Effects of Statins on Relative Risk of Fractures for Older Adults: An Updated Systematic Review With Meta-Analysis

J Am Med Dir Assoc. 2019 Dec;20(12):1566-1578.e3. doi: 10.1016/j.jamda.2019.06.027. Epub 2019 Aug 5.

Abstract

Objectives: Basic and translational studies have found statin treatment may have beneficial effects on bone metabolism; however, whether statins reduce the risk of fractures in older adults is still in debate. Therefore, we aimed to summarize the up-to-date evidence on risk of fracture among older individuals with statin use.

Design: Systematic literature review and meta-analysis.

Setting and participants: Twenty-one observational studies and 2 randomized controlled trials (RCTs) comprising 1,783,123 participants aged at least 50 years were retrieved from PubMed, Embase, and the Cochrane Library.

Measures: We estimated summary relative risks (RRs) with 95% confidence intervals (CIs) using the random-effects model. Subgroup analysis was performed to explore the potential source of heterogeneity.

Results: Meta-analysis of observational studies suggested that statin treatment was significantly associated with reduced risk of all fractures (RR 0.80, 95% CI 0.72-0.88), among which hip fracture (RR 0.73, 95% CI 0.64-0.82) and lower extremity fracture (RR 0.69, 95% CI 0.54-0.88) showed consistent results, whereas no significant decreased risk was observed with respect to other fracture sites. Subgroup analyses showed that among the statin users, fracture risk was reduced in both genders, older adults ≥50 years old, those with short drug duration (< year) or medium to high statin dose (>90 defined daily dose), those taking atorvastatin, and in Europeans and Americans. Meta-analysis of RCTs revealed no significant effect of statin treatment on the risk of fractures (RR 1.00, 95% CI 0.87-1.15).

Conclusions and implications: Overall, the findings of this updated meta-analysis indicated no solid evidence supporting that statins have a beneficial effect associated with reduced risk of fractures for older adults. Our findings should be further confirmed in future larger population-based prospective cohort studies or well-designed RCTs.

Keywords: HMG-CoA reductase inhibitor; fractures; meta-analysis; pharmacoepidemiology; statins.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Fractures, Bone / prevention & control*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Risk*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors