Efficacy and safety of once-monthly risedronate in osteoporosis subjects with mild-to-moderate chronic kidney disease: a post hoc subgroup analysis of a phase III trial in Japan
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Limited data are available on the safety and efficacy of anti-resorptive agents, particularly once-monthly bisphosphonates, for use in osteoporotic patients with chronic kidney disease (CKD). We conducted a post hoc analysis of data from a 12-month, randomized, double-blind, phase III study to evaluate the safety and efficacy of once-monthly risedronate (RIS-OM) 75 mg tablets in Japanese osteoporosis patients with mild-to-moderate CKD. Patients who received RIS-OM 75 mg were stratified by baseline estimated glomerular filtration rate (eGFR; ≥ 90, ≥ 60 to < 90, or ≥ 30 to < 60 mL/min/1.73 m2). Safety endpoints were incidence of adverse events (AEs) and percent change from baseline in eGFR, serum creatinine, calcium, and phosphorus. Efficacy endpoints were percent change from baseline in lumbar spine bone mineral density (BMD) and bone turnover markers (BTMs). In 420 patients included (age 67.7 ± 6.7 years, women 98.8%), the incidence of all AEs, gastrointestinal disorders, acute phase reaction, non-vertebral fractures, and renal and urinary disorders was not significantly different among subgroups. Interaction between subgroups and time was significant for eGFR (p = 0.010) and serum creatinine (p = 0.001) but considered to be regression to the mean and clinically insignificant. BMD significantly increased while BTMs significantly decreased from baseline with a similar degree of change among the subgroups. In conclusion, RIS-OM 75 mg showed consistent safety and efficacy in suppressing bone turnover and increasing BMD in Japanese primary osteoporosis patients with mild-to-moderate CKD. These results should, however, be interpreted with caution because the number of patients with moderate CKD was limited.
KeywordsBisphosphonate Chronic kidney disease eGFR Once-monthly risedronate Renal safety
This study was supported by the Joint Development Program of EA Pharma Co., Ltd. and Takeda Pharmaceutical Co., Ltd. Medical writing services were provided by Mami Hirano, MS, of Cactus Communications, and funded by EA Pharma Co., Ltd. Support for statistical analysis was provided by Ryoichi Muraoka, DVM, of Asklep, and funded by EA Pharma Co., Ltd.
TSu, DI (guarantor), TSh, and YN designed the study. MM designed the study and contributed to the conduct of the study and data acquisition and interpretation. IO was responsible for statistical analysis and data interpretation. All authors critically reviewed the paper for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions related to the accuracy and integrity of the paper will be investigated and properly resolved.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
Dr. Toshitsugu Sugimoto has received research grants from Eli Lilly Japan, Taisho Toyama Pharmaceutical, Chugai Pharmaceutical, Daiichi-Sankyo Co., Astellas Pharma, and Eisai, as well as consulting fee from Asahi-Kasei Pharma Co. Dr. Daisuke Inoue reports personal fees from EA Pharma and grants from Astellas Pharma, Asahi-Kasei Pharma, Chugai Pharmaceutical, Daiichi-Sankyo Co., EA Pharma, Eli Lilly Japan, Eisai, Pfizer, Ono Pharmaceutical, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical, and Teijin Pharma, outside the submitted work. Mr. Masayuki Maehara and Mr. Ichiro Oikawa are full-time employees of EA Pharma. Dr. Takashi Shigematsu has received consultant fees from EA pharma and Takeda pharmaceutical. Dr. Yoshiki Nishizawa has no conflicts of interest to disclose.
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