who received combination treatment with alendronate plus alfacalcidol had shown a lower risk of fracture than patients treated with alendronate alone. We used Poisson regression model analysis to calculate the proportion of treatment effect (PTE) that was attributable to BMD increases in patients receiving combination treatment. Results: The highest PTE attributable to changes in BMD was 1.2% in patients with a BMD increase of 3% or more in the lumbar spine. For BMD measurements of the radius, the highest PTE was 2.8% with a BMD increase of 0% or more. For BMD measurements of the metacarpal bone, the highest PTE was 1.2% with a BMD increase of 3% or more. In patients with a BMD greater than or equal to 70% of the young adult mean in the lumbar spine, the PTE attributable to BMD was 0.2%. In patients with a BMD greater than or equal to 70% of the young adult mean in the radius, the PTE attributable to BMD was 0.3%. Conclusions: The additional effects of alfacalcidol in reducing fracture risk do not likely result from increased BMD; other mechanisms remain a possibility.
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U2 - 10.1016/j.jos.2020.10.017
DO - 10.1016/j.jos.2020.10.017
M3 - Article
AN - SCOPUS:85098189859
VL - 26
SP - 1085
EP - 1093
JO - Journal of Orthopaedic Science
JF - Journal of Orthopaedic Science
SN - 0949-2658
IS - 6
ER -