Bisphosphonate-Related Pathological Femoral Fracture in a Child with ACTG2-Related Intestinal Failure and Metabolic Bone Disease: A Case Report.

Introduction: Atypical femoral fractures (AFFs) are stress-type insufficiency fractures classically associated with long-term bisphosphonate therapy in adults. Reports of AFFs in pediatric patients are limited primarily to osteogenesis imperfecta or other monogenic bone disorders following prolonged exposure. We report the first case of an AFF occurring after zoledronic acid administration in a child with ACTG2 gene mutation-related intestinal failure and severe metabolic bone disease. Case Report: An 8-year-old male with ACTG2-related intestinal failure, total parenteral nutrition dependence, and multiple fragility fractures presented following initiation of annual zoledronic acid therapy. He had previously undergone right femur shaft fracture fixation via flexible intramedullary rods. Approximately 7 months later, he sustained a minimally displaced subtrochanteric proximal femoral fracture fulfilling American Society for Bone and Mineral criteria for AFF: A short oblique orientation, subtrochanteric location, cortical thickening, and minimal trauma mechanism. The fracture required conversion to open reduction and internal fixation with a plate-and-screw construct. Eight-week post-operative radiographs demonstrated progressive fracture healing with advancing periosteal callus formation and maintained hardware alignment. Conclusion: Children with severe metabolic bone disease and underlying smooth muscle gene mutations may be vulnerable to AFF after bisphosphonate exposure. Clinicians initiating bisphosphonate therapy in children with severe metabolic bone disease and pre-existing intramedullary hardware should conduct thorough pre-treatment imaging and maintain vigilance for AFF patterns during follow-up. Level of Evidence: Level V - Expert Opinion/Case Report.