Twelve studies, seven case-control and five cohort studies, were included in the review. The number of participants was at least 855,377 (ranging from 4,871 to 456,866); one cohort study did not report on numbers of participants in the study. The mean quality score was 6.91 out of a maximum score of 9; four studies were considered of low quality.
Overall analysis
There was a significant positive association between the use of SSRIs and risk of fracture (adjusted OR 1.69, 95% CI 1.51 to 1.90; 12 studies; Ι²=89.9%).
Subgroup analyses
Significant positive associations between risk of fracture and use of SSRIs were identified for all subgroup analyses, except exposure to SSRIs more than six weeks before the test date . All subgroup analyses had heterogeneity values greater than 40% except for two subgroup factors: geographic location in the USA and men. The authors reported that higher risks were found for the following subgroups: case control studies; studies undertaken in countries with high latitude; studies adjusting for fewer than four variables; studies of fracture of the hip or femur; and studies of SSRIs administered within six weeks of the test date. However, they did not report statistical tests of the difference in treatment effect.
No statistically significant effect on fracture risk was identified in meta-regression analyses for latitude, quality assessment, study design and the number of key adjusted variables for osteoporotic fracture risk factors.
There was no evidence of publication bias from inspection of funnel plots or the results of the Egger test (P=0.051).