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Cited by 589Bone health and osteoporosis researchFolate and B Vitamins ResearchHip and Femur Fractures

Homocysteine as a Predictive Factor for Hip Fracture in Older Persons

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McLean, Robert R., Jacques, Paul F., Selhub, Jacob, Tucker, Katherine L., Samelson, Elizabeth J., Broe, Kerry E., Hannan, Marian T., Cupples, L. Adrienne +1 more·2004·New England Journal of Medicine
DOI 10.1056/nejmoa032739
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Abstract

BACKGROUND: The increased prevalence of osteoporosis among people with homocystinuria suggests that a high serum homocysteine concentration may weaken bone by interfering with collagen cross-linking, thereby increasing the risk of osteoporotic fracture. We examined the association between the total homocysteine concentration and the risk of hip fracture in men and women enrolled in the Framingham Study. METHODS: We studied 825 men and 1174 women, ranging in age from 59 to 91 years, from whom blood samples had been obtained between 1979 and 1982 to measure plasma total homocysteine. The participants in our study were followed from the time that the sample was obtained through June 1998 for incident hip fracture. Sex-specific, age-adjusted incidence rates of hip fracture were calculated for quartiles of total homocysteine concentrations. Cox proportional-hazards regression was used to calculate hazard ratios for quartiles of homocysteine values. RESULTS: The mean (+/-SD) plasma total homocysteine concentration was 13.4+/-9.1 micromol per liter in men and 12.1+/-5.3 micromol per liter in women. The median duration of follow-up was 12.3 years for men and 15.0 years for women. There were 41 hip fractures among men and 146 among women. The age-adjusted incidence rates per 1000 person-years for hip fracture, from the lowest to the highest quartile for total homocysteine, were 1.96 (95 percent confidence interval, 0.52 to 3.41), 3.24 (0.97 to 5.52), 4.43 (1.80 to 7.07), and 8.14 (4.20 to 12.08) for men and 9.42 (5.72 to 13.12), 7.01 (4.29 to 9.72), 9.58 (6.42 to 12.74), and 16.57 (11.84 to 21.30) for women. Men and women in the highest quartile had a greater risk of hip fracture than those in the lowest quartile--the risk was almost four times as high for men and 1.9 times as high for women. CONCLUSIONS: These findings suggest that the homocysteine concentration, which is easily modifiable by means of dietary intervention, is an important risk factor for hip fracture in older persons.

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  • A type I collagen α1 first-intron polymorphism and high homocysteine can affect fracture risk independently of BMD.

    “A polymorphism of the first intron of the gene coding for the type I collagen α1 chain and increased levels of homocysteine can influence fracture risk independent of BMD”

    From Pathogenesis of osteoporosis: concepts, conflicts, and prospects (2005) · cites this paper as [100]

    The results passage (indexed under “covariables”; page unavailable) associates higher homocysteine levels with greater hip-fracture risk in older men and women. The discussion says baseline BMD data were unavailable, so the study could not determine whether that association was independent of BMD. The paper does not address the claimed type I collagen α1 first-intron polymorphism. (LLM, conf=0.91)

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Cites

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Cited by

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Authors
McLean, R. R., Jacques, P. F., Selhub, J., Tucker, K. L., Samelson, E. J., Broe, K. E., Hannan, M. T., Cupples, L. A., & Kiel, D. P.
Affiliations
  • Harvard University (US)
  • Tufts University (US)
  • Boston University (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2004-05-13
Volume
350
Issue
20
Pages
2042-2049
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa032739
OpenAlex
W2042577535
Cited by
589
References
2
Citations by year
2026: 2 · 2025: 8 · 2024: 6 · 2023: 10 · 2022: 13 · 2021: 20 · 2020: 18 · 2019: 14 · 2018: 15 · 2017: 15 · 2016: 16 · 2015: 26 · 2014: 26 · 2013: 37 · 2012: 24
FWCI
57.88
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (n01hc25195-41-0-1)
  • National Heart, Lung, and Blood Institute (HL54776, N01‐HC25195, R01HL054776)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR/AG 41398)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Surgery › Hip and Femur Fractures
Keywords
homocysteine, hip fracture, osteoporotic fractures, older adults, fracture risk prediction, sex differences, Framingham Heart Study, bone health, collagen cross-linking, hyperhomocysteinemia, osteoporosis, menopause, estrogen deficiency, vitamin B12 deficiency, folate deficiency, vitamin B6 deficiency
MeSH terms
Aged, Aged, 80 and over, Female, Follow-Up Studies, Hip Fractures, Homocysteine, Humans, Male, Middle Aged, Osteoporosis, Risk Factors, Incidence, Proportional Hazards Models, Hyperhomocysteinemia

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