The biphasic effect of triiodothyronine compared to bone resorbing effect of PTH on bone modelling of mouse long bone in vitro

To examine the effects of T₃ on fetal long bone modelling the radii and ulnae of 16 day old fetal mice were grown in vitro for two days. Their growth, mineralization, and resorption were assessed by measuring diaphyseal length, calcium and phosphorus content, hydroxyproline content, and the release of incorporated ⁴⁵Ca. The effects of T₃ were compared to the effects of 1-34 PTH, a known resorbing agent, on the same system. Devitalized bones were used as a control. The results showed that T₃ had a biphasic effect. At high concentrations (10^-5 M-10^-6 M) T₃ inhibited the growth of the bones as indicated by their diaphyseal length and hydroxyproline content. Calcium and phosphorus content were significantly decreased while ⁴⁵Ca release was increased. Similar effects were also found after the addition of 1-34 PTH to the media. However, T₃, at lower concentrations (10^-7 M-10^-9 M), stimulated the growth and calcification of the bones as indicated by an increase in diaphyseal length and the hydroxyproline, calcium, and phosphorus content. ⁴⁵Ca release was significantly decreased at these concentrations. Neither T₃ nor 1-34 PTH affected devitalized bones in the same system. The results suggest that at physiological concentrations, T₃ has a direct, anabolic effect on bone, which may explain its major role in the growth process of various species. At high doses, however, T₃ stimulates bone resorption in a way similar to PTH.