Abstract
Factors associated with an inadequate response (IR) to bisphosphonates have been reported in many countries, but not in Japan, where the approved dose is half the global dose. We analyzed factors associated with IR to risedronate in Japanese patients with osteoporosis. This was a post hoc analysis of 1261 Japanese osteoporosis patients who received risedronate for 1 year in phase III trials. IR was defined as more than one new vertebral fracture (VF) and/or negative change in lumbar spine bone mineral density (BMD) at 1 year. Various baseline and follow-up variables were examined for potential contribution to IR. Of the 1261 subjects, 118 exhibited an IR. At baseline, IR was associated with a higher BMD, lower levels of bone turnover markers (BTM) (serum bone-specific alkaline phosphatase, urinary N-terminal telopeptide of type 1 collagen and C-terminal telopeptide of type 1 collagen), and serum 25-hydroxyvitamin D [25(OH)D] below 16 ng/mL. BTM changes were blunted at 6 months in subjects with IR. On simple regression analysis, all the above variables and poor drug adherence were associated with an IR. On multivariate regression analysis, factors associated with IR were high BMD, vitamin D deficiency at baseline and low BTM at baseline, or a decreased BTM response at 6 months. Low serum 25(OH)D and BTM as well as high BMD at baseline were independent predictors of an IR to risedronate in Japan. These results emphasize the importance of the assessment of serum 25(OH)D and BTM in the management of osteoporosis with bisphosphonates.
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Acknowledgements
This study was supported by the Joint Development Program of EA Pharma Co., Ltd. and Takeda Pharmaceutical Co., Ltd. Funding for writing and editorial support was provided by EA Pharma Co., Ltd. This study was in part supported by the Research Program of Intractable Diseases provided by the Ministry of Health, Labour and Welfare of Japan. Pacific Edit reviewed the manuscript prior to submission.
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Dr. Ryo Okazaki received grants from Asahi-Kasei Pharma, Astellas Pharma, Chugai Pharmaceutical, Daiichi-Sankyo, EA Pharma, Eisai, Eli Lilly Japan, Ono Pharmaceutical, Taisho-Toyama Pharmaceutical, Takeda Pharmaceutical, and Teijin Pharma, outside of the submitted work. Mr. Ryoichi Muraoka and Mr. Masayuki Maehara received personal fees from EA Pharma Co. Ltd., during the course of the study. Dr. Daisuke Inoue received personal fees from EA Pharma, grants from Asahi-Kasei Pharma, Astellas Pharma, Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Eli Lilly Japan, Pfizer, Ono Pharmaceutical, Taisho-Toyama Pharmaceutical, Takeda Pharmaceutical, and Teijin Pharma, outside the submitted work.
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Okazaki, R., Muraoka, R., Maehara, M. et al. Factors associated with inadequate responses to risedronate in Japanese patients with osteoporosis. J Bone Miner Metab 37, 185–197 (2019). https://doi.org/10.1007/s00774-018-0931-2
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DOI: https://doi.org/10.1007/s00774-018-0931-2