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Plasma B Vitamins, Homocysteine, and Their Relation with Bone Loss and Hip Fracture in Elderly Men and Women

Institute for Aging Research (R.R.M., E.J.S., D.P.K., M.T.H.), Hebrew SeniorLife, Boston, Massachusetts 02131; Harvard Medical School (R.R.M., E.J.S., D.P.K., M.T.H.), Boston, Massachusetts 02115; Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University (P.F.J., J.S., K.L.T.), Boston, Massachusetts 02111; and Departments of Epidemiology (L.F.) and Biostatistics (L.A.C.), Boston University School of Public Health, Boston, Massachusetts 02118

Address all correspondence and requests for reprints to: Robert R. McLean, Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, Massachusetts 02131. E-mail: rmclean{at}hrca.harvard.edu.

Context: Elevated homocysteine is a strong risk factor for osteoporotic fractures among elders, yet it may be a marker for low B-vitamin status.

Objective: Our objective was to examine the associations of plasma concentrations of folate, vitamin B12, vitamin B6, and homocysteine with bone loss and hip fracture risk in elderly men and women.

Design: This was a longitudinal follow-up study of the Framingham Osteoporosis Study.

Setting: Community dwelling residents of Framingham, MA, were included in the study.

Participants: A total of 1002 men and women (mean age 75 yr) was included in the study.

Main Outcome Measures: Baseline (1987–1989) blood samples were used to categorize participants into plasma B-vitamin (normal, low, deficient) and homocysteine (normal, high) groups. Femoral neck bone mineral density (BMD) measured at baseline and 4-yr follow-up was used to calculate annual percent BMD change. Incident hip fracture was assessed from baseline through 2003.

Results: Multivariable-adjusted mean bone loss was inversely associated with vitamin B6 (P for trend 0.01). Vitamins B12 and B6 were inversely associated with hip fracture risk (all P for trend < 0.05), yet associations were somewhat attenuated and not significant after controlling for baseline BMD, serum vitamin D, and homocysteine. Participants with high homocysteine (>14 µmol/liter) had approximately 70% higher hip fracture risk after adjusting for folate and vitamin B6, but this association was attenuated after controlling for vitamin B12 (hazard ratio = 1.49; 95% confidence interval 0.91, 2.46).

Conclusions: Low B-vitamin concentration may be a risk factor for decreased bone health, yet does not fully explain the relation between elevated homocysteine and hip fracture. Thus, homocysteine is not merely a marker for low B-vitamin status.