Plasma total homocysteine level and bone mineral density: the Hordaland Homocysteine Study.
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 (>or=15 micromol/L [>or=2.02 mg/L]) compared with low (<9 micromol/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.
Gjesdal
Clara Gram
CG
Department of Public Health and Primary Health Care, Institute of Medicine, University of Bergen, and Department of Rheumatology, Haukeland University Hospital, Norway. clara.gjesdal@isf.uib.no
Vollset
Stein Emil
SE
Ueland
Per Magne
PM
Refsum
Helga
H
Drevon
Christian A
CA
Gjessing
Håkon K
HK
Tell
Grethe S
GS
D017677:Age Distribution; D000368:Aged; D015519:Bone Density; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005492:Folic Acid / Q000097:blood; D006403:Hematologic Tests; D006710:Homocysteine / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D017678:Sex Distribution; D014805:Vitamin B 12 / Q000097:blood
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12