PSAT197 Treatment of Paget's Disease of the Skull With Denosumab: A Case Report

BACKGROUND: Paget's disease of bone (PDB) is a common skeletal disorder characterized by increased osteoclastic activity and bone resorption followed by increased osteoblastic bone formation leading to an abnormality in modeling and remodeling of bone. Bisphosphonates are the most common treatments for PDB, with zoledronic acid being the most effective medication, but treatment would be difficult if bisphosphonates are contraindicated. Clinical case: We report a case of PDB of the skull in a 75-year-old woman presenting with a persistent headache that was successfully treated with denosumab. The patient had been complaining of severe headaches since December 2020. Her skull x-ray and laboratory results [calcium 8.2 mg/dL (range: 8.5-10.5 mg/dL), albumin 4 g/dL (range: 3.4- 4.8 g/dL), alkaline phosphatase 132 U/L (range: 35-104 U/L)] were consistent with PDB. Brain MRI and bone scintigraphy also showed skull changes consistent with PDB. Importantly, a DXA scan from July 2020 showed osteopenia, and her primary care provider treated it with denosumab in the first week of December 2020. At the time of PDB diagnosis in January 2021, zoledronic acid could not be administered because of mild hypocalcemia that was corrected with calcium carbonate. However, the headaches resolved, alkaline phosphatase normalized, and zoledronic acid was put on hold. Up until January 2022, she remains asymptomatic and alkaline phosphatase remains normal. CONCLUSION: This case illustrates the successful management of PDB of the skull with denosumab, a human monoclonal antibody against RANKL. To the best of our knowledge, there have not been reported cases of full recovery of PBD with denosumab. Although PBD pathophysiology remains poorly understood, this case suggests that increased RANKL activity might mediate PBD directly or indirectly. Thereby, denosumab might be an effective treatment for some cases of PDB. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.