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Original Investigation
January 9, 2006

Plasma Total Homocysteine Level and Bone Mineral Density: The Hordaland Homocysteine Study

Author Affiliations

Author Affiliations: Department of Public Health and Primary Health Care (Drs Gjesdal, Vollset, Gjessing, and Tell), LOCUS for Homocysteine and Related Vitamins (Drs Vollset, Ueland, and Tell), and Section of Pharmacology, Institute of Medicine (Drs Ueland and Refsum), University of Bergen, and Department of Rheumatology, Haukeland University Hospital (Dr Gjesdal), Bergen, Norway; Department of Pharmacology, University of Oxford, Oxford, England (Dr Refsum); and Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo (Dr Drevon), and Norwegian Institute of Public Health (Dr Gjessing), Oslo, Norway.

Arch Intern Med. 2006;166(1):88-94. doi:10.1001/archinte.166.1.88

Background  Plasma total homocysteine (tHcy) has been associated with hip fracture but not directly with bone mineral density (BMD). We examined the association of hip BMD with levels of plasma tHcy, folate, and vitamin B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C→T and 1298A→C polymorphisms.

Methods  Bone mineral density was measured between 1997 and 2000 in 2268 men and 3070 women, aged 47 to 50 and 71 to 75 years, from the Hordaland Homocysteine Study cohort. Low BMD was defined as BMD in the lowest quintile for each sex and age group. Linear, logistic, and generalized additive regression models were used.

Results  Plasma levels of tHcy were inversely related to BMD among middle-aged and elderly women (P<.001) but not among men. The multiple adjusted odds ratio for low BMD among subjects with high (≥15 μmol/L [≥2.02 mg/L]) compared with low (<9 μmol/L [<1.22 mg/L]) tHcy level was 1.96 (95% confidence interval, 1.40-2.75) for women and was not significant for men. Additional adjustments for plasma folate level or intake of calcium and vitamin D did not substantially alter the results. Plasma folate level was associated with BMD in women only. We observed no association between BMD and vitamin B12 level or the MTHFR polymorphisms.

Conclusions  Elevated tHcy and low folate levels were associated with reduced BMD in women but not in men. These findings suggest that tHcy may be a potential modifiable risk factor for osteoporosis in women.