Contrasting effects on bone formation and on fracture healing of cholecalciferol and of 1 α-hydroxycholecalciferol

Experimental fractures were performed on tibiae of vitamin D-depleted chicks. The chicks were divided into three groups; they were treated daily with (a) cholecalciferol or (b) 1α-hydroxycholecalciferol (1α(OH)D₃), or (c) they received no treatment. Microscopic examination of the calluses formed at the fractured sites and of the proximal tibiae of the contralateral legs showed that treatment with 1α(OH)D₃ failed to heal most of the rachitic signs seen in the nontreated chicks, despite normal plasma concentrations of calcium and of inorganic phosphorus. In a second experiment, experimental fractures were performed on tibiae of chicks that were fed a vitamin D-deficient diet, but were dosed continuously with radioactive cholecalciferol. Analysis of cholecalciferol metabolites in the callus tissue showed perferential accumulation of 25-hydroxycholecalciferol (25(OH)D₃) and of 24,25-dihydroxycholecalciferol (24,25(OH)₂D₃). Very little 1α, 25-dihydroxycholecalciferol (1α,25(OH)₂D₃) was detected in bones or in calluses. Based on the data obtained, the following conclusions were drawn: (a) that cholecalciferol is directly involved in bone formation; and (b) that 1α, 25(OH)₂D₃ is not the sole metabolite of cholecalciferol involved in this process.