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: 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: Longitudinal follow-up study of the Framingham Osteoporosis Study.

Setting: Community-dwelling residents of Framingham, Massachusetts.

Participants: 1,002 men and women (mean age 75 years).

Main Outcome Measures: Baseline (1987–89) 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 four-year 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 directly 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/L) had 70% higher hip fracture risk after adjusting for folate and vitamin B6, but this association was attenuated after controlling for vitamin B12 (HR=1.49; 95% CI 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.