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Homocysteine levels and the risk of osteoporotic fracture.

Abstract

BACKGROUND

Very high plasma homocysteine levels are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures.

METHODS

We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects, 55 years of age or older, who participated in two separate prospective, population-based studies. In the Rotterdam Study, there were two independent cohorts: 562 subjects in cohort 1, with a mean follow-up period of 8.1 years; and 553 subjects in cohort 2, with a mean follow-up period of 5.7 years. In the Longitudinal Aging Study Amsterdam, there was a single cohort of 1291 subjects, with a mean follow-up period of 2.7 years. Multivariate Cox proportional-hazards regression models were used for analysis of the risk of fracture, with adjustment for age, sex, body-mass index, and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels.

RESULTS

During 11,253 person-years of follow-up, osteoporotic fractures occurred in 191 subjects. The overall multivariable-adjusted relative risk of fracture was 1.4 (95 percent confidence interval, 1.2 to 1.6) for each increase of 1 SD in the natural-log-transformed homocysteine level. The risk was similar in all three cohorts studied, and it was also similar in men and women. A homocysteine level in the highest age-specific quartile was associated with an increase by a factor of 1.9 in the risk of fracture (95 percent confidence interval, 1.4 to 2.6). The associations between homocysteine levels and the risk of fracture appeared to be independent of bone mineral density and other potential risk factors for fracture.

CONCLUSIONS

An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women.

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  • Authors+Show Affiliations

    ,

    Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. j.vanmeurs@erasmusmc.nl

    , , , , , , , , , , , ,

    Source

    The New England journal of medicine 350:20 2004 May 13 pg 2033-41

    MeSH

    Aged
    Bone Density
    Cohort Studies
    Female
    Follow-Up Studies
    Fractures, Bone
    Homocysteine
    Humans
    Hyperhomocysteinemia
    Male
    Middle Aged
    Osteoporosis
    Proportional Hazards Models
    Risk
    Risk Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15141041

    Citation

    van Meurs, Joyce B J., et al. "Homocysteine Levels and the Risk of Osteoporotic Fracture." The New England Journal of Medicine, vol. 350, no. 20, 2004, pp. 2033-41.
    van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004;350(20):2033-41.
    van Meurs, J. B., Dhonukshe-Rutten, R. A., Pluijm, S. M., van der Klift, M., de Jonge, R., Lindemans, J., ... Uitterlinden, A. G. (2004). Homocysteine levels and the risk of osteoporotic fracture. The New England Journal of Medicine, 350(20), pp. 2033-41.
    van Meurs JB, et al. Homocysteine Levels and the Risk of Osteoporotic Fracture. N Engl J Med. 2004 May 13;350(20):2033-41. PubMed PMID: 15141041.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Homocysteine levels and the risk of osteoporotic fracture. AU - van Meurs,Joyce B J, AU - Dhonukshe-Rutten,Rosalie A M, AU - Pluijm,Saskia M F, AU - van der Klift,Marjolein, AU - de Jonge,Robert, AU - Lindemans,Jan, AU - de Groot,Lisette C P G M, AU - Hofman,Albert, AU - Witteman,Jacqueline C M, AU - van Leeuwen,Johannes P T M, AU - Breteler,Monique M B, AU - Lips,Paul, AU - Pols,Huibert A P, AU - Uitterlinden,André G, PY - 2004/5/14/pubmed PY - 2004/5/18/medline PY - 2004/5/14/entrez SP - 2033 EP - 41 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 350 IS - 20 N2 - BACKGROUND: Very high plasma homocysteine levels are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures. METHODS: We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects, 55 years of age or older, who participated in two separate prospective, population-based studies. In the Rotterdam Study, there were two independent cohorts: 562 subjects in cohort 1, with a mean follow-up period of 8.1 years; and 553 subjects in cohort 2, with a mean follow-up period of 5.7 years. In the Longitudinal Aging Study Amsterdam, there was a single cohort of 1291 subjects, with a mean follow-up period of 2.7 years. Multivariate Cox proportional-hazards regression models were used for analysis of the risk of fracture, with adjustment for age, sex, body-mass index, and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels. RESULTS: During 11,253 person-years of follow-up, osteoporotic fractures occurred in 191 subjects. The overall multivariable-adjusted relative risk of fracture was 1.4 (95 percent confidence interval, 1.2 to 1.6) for each increase of 1 SD in the natural-log-transformed homocysteine level. The risk was similar in all three cohorts studied, and it was also similar in men and women. A homocysteine level in the highest age-specific quartile was associated with an increase by a factor of 1.9 in the risk of fracture (95 percent confidence interval, 1.4 to 2.6). The associations between homocysteine levels and the risk of fracture appeared to be independent of bone mineral density and other potential risk factors for fracture. CONCLUSIONS: An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women. SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/15141041/Homocysteine_levels_and_the_risk_of_osteoporotic_fracture_ L2 - https://www.nejm.org/doi/10.1056/NEJMoa032546?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=www.ncbi.nlm.nih.gov DB - PRIME DP - Unbound Medicine ER -