HMG-CoA reductase inhibitors and the risk of fractures

Context Recent animal studies have suggested that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) increase bone formation, volume, and density. It is unknown whether use of statins is associated with a decreased risk of fractures in humans. Objective To determine whether exposure to statins, fibrates, or other lipid-lowering drugs is associated with reduced bone fracture risk. Design Population-based, nested case-control analysis. Setting The UK-based General Practice Research Database (GPRD), comprising some 300 practices, with data collection from the late 1980s until September 1998. Subjects Within a base population of 91 611 individuals aged at least 50 years (28340 individuals taking lipid-lowering drugs, 13 271 untreated individuals with a diagnosis of hyperlipidemia, and 50 000 randomly selected individuals without diagnosis of hyperlipidemia), we identified 3940 case patients who had a bone fracture and 23 379 control patients matched for age (+/-5 years), sex, general practice attended, calendar year, and years since enrollment in the GPRD, Main Outcome Measures Use of statins, fibrates, or other lipid-lowering drugs in case patients vs control patients. Results After controlling for body mass index, smoking, number of physician visits, and corticosteroid and estrogen use, current use of statins was associated with a significantly reduced fracture risk (adjusted odds ratio [OR], 0.55; 95% confidence interval [CI], 0.44-0.69) compared with nonuse of lipid-lowering drugs. Current use of fibrates or other lipid-lowering drugs was not related to a significantly decreased bone fracture risk (adjusted OR, 0.87; 95% CI, 0.70-1.08 and adjusted OR, 0.76; 95% CI, 0.41-1.39, respectively). Conclusions This study suggests that current exposure to statins is associated with a decreased risk of bone fractures in individuals age 50 years and older. This finding has a potentially important public health impact and should be confirmed further in controlled prospective trials.