Statins may not reduce osteoporotic fractures

Fran Lowry

February 15, 2001

Thu, 15 Feb 2001 23:30:00

London Despite several recent observational studies that suggest statins may reduce the risk of osteoporotic fractures and thus be valuable in the treatment of osteoporosis, a secondary analysis of the randomized, controlled Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial concludes there is no support for this hypothesis. The analysis, by Dr Ian R Reid (University of Auckland, New Zealand) and others for the LIPID Study Group, appears in the February 17, 2001 issue of The Lancet.

As an example of one such observational study, Reid et al cite a nested case-control study that used the large, UK General Practice Research Database to show an odds ratio for fracture of 0.55 among statin users. The authors add that similar positive findings for the statins, as confirmed by two other observational studies that made use of reimbursement databases and data from health-maintenance organizations (HMOs) in the US, , might lead practitioners to prescribe statins for their osteoporotic patients.

But, they caution: "Observational studies are always potentially subject to biases whatever measures are taken to adjust for confounding factors, so any effect of statins on bone density and fracture risk must also be assessed in randomized controlled trials."

Statins made no difference

Accordingly, they calculated the frequency of fractures from the adverse events that were reported in LIPID. The trial's primary outcome was mortality from coronary heart disease among 9014 patients randomized to placebo or pravastatin, 40 mg per day. All patients in the study had a history of myocardial infarction (MI) or hospital admission for unstable angina (UA), and initial cholesterol concentrations between 4.0 and 7.0 mmol/L.

The authors analyzed fractures in the entire study cohort, and separately for women and participants aged 65 and older, since women and the elderly have a higher risk for fracture. The analysis showed no evidence of a reduced frequency of fracture in patients treated with pravastatin. Fracture risks were similar in both treatment groups across all classifications, Reid et al note.

Use of pravastatin and hazard ratios of fracture

Number of fractures

Placebo

Pravastatin

Hazard ratio (95% CI)

P value

In entire cohort

183
175
0.94 (0.77-1.16)
0.58

In women

59
46
0.80 (0.55-1.18)
0.26

In subjects >65

81
75
0.93 (0.68-1.27)
0.65

The authors point out that the "95% CI around the relative risk of fracture show that a small effect cannot be completely ruled out, but this agent is unlikely to have clinically significant efficacy against fractures." They add that the statins come no where near the efficacy demonstrated by current treatments for osteoporosis, namely bisphosphonates and hormone replacement therapy, which lower fracture risk by "about 50%."

Because the LIPID data do not support the observed contention that statins exert positive effect on human bone, Reid et al warn against using these agents for osteoporosis. They call for further randomized controlled trials to study the effects of various statins on bone density, biochemical indices of bone cell activity, and fracture incidence "before their role in the management of skeletal disease can be adequately assessed."



Related links:

1. [Heartwire > News; Jun 27, 2000]

2. [Heartwire > News; Jun 22, 2000]


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