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

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.

Hyperhomocysteinemia is not associated with reduced bone quality in humans with hip osteoarthritis.

BACKGROUND: Recent clinical and animal studies suggest that increased serum homocysteine (HCY) concentrations may be a risk factor for osteoporosis. In vitro studies showed that increasing HCY concentrations stimulate the activity of human osteoclasts. However, there is no data demonstrating that circulating HCY is related to structural and biomechanical properties of human bones. This study investigated the relationship between morphological as well as biomechanical bone properties and HCY serum concentrations in humans suffering from hip osteoarthritis (OA). METHODS: Fasting blood samples and femoral heads were obtained from 94 males and females who underwent hip arthroplasty due to OA. Bones were assessed by dual energy X-ray absorptiometry (DXA), biomechanical testing (indentation method), and histomorphometry. Blood was collected for measurement of HCY, folate, vitamin B6, and vitamin B12. Subjects were classified as hyperhomocysteinemic (>12 micromol/L, n=47) and normohomocysteinemic (<12 micromol/L, n=47) according to their serum HCY concentrations. RESULTS: Folate and vitamin B6, but not vitamin B12, were significantly lower in hyperhomocysteinemic subjects compared with controls. However, DXA, biomechanical testing, and histomorphometry did not reveal significant differences in bone quality between hyperhomocysteinemic subjects and controls. CONCLUSIONS: The results of the present study do not indicate a significant relationship between circulating HCY concentrations and morphological or biomechanical bone properties in humans with OA of the hip.

Low serum folate and vitamin B-6 are associated with an altered cancellous bone structure in humans.

BACKGROUND: Several clinical trials have reported B vitamins to be associated with osteoporosis. OBJECTIVE: Our objective was to investigate whether low serum B vitamins are associated with altered structural and biomechanical properties of human bone. DESIGN: Femoral heads of 94 men and women who underwent hip arthroplasty were analyzed by using dual-energy X-ray absorptiometry (DXA), biomechanical testing (indentation method), and histomorphometry. In addition, blood was collected to measure serum concentrations of homocysteine, folate, vitamin B-6, vitamin B-12, the bone formation marker osteocalcin, and the bone resorption marker tartrate-resistant acid phosphatase (TRAP). Measurement outcomes were grouped according to subjects with high and low serum concentrations, respectively, of folate, vitamin B-6, and vitamin B-12 (n = 47 for each group). RESULTS: Histomorphometric analysis showed a significantly lower trabecular thickness and trabecular area in subjects with low serum folate concentrations than in those with high serum folate concentrations and a significantly lower trabecular number in subjects with low serum vitamin B-6 concentrations than in those with high serum vitamin B-6 concentrations. In contrast, we found a comparable trabecular structure in subjects with high and low serum vitamin B-12 concentrations. DXA and biomechanical testing did not show significant differences between subjects with high and low serum B vitamin concentrations. Osteocalcin was significantly lowered in subjects with a low serum B vitamin concentration, whereas there was no association between serum B vitamins and TRAP. CONCLUSION: The results of the present study indicate that low serum folate and vitamin B-6 concentrations, but not low serum vitamin B-12 concentrations, are associated with an altered morphology of human bone.