Preoperative Zoledronate Is Safe for Children With Medical Complexity Undergoing Posterior Spinal Fusion for Neuromuscular Scoliosis

Children with Medical complexity (CMC) and neuromuscular scoliosis (NMS) are prone to bone fragility and secondary osteoporosis due to immobility, chronic illness, nutritional deficiencies, and medication side effects. The resultant osteoporotic bone compounds operative challenges, contributing to complications such as implant failure by fracture, pedicle screw loosening and cut-out, proximal junctional kyphosis and pseudarthrosis. Pre-operative optimization of bone fragility has the potential to further improve surgical outcomes in the CMC population. Despite evidence for the safety and efficacy of zoledronate infusions in paediatric conditions (e.g. osteogenesis imperfecta), its tolerance, safety, and efficacy in medically complex children with neuromuscular scoliosis has not been established. The current investigation aims to establish the safety of pre-operative bisphosphonate therapy in children with CMC and NMS at a pediatric tertiary referral center as part of the implemented pre-operative optimization pathway. A retrospective review was conducted of patients who had undergone pre-operative zoledronate infusions as part of pre-operative optimization at a single tertiary pediatric referral center. The protocol included three infusions with an initial 0.0125mg/kg dose, a 0.0375mg/kg dose at 6 weeks, and 0.05mg/kg dose at 6 months. Surgery was scheduled no sooner than 6 weeks after infusion. Patient demographics, co-morbidities, medications, laboratory investigations, infusion protocol, and adverse events were collected. 47 patients received at least one pre-operative zoledronate infusion. Of these, 66% (31) completed the pre-operative optimization, receiving three infusions of zoledronate. The most common presenting etiology was cerebral palsy (70%), followed by Rett syndrome (9%), and congenital myopathy (9%). 66% of patients were GMFCS level 5 with 26% being GMFCS level 4. Minor adverse events were noted in 6 patients (13%), including 2 episodes of post-infusion hypocalcemia, 2 episodes of self-limited flu-like symptoms, 1 episode of nephrolithiasis and 1 episode of unspecified hypotension which resolved after receiving oral fluids. There were no major adverse events requiring hospital admission or emergency department presentation related to zoledronate infusions. 21 patients have reached 2 years follow up with signs of no clinical pseudarthroses. 1 patient was noted to have a broken pedicle screw at their 6 months follow-up but, to date, has had no further radiographic concerns that could indicate pseudarthrosis. Overall, no major adverse events were noted after pre-operative zoledronate infusions. The minor adverse events noted were self-resolving or resolved with minimal intervention. Zoledronate infusion can safely be included as part of a pre-operative optimization pathway in CMC with NMS. Further research is required to optimize patient selection, infusion dose and schedule, impact on screw pull-out, and long-term complications.