Hydroxymethylglutaryl-coenzyme A reductase inhibitors and osteoporosis: a meta-analysis

Studies determining the association between hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) and bone metabolism are mixed. We conducted a systematic review to assess the potential impact of statins on fractures, bone mineral density and bone markers. We searched Medline, Embase, the Cochrane Library, and Federal Research in Progress (FEDRIP). Inclusion criteria consisted of human studies with measurable outcomes, which were rated as good or fair according to the United States Preventive Services Task Force (USPSTF) criteria. The effects of statins on bone mineral density (BMD), bone markers and fracture risk were independently extracted by two reviewers and were combined by use of a random-effects model. The 31 analyzed studies included 24 observational studies and seven randomized controlled trials. Overall, statin use was associated with fewer hip fractures (OR 0.60, 95% CI 0.45-0.78) and improved hip BMD (Z score 0.12, 95% CI 0.05-0.19), with a non-significant reduction in vertebral fractures and no effect on vertebral BMD. In subgroup analysis of studies that involved only women there was a reduction in hip fractures (OR 0.75, 95% CI 0.60-0.95) and improvement in hip BMD (Z score 0.11, 95% CI 0.04-0.18). Vertebral BMD was unchanged, and only one study reported on vertebral fractures, finding improvement. Statins had only small effects on bone markers, with a decrease in alkaline phosphatase [standardized mean difference (SMD) -0.18, 95% CI -0.34 to -0.01], an increase in NTX (SMD 0.39, 95% CI 0.07-0.71), with no effect on osteocalcin or CTX. The statistically significant improvement in hip fracture risk was seen only in case-control trials, not in either the eight prospective trials or the two randomized controlled trials (RCTs). Statins may have a beneficial impact on bone metabolism and fracture risk; randomized controlled trials are needed to explore this association.