Use of statins and risk of fractures. (Abstracts of Current Literature).

van Staa TP, Wegman S, de Vries F, et al (Department of Pharmacoepidemiology and Pharmacotherapy, University of Utrecht, Utrecht, the Netherlands; Procter and Gamble Pharmaceuticals, Staines, England; Medical Research Council Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, England), JAMA. 2001;285:1850-1855.

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are medications used to treat hypercholesterolemia. In theory, statin use may affect osteoclast-mediated bone resorption and, therefore, reduce the risk of fracture. The purpose of this study was to determine if statin use was associated with decreased fracture risk.

The authors completed a population-based case-control study from the United Kingdom. The information was gathered from the General Practice Research Database (GPRD), which contains the computerized medical records from 683 general practices. The authors noted that previous studies have shown that the GPRD had a high level of completeness and validity and was a suitable instrument for this study.

The study population consisted of patients who were 50 years old or older and who had a fracture of the vertebrae, clavicle, humerus, radius or ulna, carpus, hip, ankle, or foot. The patients in the control group were similar adults without a history of any type of fracture who were matched to the case patients by age (within 1 year), sex, and the type of medical practice responsible for their care.

The authors also determined the subjects' exposure to statins and nonstatin lipid-lowering drugs (eg, bezafibrate, ciprofibrate, clofibrate). Current statin users were defined as patients who received a prescription for "statin" within the past 6 months. Past statin users were defined as patients who received one or more statin prescriptions but had stopped treatment for more than 6 months. Exposure to nonstatin lipid-lowering drugs was determined and defined in the same manner.

Conditional logistic regression was used to determine the adjusted odds ratios (OR) of fractures in statin users compared with nonstatin users and between statin users and patients using nonstatin lipid-lowering drugs. The analysis was controlled by including clinical variables that may have been associated with fracture risk, such as diabetes mellitus, rheumatoid arthritis, hyperthyroidism, congestive heart failure, seizures, anemia, dementia, depression, psychotic disorder, cerebrovascular accident, and chronic obstructive pulmonary disease. The analysis also accounted for prescriptions for anticonvulsants, nonsteroidal anti-inflammatory drugs, methotrexate, hormone replacement therapy, thiazide diuretics, anxiolytics and hypnotics, antipsychotics, antidepressants, anti-Parkinson drugs, corticosteroids, and bronchodilators. Finally, smoking status and body mass index (BMI) were other risk factors that were identified as potentially contributing to the incidence of fracture.

The study population consisted of 81,880 patients who had a fracture and a matched control group of 81,880 subjects. The study population had a mean age of 70 years, and women comprised 75.6% of this group. Odds ratios were estimated and adjusted for smoking, medication, BMI, and illnesses associated with fracture risk. After analysis, the factors found to be strongly associated with fracture risk were systemic corticosteroid use (OR=1.36; 95% confidence interval [CI]=1.29, 1.43) and hormone replacement therapy use (OR=0.75; 95% CI=0.71, 0.79). No significant relationship was found between statin use or nonuse and fractures. The adjusted OR for fractures in current statin users compared with nonusers was 1.01 (95% CI=0.88, 1.16). A relationship did not exist between long-term statin use (OR=1.17, 95% CI=0.99, 1.40) or short-term statin use (OR=0.71, 95% CI=0.50, 1.01) and the incidence of fractures between these groups and the control group subjects. The adjusted OR for fractures was 1.02 (95% CI=0.83, 1.24) for statin users compared with users of other nonstatin lipid-lowering drugs. In addition, 62% of statin users had a BMI of 25 kg/[m.sup.2] or greater Compared with 52.2% of the control nonstatin users.

The authors concluded that this study does not support the hypothesis that statins protect against age-related fracture. There was a lower risk of hip fractures among statin users in this study. Based on the BMI information, however, the authors concluded that this finding was due to the confounding obesity effect, which has been associated with a reduction in hip fracture risk (ie, increased bone density and fat's shock-absorbing capacity). The use of statins, at clinically prescribed dosages, was not associated with a decreased fracture risk among patients in this population-based study.

Ricardo Fernandez, PT, OCS
HealthSouth Sports Medicine
and Rehabilitation
Palos Heights, Ill