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

Am J Clin Nutr. 2015 Sep;102(3):687-94. doi: 10.3945/ajcn.115.108787. Epub 2015 Jul 29.


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 μg/L; urinary N-terminal cross-linked 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.

Keywords: DXA; NHANES; bone turnover markers; homocysteine; osteoporosis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Absorptiometry, Photon
  • Aged
  • Biomarkers / blood
  • Bone Density*
  • Creatinine / blood
  • Cross-Sectional Studies
  • Female
  • Folic Acid / blood
  • Homocysteine / blood
  • Humans
  • Methylmalonic Acid / blood
  • Middle Aged
  • Nutrition Surveys
  • Nutritional Status
  • Osteoporosis / blood
  • Osteoporosis / epidemiology*
  • Risk Factors
  • United States / epidemiology
  • Vitamin B Complex / blood*


  • Biomarkers
  • Homocysteine
  • Vitamin B Complex
  • Methylmalonic Acid
  • Folic Acid
  • Creatinine