title: B-vitamin status and bone mineral density and risk of lumbar osteoporosis in older females in the United States.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Office of Dietary Supplements and Department of Nutrition Science, Purdue University, West Lafayette, IN; and baileyr@mail.nih.gov.
authors.forename: Regan L
authors.initials: RL
authors.lastname: Bailey
authors.affiliation: National Center for Health Statistics, CDC, Hyattsville, MD;
authors.forename: Anne C
authors.initials: AC
authors.lastname: Looker
authors.affiliation: Eunice Kennedy Shriver National Institute of Child and Human Development, NIH, Bethesda, MD;
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Eunice Kennedy Shriver National Institute of Child and Human Development, NIH, Bethesda, MD;
authors.forename: Ruzong
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN; and.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Eicher-Miller
authors.affiliation: ICF International, Rockville, MD.
authors.forename: Tala H
authors.initials: TH
authors.lastname: Fakhouri
authors.affiliation: National Center for Health Statistics, CDC, Hyattsville, MD;
authors.forename: Jaime J
authors.initials: JJ
authors.lastname: Gahche
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN; and.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Weaver
authors.affiliation: Eunice Kennedy Shriver National Institute of Child and Human Development, NIH, Bethesda, MD;
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D009749:Nutrition Surveys; D009752:Nutritional Status; D010024:Osteoporosis / Q000097:blood / Q000453:epidemiology*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014803:Vitamin B Complex / Q000097:blood*
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D014803:Vitamin B Complex; D008764:Methylmalonic Acid; D005492:Folic Acid; D003404:Creatinine
keywords: DXA; NHANES; bone turnover markers; homocysteine; osteoporosis