24R,25-dihydroxyvitamin D-3: An essential vitamin D-3 metabolite for both normal bone integrity and healing of tibial fracture in chicks

We tested the hypothesis that 24R,25-dihydroxyvitamin D-3 [24R,25-(OH)(2)D-3] is an essential vitamin D metabolite for the development of normal bone integrity and the healing of fractures. The natural 24R,25-(OH)(2)D-3 and its synthetic epimer 24S,25-dihydroxyvitamin D-3 [24S,25-(OH)(2)D-3] were tested alone or in combination with 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25-(OH)(2)D-3], on normal bone development and other related variables of the Ca2+ homeostasis system [serum Ca2+, 25-hydroxyvitamin D-3 (25OHD(3)), 24,25-(OH)(2)D-3, and 1 alpha,25-(OH)(2)D-3 levels] in chicks. Mechanical testing of torsional strength was carried out on the femur. 24R,25-(OH)(2)D-3 (80 nmol/kg diet) alone was sufficient for normal bone growth and integrity similar to that achieved by the vitamin D-3-replete controls. Next, chicks were fed a 25OHD(3)-replete diet (75 nmol/kg diet) for 8 days after hatching, and then 25OHD(3) was withdrawn to minimize any residual circulating metabolites before the imposition of standardized tibial fractures 14 days later. Vitamin D metabolites were administered for 2 weeks to determine their effects on the mechanical properties of healed tibia. 24S,25-(OH)(2)D-3 combined with 1 alpha,25-(OH)(2)D-3 or 1 alpha,25-(OH)(2)D-3 alone resulted in poor healing [strength values of 0.158 +/- 0.011 and 0.123 +/- 0.009 Nm (Newton.meter), respectively] compared with that in the 25OHD(3)-treated control group (0.374 +/- 0.029 Nm). In contrast, the fractured tibia of the birds fed 24R,25(OH)(2)D-3 in combination with 1 alpha,25-(OH)(2)D-3 showed healing equivalent to that in the control group, with strength values of 0.296 +/- 0.043 Nm. These results suggest that when 24R,25-(OH)(2)D-3 is present at normal physiological concentrations, it is an essential vitamin D-3 metabolite for both normal bone integrity and healing of fracture in chicks.