B-vitamin status and bone mineral density and risk of lumbar osteoporosis in older females in the United States

Background: Previous data suggest that elevated serum total homocysteine (tHcy) may be a risk factor for bone fracture and osteoporosis. Nutritional causes of elevated tHcy are suboptimal B-vitamin status. To our knowledge, this is the first nationally representative report on the relation of B vitamins and bone health from a population with folic acid fortification. Objective: The purpose of this analysis was to examine the relation between B-vitamin status biomarkers and bone mineral density (BMD), risk of osteoporosis, and biomarkers of bone turnover. Design: We examined the relation of tHcy, methylmalonic acid (MMA), and serum/red blood cell folate and total-body and lumbar spine BMD in women aged >= 50 y participating in the NHANES 1999-2004 (n = 2806), a nationally representative cross-sectional survey. These are the only years with concurrent measurement of tHcy and whole-body dual-energy X-ray absorptiometry. We also examined B-vitamin biomarkers relative to bone turnover markers, bone alkaline phosphatase, and urinary N-terminal cross-linked telopeptide of type I collagen in a 1999-2002 subset with available data (n = 1813). Results: In comparison with optimal concentrations, women with elevated tHcy were older with lower serum vitamin B-12, red blood cell folate, and dietary micronutrient intakes and had significantly higher mean +/- SE markers of bone turnover (bone alkaline phosphatase: 15.8 +/- 0.59 compared with 14.0 +/- 0.25 mu g/L; urinary N-terminal crosslinked telopeptide of type I collagen: 48.2 +/- 2.9 compared with 38.9 +/- 0.90 nmol bone collagen equivalents per mmol creatinine/L). Elevated MMA (OR: 1.88; 95% CI: 1.10, 3.18) and tHcy (OR: 2.17; 95% CI: 1.14, 4.15) were related to increased risk of lumbar osteoporosis. When examined as a continuous variable, tHcy was negatively associated, serum folates were positively associated, and MMA and vitamin B-12 were not significantly associated with lumbar and total-body BMD. Conclusion: In this nationally representative population of older US women with high exposure to B vitamins through food fortification and dietary supplements, only elevated tHcy and MMA were independently associated with risk of lumbar spine osteoporosis.