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.