Endocrine Abstracts

Context: Denosumab, a fully human monoclonal antibody that inactivates receptor activator of nuclear factor k-B ligand (RANKL), is used for osteoporosis treatment because of its potent anti-resorptive properties. Due to its reversible mode of action, bone resorption increases rapidly after its discontinuation and is accompanied by a quick loss of bone mineral density. Spontaneous vertebral fractures at this period have been recognized as secondary to the rebound of bone resorption. Three cases of rebound-linked hypercalcemia have also been described, one of moderate hypercalcemia following denosumab discontinuation given for osteoporosis, and 2 cases of malignant hypercalcemia in children receiving oncologic doses of denosumab.

Case report: We report the case of an osteoporotic 86-year-old woman treated with denosumab 60 mg subcutaneously every 6 months from 2013 to October 2016 (last injection). She is also known for a primary hyperparathyroidism (PTH 24.2 pmol/l, NV 1.3-9.3), with serum corrected calcium (CCa) at 2.82 mmol/l (NV 2.15-2.5) in April 2017, at the end of denosumab efficacy. Treatment by 30 mg/day cinacalcet lowers CCa to 2.51 mmol/l one month after. In July 2017, she is hospitalized due to weight loss (5 kg,15% body weight), malnutrition and bad health status. Clinical evaluation concludes to malignant hypercalcemia (CaC 3.53 mmol/l) despite lower PTH (10 pmol/l). Initial treatment by hydration and intranasal calcitonin only partially corrects CCa to 2.95 mmol/l. Very high values of bone resorption markers (B-crosslaps 1777 ng/l, NV <573; creatinine 97 umol/l) suggest a rebound effect due to denosumab discontinuation. An X-ray shows new multiple vertebral fractures. After injection of 60 mg denosumab, CCa rapidly lowers to 2.63 mmol/l, and bone resorption markers dramatically decrease (122 ng/l B-crosslaps).

Conclusion: This critical case suggests that hypercalcemia is an underappreciated side effect of denosumab discontinuation, which can become a severe complication when other causes of hypercalcemia, like primary hyperparathyroidism, are present.

Keywords: Bone turnover markers. Denosumab discontinuation. Hypercalcemia. Osteoporosis.