This review assessed whether statin use was associated with a reduced risk for fracture. Although the review had several methodological limitations and the pooling of the results was inappropriate, the authors' recommendation for further controlled trials into the effect of statins on fracture appears justified.

To determine whether statin use was associated with a reduced risk for fracture. This paper was based on an analysis of four prospective studies and a meta-analysis, but this abstract focuses on the meta-analysis.

MEDLINE was searched up to January 2002 to locate studies reported in English. Abstracts from major scientific meetings were located and experts were contacted for unpublished studies.

Study designs of evaluations included in the review

No specific study designs were stipulated. The review included both observational studies and clinical trials.

Specific interventions included in the review

To be eligible for inclusion in the review, studies needed to assess statin use at baseline.

Participants included in the review

The only inclusion criterion for participants in the review appeared to be women or men using statins. The inclusion criteria for individual studies were varied: men and women or women only with varying age limits, women with low bone mass, and men and/or women suffering from heart disease.

Outcomes assessed in the review

To be eligible for inclusion in the review, studies needed to document hip or any nonspine fracture outcomes.

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

The authors did not state that they assessed validity.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. Reported relative hazards or odds ratios (ORs) and 95% confidence intervals (CIs) were extracted from the studies using the most adjusted risk estimate available.

How were the studies combined?

A random-effects model was used to combine the studies.

How were differences between studies investigated?

Statistical heterogeneity was explored using the chi-squared test. For studies with multiple results, the effect of the differing results on the summary estimate was tested. Analyses were conducted to investigate the effects of gender, multivariate adjustment and different study designs.

Two clinical trials (n=13,458) and eight observational studies (number of participants unclear) were included.

Hip fracture (8 observational studies and 2 clinical trials).

The observational studies (9,946 statin users, 141,554 statin nonusers) showed a reduced risk of hip fracture for statin users (OR 0.43, 95% CI: 0.25, 0.75). Statistical heterogeneity was observed but was no longer present when one study (Women's Health Initiative study) was removed from the analysis. The removal of this study did not substantially affect the results of the meta-analysis.

The clinical trials (total number 13,458, number of statin users unstated) did not find a statistically significant reduction in risk (OR 0.87, 95% CI: 0.48, 1.58). Heterogeneity was not observed for these trials.

Nonspine fracture.

A similar contradiction in findings was observed for nonspine fracture. Based on six observational studies (2,893 statin users, 54,728 statin nonusers) the OR was 0.69 (95% CI: 0.55, 0.88); there was no evidence of statistical heterogeneity. Two clinical trials (total number 13,458, number of statin users unstated) gave an OR of 1.02 (95% CI: 0.83, 1.26). Again, heterogeneity was not observed for these trials.

Given the positive results found in the observational studies, controlled trials specifically designed to test the effect of statins for the prevention of fracture are needed.

The review question was defined and the inclusion criteria were broadly specified. Searching was limited to one database although supplementary methods were employed, thus reducing the risk of missing studies. The review was limited to studies reported in English, introducing the possibility of language bias. The quality of the studies was not assessed. The methods of conducting the review were not described in full, so it was not possible to assess the possibility of bias in these procedures. The pooling of the results did not appear to be appropriate as different measures of risk estimate were used in the included studies. The authors provided a number of explanations for the differing results between the observational studies and the controlled trials, and their conclusion that further trials should be conducted appears appropriate.

Practice: The authors did not state any implications for practice.

Research: The authors stated that adequately powered trials including high-risk individuals, specifically designed to test the effect of statins on skeletal metabolism and fracture, are needed.

Public Health Service, grant numbers 1-R01-AG05407, 1-R01-AR35582, 5-R01-AG05394, 1-R01-AR35584, 1-R01-AR35583.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.