Efficacy, tolerability and safety of once-monthly administration of 75 mg risedronate in Japanese patients with involutional osteoporosis: A comparison with a 2.5 mg once-daily dosage regimen

Oral risedronate has been shown to be effective in the treatment of osteoporosis when administered once-daily or once-weekly in Japan. This randomized, double-blind, multicenter 12-month study was conducted to compare the efficacy and tolerability of oral risedronate 75 mg once-monthly with 2.5 mg once-daily in Japanese patients with involutional osteoporosis. Bone mineral density (BMD), biochemical markers of bone metabolism, fractures, and adverse events (AEs) were evaluated. At the end of the study (Month 12, last observation carried forward [M12, LOCF]), mean percent change (SD) from baseline in lumbar spine (L-2-L-4) BMD, measured by dual energy X-ray absorptiometry (primary endpoint), was increased by 5.69 (4.00)% in the 2.5 mg once-daily group (n = 428), and 5.98 (4.54)% in the 75 mg once-monthly group (n = 422). In the non-inferiority t-test (non-inferiority margin Delta = 1.5%), the 75 mg once-monthly group was non-inferior to the 2.5 mg once-daily group (p < 0.0001). The difference between treatment groups was 0.28% (95% CI, 0.31% to 0.88%). Changes in biochemical markers of bone metabolism were generally comparable in the two groups, although decreases in the percent change from baseline in urinary NTX/CRN and CTX/CRN were statistically greater in the 2.5 mg once-daily group than the 75 mg once-monthly group. The frequency of new vertebral fractures (including aggravation of prevalent fractures) at the end of the study (M12, LOCF) was also similar in the two groups: 1.2% in the 2.5 mg once-daily group and 1.3% in the 75 mg once-monthly group. The incidence of mild/moderate/severe AEs was 75.5%/63%/0.5% in the 2.5 mg once-daily group and in the 75 mg once-monthly group. AEs associated with gastrointestinal symptoms occurred in approximately 80% of subjects in each group but with no severe cases. AEs potentially associated with acute phase reaction (including symptoms of influenza-like illness or pyrexia starting within 3 days of the first dose of the study drug and with a duration of 7 days or less) only occurred in the 75 mg once-monthly group (2.1%, 9/422 subjects; influenza-like symptoms in 1 subject and pyrexia in 8 subjects), although the incidence was low without any severe cases. In conclusion, risedronate 75 mg once-monthly (a dosage which is 30 times higher than risedronate 2.5 mg once-daily) had non-inferior efficacy in terms of BMD and was similarly well tolerated compared to the once-daily regimen in Japanese patients with involutional osteoporosis. Consistent with the once-daily and once-weekly dosage, the once-monthly dosage of risedronate 75 mg was half that used outside Japan (150 mg). (C), 2013 The Authors. Published by Elsevier Inc. All rights reserved.