Homocysteine levels and risk of hip fracture in postmenopausal women.
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.


METHODS
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.
Leboff
Meryl S
MS
Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA. mleboff@partners.org
Narweker
Rupali
R
LaCroix
Andrea
A
Wu
Lieling
L
Jackson
Rebecca
R
Lee
Jennifer
J
Bauer
Douglas C
DC
Cauley
Jane
J
Kooperberg
Charles
C
Lewis
Cora
C
Thomas
Asha M
AM
Cummings
Steven
S
D000368:Aged; D000428:Alcohol Drinking; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications*; D008875:Middle Aged; D017698:Postmenopause; D012307:Risk Factors; D012907:Smoking
D015415:Biomarkers; D006710:Homocysteine