Homocysteine Levels and the Risk of Osteoporotic Fracture

Joyce B.J. Van Meurs, Rosalie A.M. Dhonukshe-Rutten, Saskia M.F. Pluijm, Marjolein Van Der Klift, Robert De Jonge, Jan Lindemans, Lisette C.P.G.M. De Groot, Albert Hofman, Jacqueline C.M. Witteman, Johannes P.T.M. Van Leeuwen, Monique M.B. Breteler, Paul Lips, Huibert A.P. Pols, André G. Uitterlinden

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

656 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)2033-2041+2113
TijdschriftNew England Journal of Medicine
Nummer van het tijdschrift20
StatusGepubliceerd - 13 mei 2004
Extern gepubliceerdJa


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