Clinical efficacy on fracture risk and safety of 0.5 mg or 1 mg/month intravenous ibandronate versus 2.5 mg/day oral risedronate in patients with primary osteoporosis

Abstract

This randomized, double-blind study assessed the antifracture efficacy and safety of intermittent intravenous (IV) ibandronate versus oral daily risedronate in Japanese patients with primary osteoporosis. Ambulatory patients aged ≥60 years were randomized to receive 0.5 or 1 mg/month IV ibandronate plus oral daily placebo or 2.5 mg/day oral risedronate, the licensed dose in Japan, plus IV placebo. The primary end point was noninferiority of ibandronate versus risedronate for first new or worsening vertebral fracture over 3 years. A total of 1,265 patients were randomized. A total of 1,134 patients formed the per-protocol set. Both ibandronate doses were noninferior to risedronate: 0.5 mg, hazard ratio (HR) 1.09 [95 % confidence interval (CI) 0.77-1.54]; 1 mg, HR 0.88 (95 % CI 0.61-1.27). The rate of first new vertebral fracture over 3 years was 16.8 % (95 % CI 12.8-20.8) for 0.5 mg ibandronate, 11.6 % (95 % CI 8.2-15.0) for 1 mg ibandronate, and 13.2 % (95 % CI 9.6-16.9) for risedronate. Significant increases in bone mineral density relative to baseline were observed with all treatments after 6 months, with substantial reductions in bone turnover markers after 3 months. Greatest efficacy was obtained with 1 mg ibandronate. Analyses in women only showed similar results to the overall population. No new safety concerns were identified. This study demonstrated the noninferiority of IV ibandronate to the licensed Japanese dose of oral risedronate and suggested that 1 mg/month is an effective dose in Japanese patients with primary osteoporosis.

Fig. 1

Patient flow through the study (men and women)

Fig. 2

Vertebral fracture efficacy: forest plot of hazard ratios for the first new or worsening vertebral fracture in a all patients and b women only. c Life table analysis for the first new vertebral fractures during the study. CI confidence interval

Fig. 3

Incidences of osteoporotic nonvertebral fractures, major six nonvertebral fractures, first clinical vertebral fractures, and total clinical fractures through 3 years. P value (log rank) for ibandronate versus risedronate: *P = 0.652 (0.5 mg), P = 0.605 (1 mg) ^† P = 0.752 (0.5 mg), P = 0.449 (1 mg) ^‡ P = 0.468 (0.5 mg), P = 0.568 (1 mg) ^§ P = 0.497 (0.5 mg), P = 0.298 (1 mg)

Fig. 4

Mean relative change from baseline (with 95 % CI) throughout 3 years in a BMD at the lumbar spine (L2–L4); b BMD at the total hip; c uCTX; d serum BALP. P value (t test) for 1 mg ibandronate versus risedronate: L2–L4: P = 0.001 (6 months), P = 0.001 (24 months), P = 0.005 (36 months), total hip: P = 0.001 (24 months), P < 0.001 (36 months), *P < 0.005 for 1 mg ibandronate versus 0.5 mg ibandronate. CI confidence interval, L lumbar, BMD bone mineral density, uCTX creatinine-corrected urinary collagen type 1 cross-linked C-telopeptide, BALP bone-specific alkaline phosphatase

Fig. 5

Change in the incidence of acute phase reactions between first and subsequent dose of study medication