Original Full Length ArticleThe association between plasma homocysteine levels, methylation capacity and incident osteoporotic fractures

BackgroundAn elevated level of plasma homocysteine (Hcy) is a known risk factor for osteoporotic fractures. In addition, Hcy is related to DNA-methylation metabolism. To determine whether the association between Hcy and fractures is explained by an altered methylation capacity, we investigated the associations between levels of s-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and fracture risk.MethodsWe studied 503 females aged 55 years and over from the Rotterdam Study (RS) in whom plasma Hcy, SAM and SAH levels were measured. Bone mineral density (BMD) at the hip was assessed using DXA. Incident fractures were recorded over a mean period of 7.0 years. Cox proportional hazards analysis and linear regression were used to assess relationships between plasma metabolite levels, incident osteoporotic fractures and BMD.ResultsOver a total of 3502 person-years of follow-up, 103 subjects sustained at least one osteoporotic fracture. Whereas incidence of osteoporotic fractures was associated with quartiles of Hcy (p = 0.047), it was not associated with quartiles of SAM, SAH or SAM/SAH-ratio (all p for trend > 0.6). Stepwise linear regression showed that SAM/SAH-ratio, but not Hcy, was independently associated with hip BMD (β = 0.073, p = 0.025).ConclusionSince SAM, SAH and SAM/SAH-ratio were not associated with osteoporotic fractures, alterations in methylation capacity most likely do not appear to be an important factor in the association between Hcy and fractures.

► Plasma Hcy predicts osteoporotic fractures, but not FN-BMD. ► Plasma SAM/SAH-ratio is associated with FN-BMD, but not with osteoporotic fracture incidence. ► Methylation capacity is not likely to be an important factor in the association between Hcy and osteoporotic fracture incidence.