HMG-CoA Reductase Inhibitors and the Risk of Vertebral Fracture

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Abstract
Statins inhibit an enzyme in the mevalonate pathway and therefore may affect bone. In this first study on both symptomatic and nonsymptomatic vertebral fractures in the elderly (N = 3469), we show that long‐term statin use is significantly associated with a 50% lower vertebral fracture risk. Randomized trials on statins and fractures, carried out in populations at risk for fractures, are needed. Introduction: Statins are cholesterol‐lowering agents that could potentially affect bone. Previous studies on statin use and fracture risk reported contradictory results and did not include both symptomatic and nonsymptomatic vertebral fractures. Materials and Methods: To examine the association between statin use, vertebral fractures, and lumbar spine BMD, we performed a prospective population‐based cohort study in men and women (N = 3469) ≥55 years of age. These individuals had both baseline and follow‐up spinal X‐rays available. Statin use was obtained from detailed computerized pharmacy data, and the total number of days of exposure before second X‐ray was calculated. A multivariate logistic regression model was fitted to calculate odds ratios and CIs. Results: During a mean follow‐up of 6.5 years, 176 incident vertebral fractures occurred. There were 508 statin users and 16 exposed cases. The adjusted relative risk for incident vertebral fracture in users of statins (compared with nonusers) was 0.58 (95% CI, 0.34‐0.99). The relative risk decreased on higher cumulative use to 0.52 (95% CI, 0.28‐0.97) for use for more than 365 days during the study period. Use of (the hydrophilic statin) pravastatin and use of nonstatin cholesterol‐lowering drugs was not significantly associated with vertebral fracture risk. Statin use was not significantly associated with lumbar spine BMD. Conclusion: Statin use is associated with a lower risk of vertebral fracture. Randomized clinical trials in a population at risk for fracture are needed to examine this association.