The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are known to reduce cardiovascular morbidity and mortality risk in patients with hyperlipidemia. In animal studies, they have also been found to increase bone formation. Recent studies in humans suggest that statins may play a role in decreasing the risk of hip fractures. Meier and colleagues conducted this case-control study to determine whether statins, fibrates or other lipid-lowering drugs reduce the risk of fracture.
A large case-control, population-based analysis was conducted, drawing data from the General Practice Research Database in the United Kingdom for approximately a 10-year period. Data on more than 3 million patients were included. From this database, three study groups (all persons between the ages of 50 and 89 years) were identified. Group 1 comprised all patients who received statins, a fibrate or a lipid-lowering drug other than a statin or a fibrate; group 2 included patients with a diagnosis of hyperlipidemia who did not receive lipid-lowering treatment; and group 3 included patients who did not receive lipid-lowering treatment or have a diagnosis of hyperlipidemia. Follow-up was conducted until the patient had a fracture, died or was lost to follow-up. Patients were excluded if they had a diagnosis of osteoporosis, osteopenia, cancer or alcoholism, or were taking bisphosphonates.
A base population of 91,611 patients was included in the analysis: 28,340 patients were in group 1; group 2 comprised 13,271 patients; and group 3 included 50,000 randomly selected patients. During the follow-up period, 3,940 patients developed a bone fracture. In the first group, 705 bone fractures occurred (2.5 percent) compared with 681 bone fractures (5.1 percent) in group 2 and 2,554 bone fractures (5.1 percent) in group 3. Each patient with a bone fracture was matched to approximately six control patients (3,940 case patients matched with 23,379 control patients = 5.93 controls per case). In group 2 (patients with nonpharmacologically treated hyperlipidemia), the cases and controls had nearly identical risks of fractures. Conversely, the odds ratios for those who took a statin ranged from 0.51 to 0.62, depending on the length of time the statin had been taken. Adjusted odds ratios for current, recent or past exposure to statins was 0.55, 0.67 and 0.87, respectively; to fibrates 0.87, 1.05 and 0.85, respectively; and to other lipid-lowering drugs 0.76, 1.19 and 0.97, respectively.
The authors conclude that statin exposure is associated with a lower risk of bone fracture. The relationship is strongest in patients who currently take a statin, but also occurs in those who have taken statins for one to four months. Fibrates and other lipid-lowering drugs were not associated with a similar decreased risk of bone fracture (although current fibrate users, especially men, had a slightly decreased risk of vertebral fractures). Further studies are needed.