VITAMIN-D METABOLITES AND ANALOGS IN THE TREATMENT OF OSTEOPOROSIS

Objective: To review recent findings on the skeletal actions of vitami n D and to examine results of the latest clinical trials of vitamin D in the treatment of osteoporosis. Options: The vitamin D analog 1-alph a hydroxycholecalciferol (1 alpha-OH-D-3); the vitamin D metabolite ca lcitriol. Outcomes: Fracture and loss of bone mineral density in osteo porosis; increased bone mass, prevention of fractures and improved qua lity of life associated with vitamin D therapies. Evidence: Relevant l aboratory and clinical studies and reports were examined. Greatest rel iance was placed on recent large-scale, randomized, controlled trials; others were noted and their methods critiqued. Clinical practice in J apan was also considered. Values: Reducing fractures, increasing bone mineral density and minimizing side effects of treatment were given a high value. Benefits, harms and costs: Vitamin D maintains the dynamic nature of bone and so presumably helps to keep it healthy. Calcitriol and 1 alpha-OH-D-3 may be effective in increasing bone mass and preve nting fractures in osteoporosis. Calcitriol may be an alternative trea tment in the prevention and management of corticosteroid-induced osteo porosis. Possible side effects of vitamin D analogs and metabolites ar e hypercalcemia, hypercalciuria, renal calcification and renal stones. Recommendations: The use of 1 alpha-OH-D-3 for the treatment of osteo porosis in Canada cannot be supported without larger and longer random ized, controlled clinical trials. Calcitriol appears to prevent verteb ral fractures in patients with osteoporosis. More information is neede d on its mechanism of action and efficacy in preventing hip fractures. Future studies should focus on comparisons with other effective thera pies and on determining whether its effect on fractures is greater tha n that achieved through improved vitamin D nutrition. Patients taking calcitriol at dose levels required for antifracture effects should be monitored for serum and urine calcium response to the drug. Calcitriol should not be given to patients whose calcium intake is at current ge nerally recommended levels. At present, prescription of calcitriol for the treatment of osteoporosis should be reserved for physicians with a special interest in the treatment of metabolic bone disease. Validat ion: These recommendations were developed by the Scientific Advisory B oard of the Osteoporosis Society of Canada at its 1995 Consensus Confe rence. Sponsors: Sponsors of the 1995 conference included the Dairy Fa rmers of Canada, Eli Lilly Canada, Inc., Hoffmann-La Roche Canada Limi ted, Merck Frosst Canada Inc. and Proctor & Gamble Pharmaceuticals Can ada Inc.