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 (28,340 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. JAMA. 2000;283:3205-3210