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Effects of Atorvastatin on Bone in Postmenopausal Women with Dyslipidemia: A Double-Blind, Placebo-Controlled, Dose-Ranging Trial

Michigan Bone and Mineral Clinic (H.G.B.), Detroit, Michigan 48236; Beth Israel Deaconess Medical Center and Harvard Medical School (D.P.K.), Boston, Massachusetts 02215; Regional Bone Center (R.S.L.), Helen Hayes Hospital, West Haverstraw, New York 10993; New Mexico Clinical Research and Osteoporosis Center (E.M.L.), Albuquerque, New Mexico 87106; Bethesda Health Research (M.A.B.), Bethesda, Maryland 20892; Pacific Biometrics, Inc. (E.T.L.), Seattle, Washington 98119; Asia Biometrics Centre (W.L.), Pfizer Global Pharmaceuticals, Pfizer Australia, West Ryde, New South Wales 2114, Australia; and Oregon Osteoporosis Center (M.R.M.), Portland, Oregon 97213

Address all correspondence and requests for reprints to: Henry G. Bone, M.D., Director, Michigan Bone and Mineral Clinic, 22201 Moross Road, Suite 260, Detroit, Michigan 48236-2175. E-mail: hgbone.md{at}att.net.

Context: In preclinical models, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A 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: Our objective was to determine whether clinically significant skeletal benefits result from hydroxymethylglutaryl-coenzyme A reductase inhibition in postmenopausal women.

Design and Setting: We conducted a prospective, randomized, double-blind, placebo-controlled, dose-ranging comparative clinical trial at 62 sites in the United States.

Participants: Participants included 626 postmenopausal women with low-density lipoprotein cholesterol levels of at least 130 mg/dl (3.4 mmol/liter) and less than 190 mg/dl (4.9 mmol/liter), 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 was administered.

Main Outcome Measures: We assessed percent change from baseline in lumbar (L1–L4) spine bone mineral density with each dose of atorvastatin compared with placebo.

Results: At 52 wk, 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.