Treatment of congenital osteopetrosis in the rabbit with high-dose 1,25-dihydroxyvitamin D.

摘要: Osteopetrosis is a congenital metabolic bone disease characterized by skeletal sclerosis resulting from defective osteoclast-mediated resorption. has been described in several animal species (mouse, rat, and rabbit) children. Bone marrow transplantation, originally shown to reverse the some mutations, effective curing osteopetrosis Unfortunately, not all children with are candidates for or respond transplantation. Recent studies have that mutations inheriting significantly elevated serum levels of 1,25-(OH)2D. Based on possibility there may be resistance 1,25-(OH)2D, high-dose calcitriol therapy used treat stimulated parameters In this study, we examined effects various osteopetrotic rabbit. Mutant rabbits normal littermates were given continuous infusions via subcutaneously implanted osmotic minipumps 2 weeks at dose 0.5, 2.5, 25 micrograms/kg/per day. Untreated mutant hypocalcemic hypophosphatemic presence 1,25-(OH)2 comparison their littermates. Calcitriol resulted dose-dependent increases circulating 1,25-(OH)2D both rabbits. However, evaluation other response demonstrated significant differences between At highest dose, animals rapidly became hypercalcemic osteoporotic, accompanied weight loss failure thrive; mutants remained but did exhibit deleterious physical seen treated Although number osteoclasts increased normals, osteoclast phenotype former abnormal. These data indicate although very high achieved mutants, activation resorption subsequent improvement was observed.