Homocysteine Levels and the Risk of Osteoporotic Fracture
Joyce B.J. van Meurs, Ph.D., Rosalie A.M. Dhonukshe-Rutten, M.Sc., Saskia M.F. Pluijm, Ph.D., Marjolein van der Klift, M.D., Ph.D., Robert de Jonge, Ph.D., Jan Lindemans, Ph.D., Lisette C.P.G.M. de Groot, Ph.D., Albert Hofman, M.D., Ph.D., Jacqueline C.M. Witteman, Ph.D., Johannes P.T.M. van Leeuwen, Ph.D., Monique M.B. Breteler, M.D., Ph.D., Paul Lips, M.D., Ph.D., Huibert A.P. Pols, M.D., Ph.D., and André G. Uitterlinden, Ph.D.
Background Very high plasma homocysteine levels are characteristicof homocystinuria, a rare autosomal recessive disease accompaniedby the early onset of generalized osteoporosis. We thereforehypothesized that mildly elevated homocysteine levels mightbe related to age-related osteoporotic fractures.
Methods We studied the association between circulating homocysteinelevels and the risk of incident osteoporotic fracture in 2406subjects, 55 years of age or older, who participated in twoseparate prospective, population-based studies. In the RotterdamStudy, there were two independent cohorts: 562 subjects in cohort1, with a mean follow-up period of 8.1 years; and 553 subjectsin cohort 2, with a mean follow-up period of 5.7 years. In theLongitudinal Aging Study Amsterdam, there was a single cohortof 1291 subjects, with a mean follow-up period of 2.7 years.Multivariate Cox proportional-hazards regression models wereused for analysis of the risk of fracture, with adjustment forage, sex, body-mass index, and other characteristics that maybe associated with the risk of fracture or with increased homocysteinelevels.
Results During 11,253 person-years of follow-up, osteoporoticfractures occurred in 191 subjects. The overall multivariable-adjustedrelative 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–transformedhomocysteine level. The risk was similar in all three cohorts studied, and it was also similar in men and women.A homocysteinelevel in the highest age-specific quartile was associated withan increase by a factor of 1.9 in the risk of fracture (95 percentconfidence interval, 1.4 to 2.6). The associations between homocysteinelevels and the risk of fracture appeared to be independent ofbone mineral density and other potential risk factors for fracture.
Conclusions An increased homocysteine level appears to be astrong and independent risk factor for osteoporotic fracturesin older men and women.
Source Information
From the Departments of Internal Medicine (J.B.J.M., M.K., J.P.T.M.L., H.A.P.P., A.G.U.), Epidemiology and Biostatistics (A.H., J.C.M.W., M.M.B.B., H.A.P.P., A.G.U.), and Clinical Chemistry (R.J., J.L., A.G.U.), Erasmus Medical Center, Rotterdam; the Division of Human Nutrition, Wageningen University, Wageningen (R.A.M.D.-R., L.C.P.G.M.G.); and the Institute for Research in Extramural Medicine and the Department of Endocrinology, Vrije Universiteit Medical Center, Amsterdam (S.M.F.P., P.L.) — all in the Netherlands.
Address reprint requests to Dr. van Meurs at the Genetics Laboratory, Rm. Ee571, Department of Internal Medicine, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, the Netherlands, or at j.vanmeurs{at}erasmusmc.nl.
Homocysteine as a Predictive Factor for Hip Fracture in Older Persons
Auer J., Lamm G., Eber B., Bursztyn M., Pérez-Castrillón J. L., Arranz-Peña M. L., Luis D. D., Ellenberg S. S., Orloff D. G., Temple R. J., McLean R. R., Kiel D. P., van Meurs J. B.J., Pols H. A.P., Uitterlinden A. G., Raisz L. G.
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N Engl J Med 2004;
351:1027-1030, Sep 2, 2004.
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