Statins Decrease the Risk of Fractures Among Older Women
ABSTRACTS & Commentary
Three reports have documented the effect of statins on the risk of fracture in older women. Chan and associates reported the results of a case-control study using data from six health maintenance organizations. The study included the five products marketed in the United States before September 1997. Statin users, compared with women who had no record of statin use, had a 52% reduced risk of non-pathological fracture (odds ratio [OR] 0.48; confidence interval [CI] 0.27-0.83). Statistical significance was achieved only when there was a prescription record of 13 or more statin prescriptions during the two years prior to the fracture, or the date of the study. Meier and colleagues reported a case-control analysis of the United Kingdom General Practice Research Data Base. The current use of statins was associated with a 45% reduced risk of fracture (OR 0.55; CI 0.44-0.69). Wang and colleagues reported a case-control study based in New Jersey using Medicare, Medicaid, Pharmacy Assistance for the Aged, and Disability Program data. Again, current use of statins was associated with a 50% reduced risk of fracture (OR 0.550; CI 0.33-0.476). (Chan KA, et al. Lancet 2000;355:2185-2188; Meier CR, et al. JAMA 2000;283:3205-3210; Wang PS, et al. JAMA 2000;283:321-3216).
Comment by Leon Speroff, MD
These three case-control studies examined the use of statins as a group in bone fracture risk. Statins are 3-hydroxyrHMG-CoA reductase inhibitors well demonstrated to reduce the risk of cardiovascular morbidity and mortality. The rationale for performing these studies can be traced to animal studies, indicating that statins increase bone formation and bone density. These studies indicate that the current use of statins is associated with a reduced fracture risk, an effect that could not be found with other lipid-lowering drugs.
The editorial accompanying the JAMA articles1 emphasizes that these observational studies do not provide sufficient certainty that clinicians should begin to prescribe statins to reduce fracture risk. This is especially true because we have other agents available for use supported by clinical trial data. Indeed, a future clinical trial should compare the effect of statin use to other agents. Thus, cardiovascular indications remain the primary use of statins.
The mechanism of action by which statins might prevent bone loss is unknown. However, bisphosphonates and statins inhibit different steps in the pathway that leads from cholesterol to acetyl CoA. In the case of bisphosphonates, this inhibition leads to inhibition of osteoclastic activity and apoptosis of osteoclasts. Perhaps statins have the same effect. On the other hand, in animal studies, statins increase bone formation, an effect not seen with bisphosphonates. Thus, the mechanism of action for these two agents may not be identical.
Another benefit of statin use, newly recognized, is the demonstration in the HERS trial that statin use was associated with a 50% reduced risk of venous thrombosis (relative risk 0.5; CI 0.2-0.9).2 Cardiovascular benefits associated with the statin family of drugs are well demonstrated, and the safety record is excellent. At this point in time, however, it would not be appropriate to recommend statin use for the prevention of osteoporosis. Dose response studies have not been accomplished for this purpose; the effect has not been proven by clinical trials; and other proven agents are available. These studies should be viewed as added benefits associated with an excellent drug intended to lower cardiovascular morbidity and mortality.
References
1. Cummings SR, Bauer DC. JAMA 2000;283:3255-3257.
2. Grady D, et al. Ann Intern Med 2000;132:689-696.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content