Recombinant Osteoprotegerin for Juvenile Paget's Disease

Juvenile Paget's disease, a genetic bone disease characterized by accelerated bone turnover, results from inactivating mutations in the gene encoding osteoprotegerin, a key regulator of osteoclastogenesis. The authors investigated the effects of recombinant osteoprotegerin in two adult siblings with juvenile Paget's disease. After 15 months, radial bone mass had increased, skeletal bisphosphonate retention had decreased, and there was radiographic improvement. Osteoprotegerin may be therapeutic in juvenile Paget's disease. The authors investigated the effects of recombinant osteoprotegerin in two adult siblings with juvenile Paget's disease. Osteoprotegerin may be therapeutic in juvenile Paget's disease. The change in the size and shape of the skeleton during growth and its renewal during adult life depend on the closely coordinated activity of bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts). The receptor activator of nuclear factor-κB (RANK) ligand (RANKL)–osteoprotegerin–RANK system constitutes a critical mechanism for signaling between osteoblasts and osteoclasts. 1 In response to factors such as parathyroid hormone that stimulate the remodeling cycle, the cytokine RANKL is expressed and secreted by osteoblasts. The interaction of RANKL with RANK, located on preosteoclasts, stimulates the differentiation of these cells into active, bone-resorbing osteoclasts. In parallel with the production of RANKL, . . .