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Original Article
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Volume 350:2042-2049 May 13, 2004 Number 20
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Homocysteine as a Predictive Factor for Hip Fracture in Older Persons
Robert R. McLean, M.P.H., Paul F. Jacques, D.Sc., Jacob Selhub, Ph.D., Katherine L. Tucker, Ph.D., Elizabeth J. Samelson, Ph.D., Kerry E. Broe, M.P.H., Marian T. Hannan, D.Sc., L. Adrienne Cupples, Ph.D., and Douglas P. Kiel, M.D.

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 by Raisz, L. G.
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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 µmol per liter in men and 12.1±5.3 µmol 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.


Source Information

From the Hebrew Rehabilitation Center for Aged Research and Training Institute (R.R.M., E.J.S., K.E.B., M.T.H., D.P.K.); the Jean Mayer Department of Agriculture Human Nutrition Research Center on Aging, Tufts University (P.F.J., J.S., K.L.T.); the Department of Biostatistics, Boston University School of Public Health (L.A.C.); and the Harvard Medical School Division on Aging (M.T.H., D.P.K.) — all in Boston.

Address reprint requests to Dr. McLean at the Framingham Study, 73 Mt. Wayte Ave., Framingham, MA 01702, or at rmclean{at}mail.hrca.harvard.edu.

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Related Letters:

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. Correspondence

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