Long-term follow up after denosumab treatment for osteoporosis – rebound associated with hypercalcemia, parathyroid hyperplasia, severe bone mineral density loss, and multiple fractures: a case report

Abstract

Background: The rebound effect after stopping treatment with denosumab may be associated with rapid loss of the gains in bone mineral density achieved with treatment, high levels of bone remodeling markers, the occurrence of vertebral fractures, and even hypercalcemia. Case presentation: A 64-year-old osteoporotic Caucasian woman suffered from a fracture of her second lumbar vertebra in 2004. From January 2005, she was treated with denosumab for 9 years, with good densitometry results for her hip and lumbar areas, and no fractures over the last 6 years of treatment. Ten months after the treatment with denosumab was stopped, a cascade of vertebral fractures, including some in unusual locations (third thoracic vertebra), and multiple rib fractures in a context of hypercalcemia, suggested possible malignancy. A complete evaluation, including systemic, biological, and biopsy analyses, ruled out this hypothesis. The hypercalcemia was associated with normal plasma phosphate and vitamin D concentrations, and a high parathyroid hormone level, with an abnormal fixation of the lower lobe of the thyroid on sesta-methoxy-isobutyl-isonitrile scintigraphy. Histological analysis of the excised parathyroid tissue revealed hyperplasia. The associated thyroidectomy (goiter) led to the discovery of a thyroid papillary microcarcinoma. Conclusions: We consider the consequences of this rebound effect, not only in terms of the major loss of bone density (return to basal values within 3 years) and the multiple disabling fracture episodes, but also in terms of the hypercalcemia observed in association with apparently autonomous tertiary hyperparathyroidism. Several cases of spontaneous reversion have been reported in children, but the intervention in our patient precluded any assessment of the possible natural course. The discovery of an associated thyroid neoplasm appears to be fortuitous. Better understanding of the various presentations of the rebound effect after stopping treatment with denosumab would improve diagnostic management of misleading forms, as in this case. Bisphosphonates could partially prevent this rebound effect.

Denosumab treatment for refractory hypercalcemia in a hemodialysis patient with tertiary hyperparathyroidism

“…Calcium carbonate and alfacalcidol can be considered to inhibit the rebound of iPTH and avoid an excessive decrease in serum calcium when the patient has hypocalcemia. As shown in literature, maybe it is timing of vitamin D and calcium supplements in the first 2 weeks especially finding calcium decrease to the lower limit of normal range 17 . The most appropriate time of vitamin D and calcium supplements after denosumab administration still needs more research.…”

“…As shown in literature, maybe it is timing of vitamin D and calcium supplements in the first 2 weeks especially finding calcium decrease to the lower limit of normal range. 17 The most appropriate time of vitamin D and calcium supplements after denosumab administration still needs more research.…”

“…In contrast to hypocalcemia, some cases reported rebound-linked hypercalcemia and multiple vertebral fractures due to discontinuation of denosumab. 17,18 The rebound effect generally occurred several months after stopping treatment in oncological patients taking a large dose of denosumab or patients with osteoporosis taking it for long-term treatment. 19,20 Our patient also experienced an increase in calcium 3 months after denosumab, but another injection was recommended.…”

Is Adynamic Bone Always a Disease? Lessons from Patients with Chronic Kidney Disease

“…In a recent RCT, treatment with denosumab or alendronate for 12 months improved BMD and did not affect the health of blood vessels (including scores of VC) in patients on dialysis [ 145 ]. Several studies showed that the fracture risk increases after discontinuation of denosumab in osteoporotic women with normal kidney function [ 179 , 180 , 181 , 182 , 183 , 184 ]. Studies addressing this concern in CKD are lacking.…”

Treatment of central giant cell granuloma with denosumab: A case report of a complicated treatment course

“…Based on these findings and earlier reports in literature, a diagnosis of exclusion of severe hypercalcaemia as a result of rebound hyperactivation of osteoclasts after discontinuation of denosumab was put forward. [5][6][7][8] The origin of the acute kidney injury was related to the profound hypercalcaemia. Hyperhydration and a low-calcium diet were initiated which was followed by a partial recovery of the kidney function (eGFR 74 ml/min/m 2 ).…”