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

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

Author information

Office of Dietary Supplements and Department of Nutrition Science, Purdue University, West Lafayette, IN; and
National Center for Health Statistics, CDC, Hyattsville, MD;
Eunice Kennedy Shriver National Institute of Child and Human Development, NIH, Bethesda, MD;
Department of Nutrition Science, Purdue University, West Lafayette, IN; and.
ICF International, Rockville, MD.



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.


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.


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).


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.


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.


DXA; NHANES; bone turnover markers; homocysteine; osteoporosis

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