Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: A 2-y randomized controlled trial

Background: In recent prospective studies, higher homocysteine concentrations were shown to be a risk factor for osteoporotic fractures in older persons. Supplements containing folate and vitamins B-12 and B-6 lower homocysteine concentrations. Objective: The objective of the study was to determine in healthy older persons whether lowering homocysteine with B vitamins affects plasma biomarkers of bone turnover. Design: Healthy older persons (n = 276; aged ≥65 y) were randomly assigned to receive either a daily supplement containing folate (1 mg), vitamin B-12 (500 μg), and vitamin B-6 (10 mg) or a placebo for 2 y. Of these participants, we selected 135 with baseline homocysteine concentrations >15.0 μmol/L, and we measured serum bone-specific alkaline phosphatase, a marker of bone formation, and bone-derived collagen fragments, a marker of bone resorption, at baseline and 2 y later. Results: At 2 y, plasma homocysteine concentrations were 5.2 μmol/L (95% CI: 3.9, 6.6 μmol/L; P < 0.001) lower in the vitamin than in the placebo group. No significant differences were found in either serum bone-specific alkaline phosphatase (-0.3 μg/L; 95% CI: 2.8, 2.1 μg/L; P = 0.79) or bone-derived collagen fragments (0.0 μg/L;95%CI: -0.1, 0.1 μg/L; P = 0.76) between the vitamin and placebo groups, respectively, with 2 y of supplementation. Conclusion: Supplementation with folate and vitamins B-6 and B-12 lowered plasma homocysteine but had no beneficial effect on bone turnover at the end of 2 y, as assessed by biomarkers of bone formation and resorption.