Severe Hypocalcemia and Dramatic Increase in Parathyroid Hormone after Denosumab in a Dialysis Patient: A Case Report and Review of the Literature

Abstract

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is frequently present in advanced stages of chronic kidney disease (CKD) patients with high risk of fracture and elevated socioeconomic burden. Denosumab, an injectable human monoclonal antibody with affinity for nuclear factor-kappa ligand (RANKL), is an effective treatment for osteoporosis in postmenopausal women and men. Unlike the bisphosphonates, the pharmacokinetics and pharmacodynamics of denosumab are not influenced by the renal function and are being increasingly used for patients having CKD-MBD with low bone mineral density (BMD) to reduce the risk of fragility fractures. Hypocalcemia is a known side effect of this drug along with compensatory increase in parathyroid hormone (PTH). However, limited information is available in the literature regarding this potentially life-threatening side effect with denosumab in end-stage renal disease (ESRD) patients on dialysis. We present a patient with ESRD on peritoneal dialysis who developed severe symptomatic hypocalcemia and dramatic increase in PTH following denosumab therapy. She was conservatively managed with calcium supplementation and appropriate adjustment in calcium dialysate. We have also reviewed the literature on the use of denosumab in dialysis patients and looked at additional factors that may precipitate severe hypocalcemia in these patients. We believe that denosumab should be used with caution in dialysis patients since it may lead to profound hypocalcemia. Clinicians should ensure special attention in recognizing patients at risk of developing this serious adverse effect, so that prompt treatment and preventive strategies can be implemented.

Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review

“…Denosumab treatment should not be discontinued post KT because discontinuation of the treatment would lead to an increased risk of vertebral fractures and rapid loss of BMD [ 150 ]. Close monitoring and supplement of calcium and calcitriol preemptively before starting denosumab are needed to avoid the side effect of hypocalcemia [ 151 , 152 , 153 ]. In addition, CKD G4–5 and male sex were found to be associated with denosumab-induced hypocalcemia [ 154 ].…”

Hypocalcemia After the Administration of Denosumab in a Patient With Osteoporotic Fracture and Vitamin D Deficiency

“…Denosumab inhibits osteoclastic bone resorption, leading to hypocalcemia by reducing calcium mobilization from the bone into the bloodstream, and denosumab is more potent than zoledronic acid [8,13]. The risk factors for denosumabassociated hypocalcemia include bone metastatic cancer, renal impairment, vitamin D deficiency, the lack of prophylactic supplementation of calcium and/or vitamin D, preexisting hypoparathyroidism, hypomagnesemia, and high bone turnover state as assessed by turnover markers [2,4,[7][8][9][16][17][18]. Additionally, concomitant use of medications that increase calcium loss or potentiate the effect of denosumab (e.g., glucocorticoids, some anticonvulsants, bisphosphonates, and calcimimetics) increases the risk of hypocalcemia [4,17].…”

Denosumab-Induced Hypocalcemia after Billroth II Gastric Bypass Surgery

“…e risk of hypocalcemia following denosumab use for osteoporosis has been demonstrated in multiple case reports and case series for patients with chronic kidney disease [7][8][9][10] and in individual case reports for patients with primary sclerosing cholangitis [11], Crohn's disease [8,12,13], and a history of sleeve gastrectomy for marginal gastric ulcers [12]. A few cases of hypocalcemia with denosumab have been reported in patients with a history of bariatric surgery, but each of these was likely secondary to vitamin D deficiency [14,15].…”