MON-814 Rebound Hypercalcemia Months After Denosumab Administration

Abstract Disclosure: S. Reyes: None. A. Samat: None. Introduction:Denosumab is an antiresorptive agent used for the treatment of osteoporosis. It has the risk of hypercalcemia after 3 months of discontinuation, however, it is estimated that this is infrequent or overlooked due to lack of symptoms (1). We present a case of a patient who was found to have symptomatic hypercalcemia 6 months following denosumab. Clinical Case: A 79 year old female with a history of CKD IV, myelodysplastic syndrome, intermittent hypo- and hypercalcemia, osteoporosis on denosumab since 2013, and dementia who presented to the hospital after a fall and worsening mental status was found to have hypercalcemia. Prior to admission serum calcium was 10.5-12.3 mg/dL. At presentation, calcium was 11.3 mg/dL, phosphorus 6 mg/dL, magnesium 2.5 mg/dL and PTH 14 pg/mL. She received her last dose of denosumab 6 months prior. Her calcium and vitamin D supplementations were discontinued 1 year ago when she had a similar presentation. During that admission a full work-up of non-PTH dependent hypercalcemia was carried out and she had negative SPEP and immunofixation, low calcidiol and calcitriol levels, a normal PTHrP, and a negative CT imaging showing no evidence of granulomatous or metastatic disease. During this admission again secondary work up for non-PTH dependent hypercalcemia was negative. During this admission she received IVF, three doses of 240 units of calcitonin initially, and on day 3 of admission 60mg denosumab. On day 5, she had an appropriate decrease in calcium level to 10.5mg/dL with her mental status closer to her baseline and she was discharged. She was prescribed a daily multivitamin and vitamin D. Two weeks post-discharge, calcium levels continued to decrease with the most recent level 6.8 mg/dL. Conclusion: Denosumab is a monoclonal antibody that essentially inhibits osteoclast activity. This leads to decreased bone resorption and a reduction in calcium mobilization into the circulation (2). Rebound hypercalcemia after the discontinuation of denosumab is an infrequent effect that is due to the high bone turn over that occurs in the period without treatment. It is important to rule out other pathologies that may explain the hypercalcemia, however, in our patient no other etiologies were found. Additionally, two episodes approximately 6-7 months after her last dose and normalizing or becoming hypocalcemic soon after is supporting our hypothesis. This case highlights the hypercalcemic effect of denosumab if not continued as scheduled and the potential hypocalcemic effect after its administration. References:(1) Horiuchi, K., Kobayashi, E., Mizuno, T., Susa, M., & Chiba, K. (2021). Hypercalcemia following discontinuation of denosumab therapy: A systematic review. Bone Reports, 15, 101148.(2) Kim, D. (2022). Hypocalcemia after the administration of denosumab in a patient with osteoporotic fracture and vitamin D deficiency. J Endocrinol Metab, 12(3), 111-115. Presentation: Monday, July 14, 2025