Context: In preclinical models, inhibitors of HMG-CoA reductase have been shown to positively affect bone remodeling balance. Observational studies and secondary analyses from lipid-lowering trials have yielded inconsistent results regarding the effect of these agents on bone mineral density and fracture risk.

Objective: To determine whether clinically significant skeletal benefits result from HMG-CoA reductase inhibition in postmenopausal women.

Design: Prospective, randomized, double-blind, placebo-controlled, dose-ranging comparative clinical trial.

Setting: 62 sites in the US.

Participants: 626 postmenopausal women with LDL-cholesterol levels 130 mg/dL (3.4 mmol/L) and < 190 mg/dL (4.9 mmol/L), and lumbar (L1-L4) spine bone mineral density T-score between 0.0 and -2.5.

Intervention: Once-daily placebo or 10, 20, 40, or 80 mg atorvastatin.

Main outcome measures: Percent change from baseline in lumbar (L1-L4) spine bone mineral density with each dose of atorvastatin compared with placebo.

Results: At 52 weeks, there was no significant difference between each atorvastatin and placebo group or change from baseline at any tested dose of atorvastatin or placebo in lumbar (L1-L4) spine bone mineral density. Nor did atorvastatin produce a significant change in bone mineral density at any other site. Changes in biochemical markers of bone turnover did not differ significantly between each atorvastatin and placebo group. All doses of atorvastatin were generally well tolerated, with similar incidences of adverse events across all dose groups and placebo.

Conclusions: Clinically relevant doses of atorvastatin that lower lipid levels had no effect on bone mineral density or biochemical indices of bone metabolism in this study, suggesting that such oral agents are not useful in the prevention or treatment of osteoporosis.