MON-808 Multiple Vertebral Fractures After A Single Dose Of Denosumab

Abstract Disclosure: J.L. Ryan: None. L.S. Eldeiry: None. Background: Denosumab, a human monoclonal antibody inhibitor of RANKL(Receptor Activator of Nuclear Factor-kappa B Ligand), inhibits osteoclast activity and bone resorption, thereby serving as an effective treatment for osteoporosis and hypercalcemia. Denosumab is well known for a rebound phenomenon after discontinuation, whereby the absence of subsequent therapy leads to increased bone resorption, loss of bone density and risk of multiple vertebral fractures. This effect has been reported to occur after several doses, as soon as 7 months after the last injection, in ∼7% of patients who discontinue it without subsequent therapy1. We present a case of rebound fractures occurring in a patient who received one dose of denosumab. Clinical Case:In May 2024, a 60-year-old female with a history of mild, intermittent hypercalcemia, nephrolithiasis and normal renal function presented to the ER after 10 days of nausea and vomiting. Laboratory studies showed a serum calcium of 16 mg/dL (8.7-10.7 mg/dL) and creatinine 3.63 mg/dL (0.6-1.1 mg/dL). She was treated with IV fluids, calcitonin and one dose of denosumab 60 mg. She then developed severe hypocalcemia (serum calcium 6.9 mg/dL) treated with high dose calcium carbonate and calcitriol. Extensive workup of hypercalcemia was unrevealing and ultimately attributed to severe dehydration superimposed on mild underlying primary hyperparathyroidism. Post-discharge, hypocalcemia resolved and renal function normalized off calcium and calcitriol. Twenty-four hour urine calcium excretion was normal. In December 2024, she presented to the hospital with severe, atraumatic back pain. MRI confirmed 5 spontaneous vertebral fractures (T12,L1,L3-5). DXA showed osteoporosis, with the lowest T score at the femoral neck of -3.4. She was treated with zoledronic acid infusion and scheduled for kyphoplasty due to intractable pain. Conclusion: Longer duration of denosumab therapy is a known risk factor for rebound fractures, but to our knowledge, this phenomenon has not been reported after a single dose1. Our patient experienced 5 vertebral fractures 7 months after a single dose of denosumab administered for hypercalcemia. Although osteoporosis and mild hyperparathyroidism may have contributed to her bone fragility, the clinical presentation is most consistent with rebound fractures after denosumab discontinuation. This case illustrates the importance of planning follow up therapy for patients who discontinue this medication, even after one injection. 1. Jain S. Prevention and Management of Denosumab Discontinuation Rebound Fractures. Endocrinol Metab Clin North Am. 2024 Dec;53(4):559-583. Presentation: Monday, July 14, 2025