Response of rachitic rat bones to 1,25-dihydroxyvitamin D3: biphasic effects on mineralization and lack of effect on bone resorption.

Rachitic rats, maintained on a diet adequate in Ca and P, were treated daily with varying amounts of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. At low levels (1 ng/day) 1,25-(OH)2D3 sustained a healing response equivalent to that of 25-hydroxyvitamin D3 (100 ng/day) or the parent vitamin. Above 5 ng/day administration of 1,25-(OH)2D3 resulted in an accumulation of osteoid, giving a histological appearance similar to vitamin D deficiency. The effects of 1,25-(OH)2D3 on bone did not correlate with changes in plasma Ca or inorganic phosphorus; doses that were effective in raising bone ash and reducing the amount of osteoid failed to normalize plasma Ca, whilst the amount of sterol required to normalize plasma Ca was excessive in terms of the effect on bone. 1,25-(OH)2D3 did not stimulate any of the histological parameters of bone resorption. We conclude that 1,25-(OH)2D3 can effectively heal the bone lesions of vitamin D deficiency, but that, at high concentrations, the sterol can inhibit mineralization. Furthermore, these results question the accepted role of 1,25-(OH)2D3 as a regulator of bone resorption in vivo.