Perturbations in factors that modulate osteoblast functions in vitamin B6 deficiency

It was hypothesized that the widespread structural defect of collagen in co nnective tissue of vitamin B-6 deficient-animals and the consequent alterat ion in bone biomechanical properties cause an additional stress to their in flammed swollen tibiotarsometatarsal joints. The present study showed a 32% elevation (P < 0.02) in mean plasma free cortisol concentration. Vitamin D metabolism was impaired but without changing plasma calcium homeostasis an d bone mineral content. Mean plasma calcitriol [1,25(OH)(2)D] concentration was significantly reduced (P <less than> 0.001). Because plasma calcidiol concentration did not change, we speculated that either renal 25-hydroxycal ciferol-1 alpha -hydroxylase activity was reduced or 1,25(OH)(2)D turnover was increased. Plasma osteocalcin, an index of osteoblast function related to bone formation, was significantly decreased (P < 0.05). This adverse eff ect on osteoblasts was consistent with the reduction of bone specific alkal ine phosphatase activity (another index of bone formation) found in a previ ous study. The excess of cortisol may have impaired these bone cells functi ons directly and (or) indirectly via the decline in calcitriol synthesis. P lasma hydroxyproline concentrations in B-6-deficient animals were found to be significantly reduced (P < 0.001), suggesting that cortisol in excess ha d also a suppressive effect on another hydroxylase, namely tissue (mainly b one and liver) prolyl hydroxylase. The bone uncoupling (in formation and re soption) associated with vitamin B-6 deficiency seems to be due to secondar y hypercortisolism and (or) another unknown factors but not related to a ch ange in bone modulators such as IGF-1 and eicosanoids.