2β-(3-Hydroxypropoxy) 1α, 25-Dihydroxyvitamin D₃(ED-71), increases bone mass by stimulating bone formation in hypophosphatemic mice

Abstract

To determine the effects of ED-71, a new active vitamin D₃ analogue, on bone, we examined the action of ED-71 and 1α, 25(OH)₂D₃, using hypophosphatemic (Hyp) mice, a model for X-linked hypophosphatemic rickets in humans. ED-71 has the unique characteristics of a longer half-life in serum, a higher binding affinity to serum vitamin D binding protein and lower affinity to the vitamin D receptor than 1α, 25(OH)₂D₃. Hyp mice were treated with 10-1200 pmol/kg/day of ED-71, 40-400 pmol/kg/day of 1α, 25(OH)₂D₃, or the vehicle alone, administered daily for 21 days by subcutaneous injection. ED-71 at doses of 100-400 pmol/kg/day, dose-dependently effects in increased bone size and bone mineral density (BMD) without causing hypercalcemia. However 1α, 25(OH)₂D₃ at a dese of 400 pmol/kg/day, demonstrated only slight increases in bone size and BMD with hypercalcemia. These findings suggest that ED-71 may be more beneficial in the treatment of X-linked hypophosphatemic rickets than 1α, 25(OH)₂D₃.