Current and Emerging Therapies for Pediatric Bone Diseases

Most pediatric bone diseases result either from mutations of the essential genes for bone development or from abnormalities of mineral homeostasis. With an increase in non-invasive techniques to measure bone mineral density, the number of children with apparent low bone mineral density is rising. Furthermore, a new classification system proposed by the International Society for Clinical Densitometry now considers osteoporosis a valid diagnosis in children. Osteoporosis is a particular problem among children with conditions such as muscular dystrophy, immobilization, and chronic liver diseases and those who received a prolonged course of glucocorticoids. Pharmacologic agents for treatment of osteoporosis were developed primarily to prevent fragility fractures in postmenopausal women, and studies of their efficacy and safety in children are limited. Recent advances have seen new therapies for bone diseases in children; some of these conditions were deemed incurable in the past. This article reviews data regarding mechanism of action, safety, and efficacy of four bone drugs in pediatric patients. These are (1) zoledronic acid, a long-acting bisphosphonate; (2) denosumab, a RANKL inhibitor; (3) asfotase alfa, a synthetic alkaline phosphatase; and (4) burosumab, a monoclonal antibody against FGF23.