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

摘要

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) 75mg tablets in Japanese osteoporosis patients with mild-to-moderate CKD. Patients who received RIS-OM 75mg were stratified by baseline estimated glomerular filtration rate (eGFR; 90, 60 to< 90, or 30 to< 60mL/min/1.73 m(2)). 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 +/- 6.7years, 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 75mg 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.