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Methylation capacity not involved in homocysteine–fracture link
By MedWire Reporters
03 April 2012
Bone 2012; Advance online publication

MedWire News: The link between homocysteine levels and osteoporotic fractures does not appear to be mediated by methylation capacity, research shows.

However, the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), both markers of methylation capacity, did independently predict bone mineral density (BMD) at the femoral neck.

"To the best of our knowledge, circulating levels of SAM/SAH-ratio have not been investigated previously in relation to osteoporotic fracture risk in humans," write Anke Enneman (Erasmus Medical Center, Rotterdam, the Netherlands) and colleagues in Bone.

They explain that mildly elevated levels of homocysteine are associated with osteoporotic fractures, but the mechanism is not entirely clear. Animal models have suggested that homocysteine might disrupt DNA methylation and gene expression and this in turn might alter bone structure.

Enneman and colleagues therefore tested the hypothesis that altered methylation capacity might play a role in bone metabolism.

Using data from a large Dutch population-based study, the researchers measured plasma levels of homocysteine, SAH, and SAM in 503 women aged 55 years and above. Over a total of 3502 person-years of follow-up, 103 of the women sustained at least one osteoporotic fracture.

The risk for osteoporotic bone fracture was significantly and positively correlated with homocysteine levels, the researchers report.

For instance, compared with women with homocysteine levels below7.9 µmol/L, those with levels in the range 9.4-11.6 µmol/L had nearly twice the risk for bone fracture (hazard ratio 1.96).

Quartile measurements of SAM, SAH, and SAM/SAH were not associated with the risk for bone fracture, however, although the ratio of the two markers independently predicted hip BMD.

"Alterations in methylation capacity most likely do not appear to be an important factor in the association between homocysteine and fractures," conclude Enneman and colleagues.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

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