Optimizing Vitamin D and calcium intake as well as a weight bearing exercise program are central approaches in the prevention and treatment of osteoporosis. Despite increased awareness of this disorder in the pediatric population and more active implementation of these principles, an ever increasing number of children with osteoporosis present with symptomatic disease; that is progress to the stage of frequent peripheral fractures, vertebral compression fracture and/or deliberating pain. Bisphosphonates are often then added to the therapeutic regiment. However, it is widely acknowledged that little is currently known about the key factors that might predict the safe and effective use of these agents in this population.