PSAT189 Severe Hypocalcemia and Hypophosphatemia Associated with Denosumab use in a Chronic Myeloid Leukemia Patient on Imatinib

Abstract

Background Hypocalcemia and hypophosphatemia are known side effects of Denosumab, especially in presence of risk factors including underlying chronic kidney disease, osteoblastic metastasis, high bone turnover states, vitamin D deficiency and preexisting hypocalcemia. We report a unique case of prolonged severe hypocalcemia and hypophosphatemia in a patient with CML on Imatinib, treated with Denosumab for osteoporosis. Clinical case A 73-year-old lady with history of CML, on Imatinib for 4 years and osteoporosis with a chronic L1 compression fracture treated with her second dose of Denosumab 3-months back, presented with complaints of numbness and tingling involving the entire body. Labs revealed severe hypocalcemia (calcium 5.6 mg/dL, ionized calcium 2.93 mg/dL), severe hypophosphatemia, (phosphorus of 0.5mg/dL) and a low normal magnesium level of 1.5mg/dL, with normal ALP, liver and kidney function parameters. Of note she had normal calcium, phosphorus and vitamin D levels before receiving denosumab. Further work-up revealed an elevated PTH level of 241 pg/mL, normal 25 hydroxy vitamin D level of 26.0 ng/ml, slightly low 1,25 (OH) vitamin D of 16pg/ml and an elevated FGF 23 of 299RU/mL (normal <180RU/mL). Her calcium and phosphorus levels remained suboptimal despite treatment with up to 24 grams of calcium carbonate supplementation daily, K-phos 1 packet QID and calcitriol 0.25 mcg TID. 24-hour urine calcium and phosphorus levels were low at 4mg/day and 0.2mg/day respectively. Fractional excretion of phosphate was 13.63%, suggesting renal phosphorus wasting, likely from an elevated FGF23. Bone scan showed no metastatic lesion. After discussion with oncology, Imatinib was held inpatient and she was started on intravenous calcium gluconate infusion, and continued on Calcitriol, vitamin D3 and K-phos supplementation. After receiving almost 18gm of calcium gluconate intravenously over 2 days, her hypocalcemia and hypophosphatemia resolved with improvement in symptoms. Conclusion Hypocalcemia is a recognized adverse effect of Denosumab that is seen in patients with underlying risk factors. Emerging data now suggests the deregulatory effect of long term Imatinib therapy on bone formation by inhibition of osteoclastic activity along with transient increase in osteoblastic activity leading to retention and sequestration of calcium and phosphate in bone, resulting in hypocalcemia and hypophosphatemia. Ours is the first reported case of severe hypocalcemia and hypophosphatemia observed in a CML patient on Imatinib after receiving Denosumab, with resistance to high dose oral calcium and phosphate supplementation, requiring intravenous supplementation and transient discontinuation Imatinib. The elevated FGF 23 likely played a key role in severe hypophosphatemia. This unique case addresses the prospect of occurrence of severe hypocalcemia and hypophosphatemia in patients on Imatinib receiving Denosumab, while questioning the possibility of potentiation of the osteoclast inhibitory effect of this medication when used in patients on long term Imatinib therapy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.