Role of calcitriol in prevention of osteoporosis: Part I.

Prevention of postmenopausal osteoporosis is an alternative to the currently problematic goal of reversing the trabecular plate thinning and perforation that constitute the major pathologic defects in patients with established osteoporosis. 1,25(OH)2D3 (calcitriol) has been suggested as a drug that may decrease bone resorption sufficiently to preserve trabecular structure in perimenopausal women. In the present study, we compared the effects of calcitriol and an investigational analog, 1,25,26-(OH)3delta22-D3 (Ro-23-8525), to those of an inert vehicle in maintaining the bone mass of oophorectomized adult beagles. In these studies, we used dual-energy radiography to serially quantitate the bone density of control and treated animals. Treatment for 1 year with either agent resulted in no evidence of hypercalcemia or decreased renal function. Moreover, calcitriol and Ro-23-8525 effectively abolished the loss of bone mass observed in untreated oophorectomized controls. Indeed, treated animals displayed variations in bone density similar to that observed in sham-operated untreated animals. These data suggest that calcitriol and Ro-23-8525 may be potentially effective agents for prophylaxis of postmenopausal osteoporosis.