This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by LeBoff, M. S. Articles by Cummings, S. Search for Related Content PubMed PubMed Citation Articles by LeBoff, M. S. Articles by Cummings, S. Related Collections Calcium and Bone Metabolism Female Endocrinology

Homocysteine Levels and Risk of Hip Fracture in Postmenopausal Women

Brigham and Women’s Hospital (M.S.L., R.N.), and Harvard Medical School (M.S.L.), Boston, Massachusetts 02115; Fred Hutchinson Cancer Research Center (A.L., L.W., C.K.), Seattle, Washington 98109; College of Medicine and Public Health (R.J.), Ohio State University, Columbus, Ohio 43210; University of California, Davis (J.L.), Davis, California 95616; San Francisco Coordinating Center (D.C.B., S.C.), California Pacific Medical Center Research Institute, San Francisco, California 94115; University of Pittsburgh (J.C.), Pittsburgh, Pennsylvania 15260; University of California, San Francisco (D.C.B., S.C.), San Francisco, California 94102; MedStar Research Institute (A.M.T.), Washington, D.C. 20783; Sinai Hospital of Baltimore (A.M.T.), Baltimore, Maryland 21215; and University of Alabama at Birmingham (C.L.), Birmingham, Alabama 35233

Address all correspondence and requests for reprints to: Meryl S. LeBoff, M.D., Director, Skeletal Health and Osteoporosis Center, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115. E-mail: mleboff{at}partners.org.

Background: Recent studies suggest that high homocysteine levels are associated with an increased risk of fractures. Homocysteine levels are known to be influenced by vitamin B and folate supply or status, and poor renal function can result in higher levels independent of nutritional adequacy.

Objective: The aim of the study was to determine the associations between fasting homocysteine levels and incident hip fractures, and the effects of other factors on hip fracture risk.

Design: We conducted a case-control study in the Women’s Health Initiative Observational Study, a study of postmenopausal women (n = 93,676) recruited in the United States. We selected 400 incident cases of hip fracture and 400 controls matched on age, ethnicity, and blood draw date among women not on osteoporosis therapies. Outcome measures included physician-adjudicated, incident hip fractures. Baseline lifestyle and nutritional questionnaires were performed.

Results: The risk of hip fracture increased 1.38-fold [95% confidence interval (CI), 1.14, 1.66] for each SD increase in serum homocysteine level after adjustment for fracture risk factors. This association was not affected by adjustment for dietary folate, B6, or B12 intake, but it diminished after adjustment for cystatin-C level (odds ratio, 1.08; 95% CI, 0.66–1.79), a measure of renal function not affected by muscle mass. Among women in the highest quartile of homocysteine and cystatin-C compared to those without elevations in either biomarker, the risk of hip fracture was substantially elevated (odds ratio, 2.8; 95% CI, 1.61–4.87).

Conclusions: This study indicates that high homocysteine levels are associated with an increased risk of hip fracture, which could be accounted for by poor renal function.