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Cinacalcet/denosumab Rebound effect in the form of hypercalcaemia and spontaneous vertebral fractures: case report

An elderly woman [exact age at the onset of event not stated] developed rebound effect in the form of hypercalcaemia and spontaneous vertebral fractures following discontinuation of denosumab. Additionally, she developed digestive intolerance during treatment with cinacalcet for hyperparathyroidism [not all routes and outcomes stated, duration of treatments to reactions onset not stated]. The woman, who had hypercalcaemia in the context of primary hyperparathyroidism refused the proposed surgical treatment. She had densitometric osteoporosis and had been receiving SC injection of denosumab 60mg every 6 months from 2013 to October 2016 with good but insufficient effect. The treatment with denosumab was discontinued due to an unknown reason. In April 2017, at the end of denosumab efficacy her serum albumin-corrected calcium level was 2.82 mmol/L and serum parathyroid hormone (PTH) level was found to be elevated. Therefore, the treatment with cinacalcet 30mg daily was initiated and after a month calcium level decreased to 2.51 mmol/L, which suggested good control over hypercalcaemia. However, during this treatment, she developed digestive intolerance due to cinacalcet. Her treatment with cinacalcet was lowered first and eventually, discontinued. In mid July 2017, cincalcet was reintroduced after elevation in calcium level to 3.53 mmol/L. At the end of July 2017, she was hospitalised due to weight loss, malnutrition and poor health status. Additionally, she developed anorexia. A clinical evaluation showed severe hypercalcemia with lower PTH 10 pmol/L under cinacalcet. Initial treatment with hydration and intranasal calcitonin partially corrected the calcium level to 2.57 mmol/L. The cinacalcet therapy was given in the context of maintaining low PTH; however, calcium level was found to be elevated again. Laboratory investigations revealed high levels of type I collagen c-terminal telopeptide in spite of mild renal dysfunction significant with acute kidney injury. Based on these findings, a rebound effect due to discontinuation of denosumab was confirmed. Further examination revealed three spontaneous vertebral fractures. Therefore, the treatment with denosumab was restarted, and after a single 60mg injection, serum calcium rapidly decreased to 2.63 mmol/L. Following resumption of denosumab injections, her calcemia became stable between 2.60 and 2.80 mmol/L, with no other treatment. PTH levels increased when calcium levels were close to normal values. On further examination, she was diagnosed with parathyroid adenoma, and she accepted the surgical treatment. She underwent parathyroidectomy and her calcium level became normal in the presence of denosumab therapy. Camponovo C, et al. Hypercalcemia upon denosumab withdrawal in primary hyperparathyroidism: a case report and literature review. Osteoporosis International 31: 2485-2491, No. 12, Dec 2020. Available from: URL: http://doi.org/10.1007/s00198-020-