Abstract: TH-PO174
Denosumab-Induced Severe Hypocalcemia and Hyperparathyroidism in a Peritoneal Dialysis Patient
Session Information
- Drug Events Trainee Case Reports
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Akinjero, Akintunde M., Stony Brook University Medical Center, Stony Brook, New York, United States
- Estrada, Chelsea C., Stony Brook University Medical Center, Stony Brook, New York, United States
- Suh, Heesuck, Stony Brook University Medical Center, Stony Brook, New York, United States
Introduction
Denosumab is increasingly used in the treatment of osteoporosis in patients with End Stage Renal Disease (ESRD). The safety of Denosumab in ESRD is unproven. We report a case of severe hypocalcemia and hyperparathyroidism after Denosumab use in ESRD.
Case Description
A 56-year-old woman with history of osteoporosis, secondary hyperparathyroidism and ESRD on peritoneal dialysis for the past eight years, presented to clinic with complaint of paresthesias of hands and feet for two weeks. Vital signs and physical exam were unremarkable. Laboratory work-up showed profound hypocalcemia (corrected calcium of 6.8 mg/dL) and markedly high intact PTH (iPTH) of 3448 pg/mL (Table 1), with normal phosphate (5.1 mg/dl) and alkaline phosphatase (193 U/L). Upon medication review, she notably received denosumab 60 mg subcutaneously for the first time, two weeks prior to her visit.
Before the use of denosumab; calcium, phosphorus, and 25-vitamin D were normal, with mildly high iPTH (Table 1). We gave total daily doses of 3,000 mg oral calcium and 4,000 mg Renvela. With these drugs, her symptoms resolved with normalization of serum calcium six weeks later, and iPTH ten weeks later (Table 1). She was later closely monitored in clinic.
Discussion
Denosumab is a monoclonal antibody used to treat osteoporosis; it binds to receptor activator of nuclear factor-kappa B ligand, an osteoclast differentiating factor, to inhibit bone resorption and increase bone mineral density. Bisphosphonates are first line treatment for osteoporosis. However, bisphosphonates are contraindicated in ESRD due to impaired clearance. Denosumab is not renally cleared, hence seen as an alternative for treating osteoporosis in ESRD.
Decreased phosphate clearance, reduced production of 1α hydroxylase, and elevated fibroblast growth factor-23 all predispose ESRD patients to hypocalcemia. Denosumab further increases this risk by downregulating osteoclast activity.
Denosumab continues to be used in ESRD, with increasing reports of hypocalcemia. Our case outlines the life-threatening hypocalcemia that may occur, and highlight the need for closer monitoring in ESRD patients receiving denosumab.
Table 1. Changes in Calcium and iPTH levels after Denosumab.
Before Denosumab | 2 weeks after Denosumab | 6 weeks after Denosumab | 10 weeks after Denosumab | |
Corrected Calcium | 9.7 | 6.8 | 8.7 | 10.6 |
iPTH | 584 | 3448 | 3526 | 399 |