JBMR Online - Journal of Bone and Mineral Research - 22(5):747

¹Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway;

³LOCUS for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway;

⁴Section of Pharmacology, Institute of Medicine, University of Bergen, Bergen, Norway;

⁵Oxford Centre for Gene Function, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom;

⁶Institute of Basic Medical Sciences, Department of Nutrition, University of Oslo, Oslo, Norway;

Dr Ueland has received consulting fees from Nycomed and has been a member of the steering board for both the nonprofit foundation to Promote Research into Functional Vitamin B12 Deficiency and Brevital, a company owned by the foundation. He is also an inventor listed on a patent owned by Brevital entitled “Determination of Folate in Fresh and Stored Serum or Plasma as Paraaminobenzoylglutamate.” All other authors state that they have no conflicts of interest.

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 B₁₂ 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 B₁₂ are associated with risk of osteoporosis and fracture. We examined whether plasma levels of tHcy, folate, and vitamin B₁₂ and the methylenetetrahydrofolate reductase (MTHFR) 677C→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 B₁₂ and for different genotypes.

Results: Over a median follow-up period of 12.6 yr, hip fracture was recorded in 184 (7.0%) women and 90 (4.2%) men. The adjusted hazard ratio (95% CI) for fracture in subjects with high (≥15 μM) compared with low levels (<9.0 μM) 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 B₁₂ 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 B₁₂ 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.

Cited by

Markus Herrmann, Britt Wildemann, Alexandra Wagner, Martin Wolny, Heike Schorr, Omid Taban-Shomal, Natalia Umanskaya, Steffen Ross, Patric Garcia, Ulrich Hübner and Wolfgang Herrmann. (2009) Experimental Folate and Vitamin B₁₂ Deficiency Does Not Alter Bone Quality in Rats. Journal of Bone and Mineral Research 24:4, 589-596
Online publication date: 1-Apr-2009.
Abstract | Full Text | Printable PDF (685 KB)

Colin D Steer, Pauline M Emmett, Sarah J Lewis, George Davey Smith and Jon H Tobias. (2009) Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism Is Associated With Spinal BMD in 9-Year-Old Children. Journal of Bone and Mineral Research 24:1, 117-124
Online publication date: 1-Jan-2009.
Abstract | Full Text | Printable PDF (628 KB)