SAT-509 Denosumab Use in Tertiary Hiperparathyroidism with Fracture

Abstract

A 24 year old woman with a chronic kidney disease of unknown etiology on hemodialysis with tertiary hyperparathyroidism, PTH of 3368 pg/ml (NV: 8-51 ) comes into the emergency room. She had fractures of both femurs after a fall in the bathroom. She underwent parathyroiddectomy leaving 50mg of the left superior parathyroid. The pathology ruled out carcinoma. She received treatment with densoumab taking into consideration her previous PTH, kidney function and fractures. She was later taken to orthopedic surgery on her right femur without being able to do a fixation of the fracture. The calcium dose was increased due to mild hypoclacemia. On the last day a ionic calcium was normal after 20 days. The patient went home taking 1200mg of calcium gluconate tid and 0.5mcg of calcitriol bid. Denosumab is a full length human monoclonal antibody binding to the receptor activator of nuclear factor kappa-B ligand (RANKL), it decreases the signal that is essential for osteoclasts formation, maturation, function and survival. The use in CKD is based on elimination mediated by the reticuloendothelial system and receptor mediated endocytosis. Hypocalemia has to be considered as an adverse effect. 1 Parathyroidectomy reported an increase in 10% of bone mass after a year after in CKD and secondary hyperparathyroidism. In the study of Dr. Chen, the patients with a PTH higher than 1000pg/mL were candidates to surgery however, those patients had high risks of cardiovascular mortality and they received denosumab. After 6 months of treatment the femoral neck BMD increased 23.7% and lumbar spine 17.1% which is almost double of the value after parathyroidectomy. Dr. Chen states “⋯ use denosumab in dialysis patients to treat high bone turnover hyperaparathyroidism because PTH concurrently stimulates RANKL expression and inhibits OPG by osteoblasts and thus promotes osteoclastogenesis”2. Hypocalcemia is the most adverse effect described in this context. The estimated incidence of hypocalcemia was 42% and it occurred 7 to 20 days after the first dose and reached nadir of low calcium levels in the first two weeks up to two months. However there have been some reports that state that the use of calcium and calcitriol prior to the use of the medication could decrease the rate of hypocalcemia. 3. Bibliography Manandhar, S; Selk, K; Sobel, S. Denosumab use for severe hypercalcemia in a man iwth end stage renal disease on hemodialysis. AACE clinical case reports (3); 2017;3:e116-e120. Chen, C; Chen, N; Hsu, C; et all. An open label, prospective pilot clinical study of denosumab for severe hyperparathyroidism in patients with low bone mass undergoing dialysis. J Clin Endocrinol Metab, 2014:99(7):2426-2432. Thongprayoon, C; Acharya, P; Acharya, C; et all. Hypocalcemia and bone mineral density changes following denosumab treatment in end stage renal disease patients: a meta analysis of observational studies. Osteoporosis Int. 2018.