HMG-CoA Reductase Inhibitors and the Risk of Fractures

Abstract

The statins, which inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, lower the risk of cardiovascular events and death in hyperlipidemic individuals, and results of recent studies suggest that they also affect bone metabolism. Increased bone formation and trabecular bone volume have been described in rats, and preliminary observations in older women suggest increased bone mineral density. Investigators in this large-scale case-control study analyzed data from the United Kingdom–based General Practice Research Database, which consists of data from about 300 practices that were collected from the late 1980s to late 1998. Investigators sought to determine whether statins and other lipid-lowering drugs lower the risk of bone fracture. Cases were 3940 persons aged 50 years and older with bone fracture, and the control group consisted of 23,379 individuals matched for age, gender, and general practice attended. Current, recent, or past exposure to statins (regardless of the total number of prescriptions) correlated with a significantly reduced risk of bone fracture compared with those not using any lipid-lowering drugs. The respective odds ratios were 0.55, 0.67, and 0.87. These results were obtained after controlling for smoking, body mass index, number of physician visits, and use of steroids and estrogen. The effect of statin on fracture risk was not substantially influenced by the site of injury, age, or gender. In contrast to statin therapy, the current use of fibrates or other lipid-lowering drugs did not relate to a significantly reduced risk of fracture. The adjusted odds ratio for fibrates was 0.87, and for other lipid-lowering agents, 0.76. This large-scale case-control analysis indicates that exposure to statins correlates with a substantially reduced risk of developing bone fractures. The association is most evident in those currently taking statins but is confirmed even after as few as one to four prescriptions, representing a treatment time of about 1 to 4 months. The effect is observed in those older than 50 years of age and applies to multiple skeletal sites. JAMA 2000;283:3205–3210