Plasma homocysteine, folate, and vitamin B12 and the risk of hip fracture:: The hordaland homocysteine study

Homocysteine and related factors were evaluated as risk factors for subsequent hip fractures among 4766 elderly men and women. High levels of homocysteine and low levels of folate predicted fracture, whereas vitamin B-12 and genotypes were not related to fracture risk. High homocysteine may be a modifiable risk factor for hip fracture. Introduction: Elevated plasma total homocysteine (tHcy) and deficiencies of folate and vitamin B-12 are associated with risk of osteoporosis and fracture. We examined whether plasma levels of tHcy, folate, and vitamin B-12 and the methylenetetrahydrofolate reductase (MTHFR) 677C -> T)T and 1298C -> T polymorphisms predicted hip fracture. Materials and Methods: This was a population-based prospective study of 2639 women and 2127 men who were 65-67 yr at enrollment in 1992-1993. Information on hip fracture was obtained from computerized records of discharge diagnoses from all hospitalizations in the region in the period between enrollment and November 30, 2005. Cox proportional hazard regression was used to estimate fracture risk according to levels of plasma tHcy, folate, and vitamin 13, and for different genotypes. Results: Over a median follow-up period of 12.6 yr, hip fracture was recorded in 1.84 (7.0%) women and 90 (4.2%) men. The adjusted hazard ratio (95% CI) for fracture in subjects with high (>= 15 mu M) compared with low levels (< 9.0 mu M) of tHcy was 2.42 (1.43-4.09) among women and 1.37 (0.63-2.98) among men. Dose response analyses indicated a positive association between plasma tHcy and risk of fracture in both sexes and a negative association between plasma folate and risk of fracture among women only. Plasma vitamin B12 level or MTHFR genotype was not significantly related to risk of fracture after adjustments for confounding factors. The association between tHcy and risk of hip fracture was only slightly weakened by adjustments for plasma levels of vitamin B-12 and folate. Conclusions: tHcy seems to be a predictor for hip fracture among elderly men and women. Folate was a predictor among women only, whereas vitamin B-12 and MTHFR genotype did not predict hip fracture. Our data corroborate the hypothesis that homocysteine may play a role in the pathogenesis of osteoporotic fractures.