Perturbations in factors that modulate osteoblast functions in vitamin B6 deficiency

Abstract

It was hypothesized that the widespread structural defect of collagen in connective tissue of vitamin B6deficient-animals and the consequent alteration in bone biomechanical properties cause an additional stress to their inflammed swollen tibiotarsometatarsal joints. The present study showed a 32% elevation (P &lt 0.02) in mean plasma free cortisol concentration. Vitamin D metabolism was impaired but without changing plasma calcium homeostasis and bone mineral content. Mean plasma calcitriol [1,25(OH)2D] concentration was significantly reduced (P < 0.001). Because plasma calcidiol concentration did not change, we speculated that either renal 25-hydroxycalciferol-1α-hydroxylase activity was reduced or 1,25(OH)2D turnover was increased. Plasma osteocalcin, an index of osteoblast function related to bone formation, was significantly decreased (P < 0.05). This adverse effect on osteoblasts was consistent with the reduction of bone specific alkaline phosphatase activity (another index of bone formation) found in a previous study. The excess of cortisol may have impaired these bone cells functions directly and (or) indirectly via the decline in calcitriol synthesis. Plasma hydroxyproline concentrations in B6-deficient animals were found to be significantly reduced (P < 0.001), suggesting that cortisol in excess had also a suppressive effect on another hydroxylase, namely tissue (mainly bone and liver) prolyl hydroxylase. The bone uncoupling (in formation and resoption) associated with vitamin B6deficiency seems to be due to secondary hypercortisolism and (or) another unknown factors but not related to a change in bone modulators such as IGF-1 and eicosanoids.Key words: collagen, vitamin B6, vitamin D, cortisol, osteocalcin, IGF-1, eicosanoids, PGE2.