SAT-LB052 Intravenous Bisphosphonate Therapy in Children with Spinal Muscular Atrophy

Abstract

Introduction: Children with Spinal Muscular Atrophy (SMA) are at high risk for poor bone health with 50% of the most severely affected patients reporting at least one fragility fracture prior to age 10 years. Intravenous bisphosphonate (IV BP) has been used for treatment of disuse osteoporosis, primarily in children with cerebral palsy or muscular dystrophy. Our group has previously demonstrated that children with secondary osteoporosis are at increased risk for developing acute adverse events following IV BP but the safety and efficacy of IV BP in SMA population have not been studied. Objective: To evaluate safety profile and the efficacy of IV BP for treatment of concerns for osteoporosis in children with SMA. Methods: We retrospectively reviewed IV BP use in children with SMA at a tertiary pediatric center from 2010 to 2018. Demographic data, fractures history, laboratory indices, and bone mineral density (BMD) by DXA were obtained from electronic medical record and are presented in this case series. Results: Eight children (50% female; 75% SMA type I, 25% SMA type II) were included in this study. The median age of first IV BP infusion was 6.7 years (range 2.3 - 19.0 years). Six had long bone fractures (total of 15) prior to IV BP treatment; two of these fractures were healing fractures discovered 1 month after IV BP started. Two patients were treated based on declining BMD. Patients received a total of 39 infusions (54% pamidronate, 46% zoledronic acid). All received their first IV BP in an inpatient setting due to need for monitoring of respiratory support (BiPAP). Acute phase reactions occurred following 38% (3/8) and 3% (1/31) of initial and subsequent infusions, respectively. All were considered mild and no adverse respiratory events were noted. Hypocalcemia was observed following 5% of infusions (2/37). Hypophosphatemia was common (73%, 27/37) but rarely required intravenous replacement. There was no significant change in BMD at 1 year pre- and post-IV BP treatment among four who had DXA scans for comparison. In 32.7 patient years of follow up, two patients (25%) had total of 3 subsequent fractures, including an occurrence of atypical femur fracture which was observed in one patient 3 years after initiation of IV BP. Conclusion: Although the acute adverse events from IV BP therapy were generally mild, caution needs to be taken given the occurrence of an atypical femur fracture in this population. More follow up is needed to determine the efficacy of therapy in maintaining BMD and preventing further fracture in patients with disuse osteoporosis secondary to SMA. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.