Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Risedronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts.

OBJECTIVES: To assess the efficacy of residronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

SEARCH STRATEGY: We searched CENTRAL, MEDLINE and EMBASE. Relevant randomized controlled trials published between 1966 to 2007 were identified.

SELECTION CRITERIA: Women receiving at least one year of risedronate for postmenopausal osteoporosis were compared to those receiving placebo or concurrent calcium/vitamin D or both. The outcome was fracture incidence.

DATA COLLECTION AND ANALYSIS: We carried out study selection and data abstraction in duplicate. Study quality was assessed through the reporting of allocation concealment, blinding and withdrawals. Meta-analysis was preformed using relative risks and a >15% relative change was considered clinically important.

MAIN RESULTS: Seven trials were included in the review representing 14,049 women. Relative (RRR) and absolute (ARR) risk reductions for the 5 mg dose were as follows. Risk estimates for primary prevention were available only for vertebral and non vertebral fractures and showed no statistically significant effect of risedronate on fractures. For secondary prevention, a significant 39% RRR in vertebral fractures (RR 0.61, 95% CI 0.50 to 0.76) with 5% ARR was found. For non-vertebral fractures, a significant 20% RRR (RR 0.80, 95% CI 0.72 to 0.90) with 2% ARR and for hip fractures there was a significant 26% RRR (RR: 0.74, 95% CI 0.59 to 0.94) with a 1% ARR. When primary and secondary prevention studies were combined, the reduction in fractures remained statistically significant for both vertebral (RR 0.63, 0.51 to 0.77) and non vertebral fractures (RR 0.80, 0.72 to 0.90)For adverse events, no statistically significant differences were found in any of the included studies. However, observational data has led to concerns regarding the potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw.

AUTHORS' CONCLUSIONS: At 5 mg/day a statistically significant and clinically important benefit in the secondary prevention of vertebral, non-vertebral and hip fractures was observed, but not for wrist. The level of evidence for secondary prevention is Gold (www.cochranemsk.org) for vertebral and non-vertebral and Silver for hip and wrist. There were no statistically significant reductions in the primary prevention of vertebral and non-vertebral fractures. The level of evidence is Silver.