Bone Abstracts

Intravenous (IV) bisphosphonates (pamidronate, zoledronic acid and neridronate) are the mainstays of medical therapy for numerous pediatric bone diseases. While most frequently prescribed for hypercalcemic disorders and osteoporosis, their potent analgesic effects have also led to their use in fibrous dysplasia, osteonecrosis, sickle cell disease, chronic non-bacterial osteomyelitis, and complex regional pain syndrome. Bisphosphonates given IV are highly effective in preventing incident vertebral fractures in most at-risk patients; their efficacy in stabilizing vertebral dimensions may be attenuated in children with aggressive risk factors and advanced vertebral collapse, highlighting the importance of early vertebral fracture detection. The incidence of long bone fractures is reduced by about 50% in bisphosphonate-treated osteogenesis imperfecta (OI). The lack of a more dramatic fall in incident long bone fractures reflects factors other than cell metabolism in OI, including small bone diameter, limb deformity and that cortical density is less amenable than trabecular density to positive increases. Despite their convenient administration, oral bisphosphonates have shown insufficient efficacy in controlled trials to justify their use first-line in children with osteoporosis; their role as maintenance therapy remains controversial due to lack of sufficient evidence. First-infusion side effects and the burden of IV therapy have opened the door to new approaches. RANKL-targeted denosumab, administered intermittently by sub-cutaneous injection, has received health authority approvals for adult osteoporosis; international pediatric trials in OI and glucocorticoid-induced osteoporosis are underway. In contrast to bisphosphonates, denosumab is short-acting with potential for rebound from osteoclast inhibition, manifesting as reactivation of skeletal resorption, bone density loss and frank hypercalcemia, all of which respond to bisphosphonate therapy. The frequency and extent of the rebound phenomenon in different pediatric settings, along with optimal dosing and frequency of both bisphosphonates and denosumab to achieve clinical endpoints while avoiding over-treatment, merit ongoing study.

Disclosure: Consultant to and participating in clinical trials with Novartis and Amgen.

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