Statin Use, Clinical Fracture, and Bone Density in Postmenopausal Women: Results from the Women's Health Initiative Observational Study
- Andrea Z. LaCroix, PhD;
- Jane A. Cauley, DrPH;
- Mary Pettinger, MS;
- Judith Hsia, MD;
- Douglas C. Bauer, MD;
- Joan McGowan, PhD;
- Zhao Chen, PhD;
- Cora E. Lewis, MD;
- S. Gene McNeeley, MD;
- Maureen D. Passaro, MD; and
- Rebecca D. Jackson, MD
- From Women's Health Initiative Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Pittsburgh, Pittsburgh, Pennsylvania; George Washington University and Medlantic Research Institute, Washington, DC; University of California, San Francisco, San Francisco, California; National Institute of Arthritis and Musculoskeletal Diseases, National Institutes of Health, Bethesda, Maryland; University of Arizona, Tucson, Arizona; University of Alabama at Birmingham, Birmingham, Alabama; Wayne State University, Detroit, Michigan; and Ohio State University, Columbus, Ohio.
Abstract
Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to stimulate bone formation in laboratory studies, both in vitro and in vivo. While early epidemiologic studies showed lower risk for hip fracture among statin users than nonusers, subsequent studies have produced mixed results.
Objective: To examine the association of statin use with incidence of hip, lower arm or wrist, and other clinical fractures and with baseline levels of bone density.
Design: Prospective study.
Setting: Women's Health Initiative Observational Study conducted in 40 clinical centers in the United States.
Participants: 93 716 postmenopausal women ages 50 to 79 years.
Measurements: Rates of hip, lower arm or wrist, and other clinical fractures were compared among 7846 statin users and 85 870 nonusers over a median follow-up of 3.9 years. In 6442 women enrolled at three clinical centers, baseline levels of total hip, posterior–anterior spine, and total-body bone density measured by using dual-energy x-ray absorptiometry were compared according to statin use.
Results: Age-adjusted rates of hip, lower arm or wrist, and other clinical fractures were similar between statin users and nonusers regardless of duration of statin use. The multivariate-adjusted hazard ratios for current statin use were 1.22 (95% CI, 0.83 to 1.81) for hip fracture, 1.04 (CI, 0.85 to 1.27) for lower arm or wrist fracture, and 1.11 (CI, 1.00 to 1.22) for other clinical fracture. Bone density levels did not statistically differ between statin users and nonusers at any skeletal site after adjustment for age, ethnicity, body mass index, and other factors.
Conclusion: Statin use did not improve fracture risk or bone density in the Women's Health Initiative Observational Study. The cumulative evidence does not warrant use of statins to prevent or treat osteoporosis.
Article and Author Information
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Grant Support: By the National Institutes of Health contracts for the Women's Health Initiative Clinical Centers and Clinical Coordinating Center.
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Potential Financial Conflicts of Interest:Consultancies: A.Z. LaCroix (Pfizer); J. Hsia (Merck); D.C. Bauer (AstraZeneca, Pfizer); R.D. Jackson (Proctor & Gamble, Merck); Honoraria: J.A. Cauley (Eli Lilly, Proctor & Gamble); J. Hsia (Pfizer); R.D. Jackson (Proctor & Gamble, Merck); Stock ownership or options (other than mutual funds): R.D. Jackson (Proctor & Gamble); Grants received: A.Z. LaCroix (Merck, Pfizer); J.A. Cauley (Merck, Eli Lilly, Pfizer); J. Hsia (Merck, Pfizer); D.C. Bauer (Merck, Proctor & Gamble); C.E. Lewis (Eli Lilly, Pfizer); R.D. Jackson (Proctor & Gamble, Merck); Grants pending: J.A. Cauley (Novartis); C.E. Lewis (Novartis).
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Requests for Single Reprints: Andrea Z. LaCroix, PhD, Women's Health Initiative Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, MP-1002, PO Box 19024, Seattle, WA 98109-1024.
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Current Author Addresses: Dr. LaCroix and Ms. Pettinger: Women's Health Initiative Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, MP-1002, PO Box 19024, Seattle, WA 98109.
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Dr. Cauley: Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, 130 DeSoto Street, Room A524, Pittsburgh, PA 15261.
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Dr. Hsia: George Washington University, 2150 Pennsylvania Avenue NW, Washington, DC 20037.
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Dr. Bauer: University of California, San Francisco, 74 New Montgomery, Suite 600, San Francisco, CA 94105.
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Dr. Chen: University of Arizona, 2501 East Lee Street, Tucson, AZ 85716.
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Dr. Lewis: University of Alabama at Birmingham, 1717 11th Avenue South, Room 614, Birmingham, AL 35205.
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Dr. McNeeley: Wayne State University, 4707 St. Antoine, Detroit, MI 48201.
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Dr. Passaro: Medstar Research Institute, 650 Pennsylvania Avenue SE, Suite 50, Washington, DC 20003.
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Dr. Jackson: The Ohio State University, 198 McCampbell, 1581 Dodd Drive, Columbus, OH 43210.
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Author Contributions: Conception and design: A.Z. LaCroix, J.A. Cauley, J. McGowan, C.E. Lewis, R.D. Jackson.
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Analysis and interpretation of the data: A.Z. LaCroix, J.A. Cauley, M. Pettinger, J. Hsia, D.C. Bauer, J. McGowan, Z. Chen, R.D. Jackson, S.G. McNeeley.
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Drafting of the article: A.Z. LaCroix.
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Critical revision of the article for important intellectual content: A.Z. LaCroix, J.A. Cauley, J. Hsia, D.C. Bauer, Z. Chen, C.E. Lewis, M.D. Passaro, R.D. Jackson, S.G. McNeeley.
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Final approval of the article: A.Z. LaCroix, J.A. Cauley, M. Pettinger, J. Hsia, D.C. Bauer, J. McGowan, Z. Chen, C.E. Lewis, M.D. Passaro, R.D. Jackson, S.G. McNeeley.
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Provision of study materials or patients: J. Hsia, C.E. Lewis, M.D. Passaro.
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Statistical expertise: A.Z. LaCroix, M. Pettinger.
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Obtaining of funding: C.E. Lewis.
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Administrative, technical, or logistic support: A.Z. LaCroix, C.E. Lewis.
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Collection and assembly of data: A.Z. LaCroix, J.A. Cauley, J. Hsia, C.E. Lewis, R.D. Jackson.
- Copyright ©2004 by the American College of Physicians
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