Statins and fracture risk. A systematic review

PURPOSE: To summarize current evidence on statin use and fracture risk and to explore potential sources of heterogeneity among study results. METHODS: A computerized search was conducted on MEDLINE, EMBASE, and the Cochrane databases using the keywords HMG-CoA reductase inhibitor, osteoporosis, and fractures. A meta-analysis was performed to summarize results of studies identified. RESULTS: Statin use was associated with a 23% lower fracture risk (OR = 0.77, 95%CI: 0.66-0.90). An effect of statins was found in case-control (OR = 0.62, 0.45-0.85, n = 6) and cohort (OR = 0.77, 0.59-1.00, n = 8) studies, but not in post hoc analyses of randomized trials (OR = 1.03, 0.91-1.16, n = 4). A reduced risk with statin use was found for fractures of the hip (OR = 0.58, 0.46-0.74, n = 16), spine (OR = 0.65, 0.48-0.88, n = 8) and other sites (OR = 0.77, 0.60-1.00, n = 7), and both in women (OR = 0.80, 0.66-0.96, n = 11) and men (OR = 0.62, 0.36-1.08, n = 3). Among the observational studies that also evaluated the effect of other lipid-lowering drugs, no reduced fracture risk was found for these agents (OR = 0.96, 0.85-1.09, n = 10). The test for heterogeneity was significant for study results of statin use versus no-use (p < 0.01). Meta-regression analyses suggested that study design might partly account for the heterogeneity. There was an indication of publication bias by examining Begg's plot, although Egger's test was not significant (p = 0.13). CONCLUSIONS: Current evidence does not support an effect of statins in preventing fractures given (i) the lack of association in randomized trials, (ii) the heterogeneity among observational studies, (iii) the potential residual confounding, and (iv) the potential publication bias.