Contrasting PTH Response of Denosumab Use in Dialysis Patients: A Report of 2 Cases

Abstract

A common complication of end-stage renal disease (ESRD) is mineral and bone disorder. Yet, many anti-osteoporotic drugs are contraindicated in ESRD patients. Denosumab, a monoclonal antibody, does not require renal dose adjustment. However, its use is uncertain due to a lack of safety and efficacy of data in this population. Two hemodialysis patient cases of contrasting responses in parathyroid hormone (PTH) after denosumab administration were observed. Patient 1, a 62-years-old male received denosumab 60 mg at Day 0. His calcium decreased from 8.8 mg/dL to 6.8 mg/dL on Day 30. The PTH level increased from 265 pg/mL to 372 pg/mL after 30 days. Calcium and PTH levels approached normal range after increasing doses of vitamin D/calcium supplements, and calcitriol. Patient 2, a 72-years-old male on hemodialysis also received denosumab 60 mg on Day 0. His baseline calcium and PTH were 9.2 mg/dL and 420 pg/mL, respectively. On Day 30, his calcium level decreased (6.8 mg/dL) but, PTH level drastically increased (>5000 pg/mL). Denosumab commonly causes hypocalcemia and hyperparathyroidism since it inhibits osteoclast activation, reduces calcium release from bone and increases PTH levels as a compensatory mechanism. With a wait-and-watch approach, Patient 2’s levels approached the normal range (calcium 9.6 mg/dL and PTH 274 pg/mL at Day 90).

Effect of Denosumab on Bone Health, Vascular Calcification, and Health-Related Quality of Life in Hemodialysis Patients with Osteoporosis: A Prospective Observational Study

“…Despite efforts to mitigate hypocalcemia [ 3 , 17 ], the significant increase in PTH post-denosumab administration in our study suggests that mechanisms beyond hypocalcemia triggered this increase. As a mechanism to explain this, the possibility of an osteoanabolic effect of PTH due to a decrease in cortical porosity in the early stages of denosumab administration has been suggested [ 27 , 28 ], but the exact mechanism is not yet known.…”