Two recent reports have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) might substantially reduce the risk of bone fractures in addition to reducing blood cholesterol levels and risk of cardiovascular disease (1, 2). According to the studies, statins predominantly seem to increase bone formation.
Two population-based, case-control studies were carried out to determine the risk of fractures and risk of hip fractures in elderly patients following exposure to lipid-lowering drugs. The results showed that women and men taking any kind of statins had a lower risk of fractures than those who were not. The reductions were statistically significant: 45% lower risk of all types of fractures and 88% lower risk of hip fractures were achieved in the first study and a 71% reduction in risk of hip fracture in the second. Both studies showed that use of nonstatin cholesterol-lowering drugs was not associated with a reduction in risk of fractures.
The first trial, to demonstrate whether exposure to statins, fibrates or other lipid-lowering drugs is associated with reduced bone fracture risk was carried out in a base population of 91 611 individuals aged at least 50 years (1). Nested case-control analysis identified 3 940 case patients who had a bone fracture and 23 379 controls. 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, 0.55; 95% confidence interval, 0.44-0.69) compared with non-use 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% Cl, 0.70-1.08 and adjusted OR 0.76; 95% Cl, 0.41-1.39 respectively).
The second trial, a case-controlled study to determine whether the use of statins is associated with reduced hip fracture risk in elderly patients (2), was carried out in a total of 6110 US residents aged at least 65 years. Case patients underwent surgical repair of a hip fracture in 1994. Control patients were identified at a ratio of 4:1 and frequency matched to case patients for age and sex. Use of statins in either the prior 180 days or prior 3 years was associated with a significant reduction in the risk of hip fracture, even after controlling for variables such as race, insurance status, psycho-active medications, estrogen and thiazide use, ischaemic heart disease, cancer and diabetes mellitus. Clear relationships were observed between the degree of reduction in hip fracture risk and the extent of statin use; there was no such relationships with nonstatin lipid-lowering agents. After adjusting for extent of statin use in the prior 3 years, current use was associated with a 71% reduction in risk (adjusted OR, 0.29; 95% Cl, 0.10-0.81).
However, statins that are currently approved for lowering cholesterol and reducing the risk of cardiovascular disease may not be the most effective drugs for increasing bone mass. These agents preferentially affect HMG-CoA reductase in the liver, not bone, and they have been selected and developed for their effects on circulating cholesterol concentrations. Perhaps intermittent use of high doses will stimulate bone formation more effectively than daily use of a standard dose. Research is needed to find formulations, doses, and routes of administration that optimize the effects of statins on bone without diminishing their cardiovascular benefits (3).
Because of the potential public health impact, it is important to demonstrate the effectiveness and safety of drugs that may be widely used. Even though statins seem to be quite safe (4) recommendations about prescription of statins to prevent fractures must await the results of rigorous trials to confirm the present findings. In the meantime, patients with osteoporosis should continue to be treated with agents that have been proven to reduce the risk of fractures, such as biphosphonates.
1. Meier, C.R., Schilenger, R.G., Kraennzlin, M.E. et al. HMG-CoA reductase inhibitors and the risk of fractures. Journal of the American Medical Association, 283: 3205-3210(2000).
2. Wang, P.S., Solomon, D.H., Mogan, H. et al. HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. Journal of the American Medical Association, 283: 3211-3216(2000).
3. Cummings, S.R., Bauer, D.C. Do statins prevent both cardiovascular disease and fracture? Journal of the American Medical Association, 283: 3255 (2000).
4. Rifkind, B.M. Clinical trials of reducing low-density lipoprotein concentrations. Endocrinology and Metabolism Clinics of North America, 27: 585-595 (1998).