Case Report: Balancing atypical femoral fracture healing and bone metastasis control

Abstrakt

Background Bone-modifying agents (BMAs) represent standard supportive therapy for patients with bone metastases to mitigate skeletal-related events (SREs). Alongside improved cancer survival, cumulative antiresorptive exposure renders atypical femoral fracture (AFF) an important yet infrequent complication. For patients with active metastatic disease, clinical management poses unique challenges, since discontinuation of antiresorptive agents may elevate skeletal-related risk while sustained suppression may impede fracture healing. Case presentation A 56-year-old postmenopausal woman with metastatic breast cancer had received zoledronic acid (4 mg intravenously every 3 months) for 4 years. Because of progression of bone metastases and chest/back pain, treatment was changed to denosumab (120 mg monthly). After three doses, she developed bilateral thigh pain after a minor torsion injury, and radiographs demonstrated bilateral transverse femoral shaft fractures with lateral cortical thickening. Bilateral antegrade intramedullary nailing was performed. Intraoperative bone marrow pathology showed no tumor infiltration. Denosumab was discontinued. Two months later, because of persistent severe osteoporosis and increased bone resorption (β-CTX 0.65 ng/mL), zoledronic acid 4 mg every 12 weeks was restarted. Outcome Eight months after fixation, both fractures achieved radiographic healing with callus formation; no new skeletal-related events were documented during follow-up. Serum β-CTX decreased to 0.35 ng/mL. This clinical course suggests that de-escalated zoledronic acid therapy was temporally associated with fracture healing while sustaining continuous antiresorptive effects in this individual patient. Conclusion This case underscores the diagnostic necessity of distinguishing AFF from metastatic pathological fracture, as well as the therapeutic trade-off between fracture healing and sustained skeletal protection. Sequential antiresorptive exposure, notably prolonged bisphosphonate administration followed by denosumab, warrants vigilant clinical screening for potential AFF. Post-denosumab therapeutic strategies should take rebound bone turnover into consideration. The proposed risk-stratified surveillance framework is evidence-informed but remains unvalidated and should not be interpreted as formal clinical guidance.