Background:
The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D] concentration and hip fractures is unclear.
Objective:
To see whether low serum 25(OH) vitamin D concentrations are associated with hip fractures in community-dwelling women.
Design:
Nested case–control study.
Setting:
40 clinical centers in the United States.
Participants:
400 case-patients with incident hip fracture and 400 control participants matched on the basis of age, race or ethnicity, and date of blood draw. Both groups were selected from 39 795 postmenopausal women who were not using estrogens or other bone-active therapies and who had not had a previous hip fracture.
Measurements:
Serum 25(OH) vitamin D was measured and patients were followed for a median of 7.1 years (range, 0.7 to 9.3 years) to assess fractures.
Results:
Mean serum 25(OH) vitamin D concentrations were lower in case-patients than in control participants (55.95 nmol/L [SD, 20.28] vs. 59.60 nmol/L [SD, 18.05]; P = 0.007), and lower serum 25(OH) vitamin D concentrations increased hip fracture risk (adjusted odds ratio for each 25-nmol/L decrease, 1.33 [95% CI, 1.06 to 1.68]). Women with the lowest 25(OH) vitamin D concentrations (≤47.5 nmol/L) had a higher fracture risk than did those with the highest concentrations (≥70.7 nmol/L) (adjusted odds ratio, 1.71 [CI, 1.05 to 2.79]), and the risk increased statistically significantly across quartiles of serum 25(OH) vitamin D concentration (P for trend = 0.016). This association was independent of number of falls, physical function, frailty, renal function, and sex-steroid hormone levels and seemed to be partially mediated by bone resorption.
Limitations:
Few case-patients were nonwhite women. Bone mineral density and parathyroid hormone levels were not accounted for in the analysis.
Conclusion:
Low serum 25(OH) vitamin D concentrations are associated with a higher risk for hip fracture.
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Author, Article and Disclosure Information
From University of Pittsburgh, Pittsburgh, Pennsylvania; University of Washington, Seattle, Washington; University of California, San Francisco, and San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California; University of California, Davis, Davis, California; Ohio State University, Columbus, Ohio; University of Southern California, Los Angeles, California; Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts;
University at Buffalo, Buffalo, New York; University of Wisconsin-Madison, Madison, Wisconsin; and University of Massachusetts Amherst, Amherst, Massachusetts.
Acknowledgment: The authors thank the WHI investigators. For a list of WHI investigators, see the Appendix.
Grant Support: By the National Heart, Lung and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services. Additional support was provided by U.S. Public Health Service Research grants AR052105 and AR048919. Dr. Lee is supported by National Center for Research Resources grant UL 1 RR024146.
Disclosures:Consultancies: J.A. Cauley (Novartis, Eli Lilly), D.C. Bauer (Merck, Roche Diagnostics), J. Wactawski-Wende (Johnson & Johnson), S.R. Cummings (Eli Lilly, Procter & Gamble, Amgen, GlaxoSmithKline, Zelos). Honoraria: J.A. Cauley (Eli Lilly), R.D. Jackson (Sanofi-Aventis, Procter & Gamble), J. Wactawski-Wende (Merck), S.R. Cummings (Eli Lilly). Stock ownership or options (other than mutual funds): M.S. LeBoff (Amgen, General Electric). Expert testimony: S.R. Cummings (Eli Lilly). Grants received: J.A. Cauley (Merck, Pfizer, Novartis), D.C. Bauer (Novartis, Amgen, Procter & Gamble, Merck), R.D. Jackson (MicroMRI, Procter & Gamble), M.S. LeBoff (Abbott), J. Ockene (National Heart, Lung, and Blood Institute), S.R. Cummings (Amgen, Eli Lilly).
Reproducible Research Statement:Study protocol: WHI study protocols are available at whiscience.org. Statistical code and data set: Not available.
Corresponding Author: Jane A. Cauley, DrPH, University of Pittsburgh, Department of Epidemiology, 130 DeSoto Street, Crabtree A524, Pittsburgh, PA 15261; e-mail, [email protected]
Current Author Addresses: Dr. Cauley: University of Pittsburgh, Department of Epidemiology, 130 DeSoto Street, Crabtree A524, Pittsburgh, PA 15261.
Dr. LaCroix, Ms. L. Wu, and Ms. C. Wu: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109.
Dr. Horwitz: University of Pittsburgh Medical Center, Falk 580, 3601 Fifth Avenue, Pittsburgh, PA 15261.
Dr. Danielson: University of Pittsburgh, Department of Epidemiology, 130 DeSoto Street, Crabtree A543, Pittsburgh, PA 15261.
Dr. Bauer: University of California, San Francisco, 185 Berry Street, #5700, San Francisco, CA 94105.
Dr. Lee: University of California, Davis, 4150 V Street, Suite 6400, Sacramento, CA 75817.
Dr. Jackson: The Ohio State University, 485 McCampbell Hall, 1581 Dodd Drive, Columbus, OH 43210.
Dr. Robbins: Lawrence J. Ellison Ambulatory Care Center, 4860 Y Street, Sacramento, CA 95817.
Dr. Stanczyk: USC Keck School of Medicine, Women's & Children's Hospital, 1240 North Mission Road, Room 1M2, Los Angeles, CA 90033.
Dr. LeBoff: Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115.
Dr. Wactawski-Wende: State University of New York at Buffalo, 270 Farber Hall, Buffalo, NY 14214.
Dr. Sarto: University of Wisconsin-Madison, 700 Regent Street, Madison, WI 53715.
Dr. Ockene: University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655.
Dr. Cummings: San Francisco Coordinating Center, 185 Berry Street, Lobby 4, Suite 5700, San Francisco, CA 94107.
Author Contributions: Conception and design: J.A. Cauley, D.C. Bauer, R.D. Jackson, M.S. LeBoff, J. Wactawski-Wende, S.R. Cummings.
Analysis and interpretation of the data: J.A. Cauley, A.Z. LaCroix, M. Horwitz, L. Wu, D.C. Bauer, J.S. Lee, R.D. Jackson, C. Wu, M.S. LeBoff, G. Sarto.
Drafting of the article: J.A. Cauley, L. Wu, M. Horwitz, M.E. Danielson, M.S. LeBoff.
Critical revision of the article for important intellectual content: A.Z. LaCroix, L. Wu, M. Horwitz, M.E. Danielson, D.C. Bauer, J.S. Lee, R.D. Jackson, F.Z. Stanczyk, M.S. LeBoff, J. Wactawski-Wende, G. Sarto, S.R. Cummings.
Final approval of the article: J.A. Cauley, A.Z. LaCroix, L. Wu, M. Horwitz, M.E. Danielson, D.C. Bauer, R.D. Jackson, J.A. Robbins, F.Z. Stanczyk, J. Wactawski-Wende, J. Ockene, S.R. Cummings.
Provision of study materials or patients: J.A. Cauley, J.S. Lee, R.D. Jackson, J.A. Robbins, F.Z. Stanczyk, J. Wactawski-Wende, G. Sarto, J. Ockene.
Statistical expertise: L. Wu.
Obtaining of funding: J.A. Cauley, M.E. Danielson, J.S. Lee, R.D. Jackson, J.A. Robbins, J. Wactawski-Wende, J. Ockene, S.R. Cummings.
Administrative, technical, or logistic support: J.A. Cauley, M.E. Danielson, J.S. Lee, R.D. Jackson, J. Wactawski-Wende.
Collection and assembly of data: J.A. Cauley, A.Z. LaCroix, J.S. Lee, R.D. Jackson, J.A. Robbins, J. Wactawski-Wende, G. Sarto, J. Ockene.
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