SAT-768 - Bone Turnover Markers Can Redirect Management of PTHrP Mediated Hypercalcemia: Recurrent Hypercalcemia with Normal Resorption Markers.

Introduction: Hypercalcemia of malignancy is frequently treated with IV bisphosphonates, but response varies based on the dominant mechanism; osteoclast-mediated bone resorption vs. non skeletal action of PTH-related peptide (PTHrP). Bone resorption markers (serum CTx) may help identify when additional antiresorptive therapy is likely to provide incremental benefits with recurrent hypercalcemia. Control of underlying cancer is more likely to prevent recurrent hypercalcemia.

Case Report: A 70-year-old woman with a medical history significant for squamous non-small cell lung cancer with brain metastases on chemo/immunotherapy and radiation therapy, paraneoplastic hypercalcemia, and low trauma rib fractures was referred for endocrine evaluation of osteoporosis and recurrent hypercalcemia. Bone density done in the past showed osteoporosis (lumbar spine T-score -2.7, total hip -2.9, femoral neck -3.2). Initial evaluation during severe hypercalcemia (14.1 mg/dL) showed suppressed PTH (12) with markedly elevated PTHrP (91), consistent with humoral hypercalcemia of malignancy. High serum CTx (1796) indicated markedly elevated bone resorption. IV fluids and Zoledronic acid (ZA) infusion normalized calcium for 6 weeks. Recurrent hypercalcemia was treated with monthly ZA dosing through January 2025, though serum calcium normalized after 2 cycles of Pembrolizumab + Carboplatin + NAB - Paclitaxel. Maintenance Pembrolizumab was continued after 4 cycles of chemotherapy. In June 2025 mild hypercalcemia Ca 11.3 mg/dl recurred despite normal bone turnover CTX 253 and PTHrP of 22. Chemotherapy was changed to Ramucirumab + Docetaxel. CTx remained suppressed at 176 in 1/2026, 6 months after a single additional dose of Zolendronic acid. Low PTHrP of 8 suggests control of tumor activity. No recurrence of hypercalcemia.

Discussion: Despite evidence of strong bisphosphonate effect (CTx suppression), hypercalcemia recurred when PTHrP remained elevated, suggesting limited benefit from repeat antiresorptive dosing once bone turnover is suppressed. In this case, CTx helped distinguish between bone resorption driven vs. predominantly non skeletal effect of PTHrP and supported holding additional zoledronic acid when CTX remained low ( < 350) and calcium was normal, shifting management toward tumor control.

Conclusion: This case demonstrates a calcium-CTx disconnect, where serial CTx helped avoid repeat IV bisphosphonate exposure after bone turnover was already suppressed. Bone turnover markers along with PTHrP levels may serve as an adjunct for decision making in recurrent PTHrP-mediated hypercalcemia.

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