High bone concentrations of homocysteine are associated with altered bone morphology in humans

Abstract

Accumulation of homocysteine and S-adenosylhomocysteine in bone has been shown to be associated with reduced bone quality in rats. The aim of the present study was to investigate whether high bone concentrations of homocysteine and S-adenosylhomocysteine as well as a low methylation capacity are related to an impaired bone morphology in humans. Concentrations of homocysteine and its precursors S-adenosylhomocysteine and S-adenosylmethionine were measured in femoral bone samples of eighty-two males and females (age 71 (SD 8) years) who underwent elective hip arthroplasty. Cancellous bone structure was analysed by histomorphometry. In addition, blood was sampled to measure serum concentrations of homocysteine. Results of bone and serum analyses were grouped for individuals with high or low bone concentrations of homocysteine, S-adenosylhomocysteine and S-adenosylmethionine, as well as for individuals with a high or a low methylation capacity, which is indicated by a low or a high S-adenosylhomocysteine:S-adenosylmethionine ratio (n 41, each). Histomorphometry showed a higher trabecular separation and a lower trabecular thickness, trabecular number and trabecular area in individuals with high bone concentrations of homocysteine and S-adenosylhomocysteine compared with individuals with low bone concentrations of homocysteine and S-adenosylhomocysteine. There was no association between the S-adenosylhomocysteine:S-adenosylmethionine ratio and bone morphology. It was found that 48 % of bone homocysteine was bound to the collagen of the extracellular bone matrix. Blood analyses demonstrated a significant correlation between serum and bone homocysteine. The results of the present study indicate an association between altered bone morphology and elevated bone concentrations of homocysteine and S-adenosylhomocysteine, but not between altered bone morphology and methylation capacity.Key words: Homocysteine: S-adenosylhomocysteine: S-adenosylmethionine: Histomorphometry: Bone morphologyThe aim of the present study was to investigate whether high tissue concentrations of homocysteine (HCY) and its precursors S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) in human bone are associated with altered bone morphology. Additionally, we aimed to assess the association between cancellous bone structure and methylation capacity, which is indicated by the SAH:SAM ratio.In rats, high bone concentrations of HCY and SAH as well as an increased SAH:SAM ratio have been shown to be associated with a reduced bone quality (1) . A recently publishedin vitro study has further demonstrated that decreased SAMdependent methylation impairs osteoblast differentiation (2) .Therefore, our hypothesis was that high bone concentrations of HCY and SAH, an increased SAH:SAM ratio as well as a low bone concentration of SAM are associated with a deteriorated cancellous bone structure also in humans. Methods Study designWe harvested cancellous bone samples at the femoral neck of eighty-two osteoarthritis patients undergoing hip arthroplast...

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