Hypercalcemia after discontinuation of long-term denosumab treatment

Sølling, Anne Sophie; Harsløf, Torben; Kaal, Andreas; Rejnmark, Lars; Langdahl, Bente

doi:10.1007/s00198-016-3535-5

Cited by 37 publications

(28 citation statements)

References 12 publications

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“…The most prevailing hypothesis is that of markedly increased bone turnover. It has been speculated that the rebound effect is more prominent as the number of denosumab doses increases . Thus, discontinuation after long‐term therapy may result in an even greater risk than discontinuation after only 2 years .…”

Section: Discussionmentioning

confidence: 99%

Clinical Features of 24 Patients With Rebound‐Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases

Anastasilakis

Polyzos

Makras

et al. 2017

J of Bone & Mineral Res

289

179

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We aimed to study the clinical and imaging characteristics of patients sustaining vertebral fractures after denosumab discontinuation. For this purpose, we conducted a computerized advanced literature search that identified 13 published cases, and we additionally included another 11 new cases from our centers. Twenty-four postmenopausal women with vertebral fracture(s) after denosumab discontinuation, experiencing 112 fractures in total, were analyzed. The mean number of fractures per patient was 4.7. The most commonly affected vertebrae were T12 and L1. All fractures occurred 8 to 16 months after the last denosumab injection. Eighty-three percent of the patients were treatment naïve, whereas 33% had prevalent vertebral fractures. Five (23%) patients were on concurrent aromatase inhibitor treatment. When patients were divided according to treatment duration with an arbitrary cut-off of 2 years, those with ≤2 years of denosumab treatment had fewer fractures compared with those with >2 years (mean ± SEM fractures 3.2 ± 0.7 versus 5.2 ± 1.4, p = 0.055). Vertebroplasty was used in 5 patients, resulting in additional clinical vertebral fractures in all cases. We conclude that vertebral fracture(s) after denosumab discontinuation are in the majority of patients multiples, and they occur a few months after the effect of the last dose is depleted. Therefore, patients should not delay or omit denosumab doses. Fractures are typically osteoporotic, located at the lower thoracic and the upper lumbar spine. Vertebroplasty is an unsuccessful treatment strategy for such patients. © 2017 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Clinical Features of 24 Patients With Rebound‐Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases

Anastasilakis

Polyzos

Makras

et al. 2017

J of Bone & Mineral Res

289

179

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“…Although no major side effects were observed during the treatment, two patients (22%) in our study developed severe hypercalcemia 5 months after the discontinuation of denosumab. There are several reported cases of hypercalcemia following cessation of denosumab treatment used for GCTB, fibrous dysplasia, and osteoporosis . In these cases, the etiology of hypercalcemia was thought to be related to rebound osteoclastic bone resorption and increase in bone turnover markers, both induced by rapid recovery of bone resorption and removal of inhibition of osteoclast formation.…”

Section: Discussionmentioning

confidence: 99%

Denosumab treatment in aneurysmal bone cyst: Evaluation of nine cases

Kurucu

Akyüz

Ergen

et al. 2017

Pediatric Blood & Cancer

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“…For example, in the child treated for fibrous dysplasia, serum C-telopeptide rebounded to 250% above the pre-denosumab baseline, necessitating bisphosphonate treatment for hypercalcemia; C-telopeptide then returned to baseline after 5 months. While hypercalcemia post-discontinuation of denosumab is described in one published report of an adult treated with long-term denosumab therapy [63], 5 cases have been reported in the much more limited pediatric literature (Table 1). This may be related to the higher baseline bone turnover in children, which could result in a proportionately greater rebound post-discontinuation.…”

Section: Safety and Tolerability Of Denosumab In Adults And Childrenmentioning

confidence: 99%

Denosumab: an Emerging Therapy in Pediatric Bone Disorders

Boyce

2017

Curr Osteoporos Rep

113

102

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Purpose of Review Denosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand (RANKL), and has emerged as an important novel therapy for skeletal disorders. This article examines the use of denosumab in children. Recent findings Considerable safety and efficacy data exists for denosumab treatment of adults with osteoporosis, bone metastases, and giant cell tumors. Pediatric data is limited; however, evidence suggests denosumab may be beneficial in decreasing bone turnover, increasing bone density, and preventing growth of certain skeletal neoplasms in children. Denosumab’s effect on bone turnover is rapidly reversible after drug discontinuation, representing a key difference from bisphosphonates. Rebound increased bone turnover has led to severe hypercalcemia in several pediatric patients. Summary Denosumab is a promising therapy for pediatric skeletal disorders. At present, safety concerns related to rebounding bone turnover and mineral homeostasis impact use of denosumab in children. Research is needed to determine if and how these effects can be mitigated.

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Hypercalcemia after discontinuation of long-term denosumab treatment

Cited by 37 publications

References 12 publications

Clinical Features of 24 Patients With Rebound‐Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases

Clinical Features of 24 Patients With Rebound‐Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases

Denosumab treatment in aneurysmal bone cyst: Evaluation of nine cases

Denosumab: an Emerging Therapy in Pediatric Bone Disorders

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