BACKGROUND: Animal studies have demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) increase bone formation and bone volume. Although studies in humans suggest that statins may increase bone formation, no research has been done to determine whether older persons taking these drugs will have a decreased risk of fracture.
POPULATION STUDIED: The study used data from the United Kingdom-based General Practice Research Database, which includes information from approximately 300 general practices. The base population consisted of more than 91,000 individuals aged 50 to 89 years. Of these, more than 28,000 had received at least 1 prescription for a lipid-lowering drug for hyperlipidemia, approximately 13,000 had hyperlipidemia but were not taking lipid-lowering agents, and 50,000 were randomly selected patients without a diagnosis of hyperlipidemia. Patients were excluded if they had a diagnosis of osteoporosis, osteomalacia, malignancy, alcoholism, or if they were taking bisphosphonates. A total of 3940 patients who had a bone fracture were identified by the International Classification of Diseases-eighth revision (ICD-8) and were verified by hospital discharge records or referral letters to specialists. These case patients were matched for age, sex, practice attended, calendar year, and years enrolled to 23,379 control group patients from the base population who had not had a fracture.
STUDY DESIGN AND VALIDITY: This was a large population-based case-control study nested within an ongoing study. Members of the 3 groups were followed until they developed a fracture, left the practice, or died. Patients taking a lipid-lowering drug were categorized as being current users, recent users, and past users.
OUTCOMES MEASURED: The primary outcome was the risk of development of a first-time fracture of the femur, humerus, hand, wrist, lower arm, clavicle, vertebral body, foot, or other unspecified fracture among the 3 groups as estimated by the odds ratio. The authors used statistical analysis (logistic regression) to consider the type, timing, and duration of treatment as estimated by numbers of prescriptions filled.
RESULTS: After adjusting for variables including smoking status, weight, hormone replacement therapy or corticosteroid use, and the number of office visits before the fracture, patients who had any current or recent recorded prescriptions for statins before the date of fracture had a significantly lowered risk of fracture with adjusted odds ratios of 0.55 for current users (95% confidence interval [CI], 0.44-0.69) and 0.67 (95% CI, 0.50-0.92) for recent users of statins. The odds ratio for previous users of statins was not statistically significant. A consistent class effect was noted, with all statins associated with decreased fracture risk. Other lipid-lowering agents were not associated with a reduced risk for fracture. The effect of statins on risk of fracture did not differ by the skeletal site of fracture, age group, or sex.
This population-based case-control study suggests that the HMG-CoA reductase inhibitors, but not other lipid-lowering agents, are associated with a significantly decreased risk of subsequent fracture in humans, especially in current users. There may be biologic plausibility for this effect in that both statins and bisphosphonates act in the same metabolic pathway (the mevalonate pathway) that may ultimately affect osteoclastic activity. Other recently reported case-controlled studies find protective effects of similar magnitude. Statin use has been associated with a 43% to 50% lowering of risk of hip fracture among elderly users, and another study reports a reduction of risk of fracture of 52% among elderly women using statins. 1,2
However, these studies cannot establish a causal relationship between statin use and decreased risk of fracture. As with all observational studies, it is possible that unknown factors may provide alternative explanations for these findings. Large randomized controlled trials are needed to confirm any benefit of statins in reducing risk of fracture. In addition, the added benefit of statins to current regimens for fracture prevention (calcium, Vitamin D, estrogen, biphosphonat