Denosumab in pediatric bone disorders and the role of RANKL blockade: a narrative review

Wang, Daoxi; Tang, Xueyang; Shi, Qingjiang; Wang, Ruifeng; Tao, Jianhua; Tang, Xiaodong; Guo, Wei

doi:10.21037/tp-22-276

Cited by 8 publications

(7 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The RANK signalling pathway has a critical role in tumour advancement 5 19–21. Thus, inhibiting this pathway with denosumab has proven to have activity in ABCs with rare, but serious side effects, such as hypercalcaemia and hypocalcaemia, as in our patients 5 22–24…”

Section: Discussionmentioning

confidence: 90%

Denosumab and sclerotherapy for recurrent spinal aneurysmal bone cyst in a child

Singh,

Madasswery,

Colman

et al. 2024

BMJ Case Rep

View full text Add to dashboard Cite

Aneurysmal bone cyst (ABC) is a non-malignant, locally destructive, blood-filled lesion in the bone that tends to grow aggressively. A young girl presented with a rapid recurrence after aggressive surgery of a large symptomatic sacral-spinal ABC. After a multidisciplinary tumour board, she was successfully treated with sclerotherapy and monthly intravenous denosumab. The patient has maintained asymptomatic for over 36 months now and has returned to full activity and strength. She never required surgery and has had radiologic resolution of the lesions. Treatment of recurrent ABC requires a multidisciplinary team approach. We believe this to be the first report to use this combined therapy to provide an alternative to morbid surgery for children with ABCs.

show abstract

Section: Discussionmentioning

confidence: 90%

Denosumab and sclerotherapy for recurrent spinal aneurysmal bone cyst in a child

Singh,

Madasswery,

Colman

et al. 2024

BMJ Case Rep

View full text Add to dashboard Cite

show abstract

“…An attempt to mitigate the protein product of the mutated SH3BP2 gene by a c-abl inhibitor (imatinib) demonstrated a partial regression of lesions in four pediatric cherubism cases. [49,50] Most treatments were found to be well tolerated, and many of the known adverse effects [49,[51][52][53][54][55][56] 56 ] were not observed, apart from a serious hypocalcemia and rebound hypercalcemia that occurred in three denosumab cases. [46,47,57] Although the drugs with positive outcomes mentioned in these incidental reports are promising, it is difficult to make a meaningful comparison with our results due to the lack of a comparative and systematic analysis.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Toxicity of Calcitonin Treatment in Children with Cherubism: A Single-Center Cohort Study

Schreuder,

Meijer,

Cleven

et al. 2023

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Cherubism is a rare autosomal dominant disease characterized by expansile osteolytic jawbone lesions. The effect and safety of off‐label calcitonin treatment during the progressive phase of the disease are not well described. In this retrospective study, we present data on the radiological response and adverse effects of subcutaneously administered calcitonin in a cohort of nine cherubism children (3 female, 6 male). Two of the nine patients underwent two separate treatment courses with a significant off‐treatment interval in between; therefore, a total of 11 treatment courses with a mean duration of 17.9 months (range <1–35, SD 10.8) were studied. To measure response, the cumulative volume of cherubism lesions was calculated from available three‐dimensional imaging. The primary outcome was the change in the volume of lesions during calcitonin treatment and only assessed for the eight treatment courses with a minimal duration of 6 months. A statistically significant reduction in the mean cumulative volume of lesions was seen regardless of treatment duration. Average volume reduction was highest in the first half year of treatment, with a gradual, ongoing reduction thereafter. For the secondary outcome, the change in the cumulative volume of lesions after treatment cessation was assessed for the seven treatment courses with follow‐up imaging available. After six of these seven treatment courses, the cumulative volume increased again but remained undoubtedly smaller than the initial volume at the start of therapy. Adverse effects were assessed for all 11 treatment courses and occurred in 73% of them. Most adverse effects were mild and low grade, with the most severe being one grade 3 symptomatic hypocalcemia requiring hospitalization and early treatment termination. Calcitonin treatment seems effective and tolerable in treating actively progressing cherubism in children. However, further research is required to better understand the pharmacological treatment of cherubism, including also other drugs, dosing, and protocols.This article is protected by copyright. All rights reserved.

show abstract

“…In fact, sclerotic epiphyseal bands appear during denosumab treatment parallel to the growing plate following some months of treatment ( 47 , 48 ). This seems, however, not to influence normal bone growth, the sclerotic band migrates distally and tends to disintegrate with time following cessation of denosumab treatment ( 49 , 47 ). There is also a theoretical risk of impaired fracture healing but it could not be observed in the case report from ( 48 ).…”

Section: The Efficacy Of Denosumab Treatmentmentioning

confidence: 99%

“…This may occur 4–7 months after discontinuation of the treatment. Hence, Wang et al ( 49 ) suggest close monitoring of bone metabolism markers and education of the parents regarding the common symptoms of hypercalcaemia. The best treatment for hypercalcaemia appears to be administration of low-dose bisphosphonates to patients with normal renal function, otherwise treatment with hyperhydration and calcitonin is preferred ( 50 ).…”

Section: The Efficacy Of Denosumab Treatmentmentioning

confidence: 99%

“…Some authors used standard doses and interval treatment for adolescents over 15 years of age and 45 kg ( 50 ), or for children with GCTB. Others reduced the dose (half of the standard dose or 1–1.5 mg/kg monthly) and extended the flexible interval (from 8 to 20 weeks) taking into consideration the diagnosis and the planned duration of the denosumab treatment ( 49 ). In conclusion, the data discussed here are mostly drawn from case series; so larger clinical trials are warranted to define the optimal dose and interval of denosumab treatment in children.…”

Section: The Efficacy Of Denosumab Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Current indications for denosumab in benign bone tumours

Imre,

Zoltán,

Miklós

2023

EFORT Open Reviews

View full text Add to dashboard Cite

Denosumab is a fully humanised monoclonal antibody to RANK ligand, inhibiting the RANK–RANKL pathway. It promotes the apoptosis of osteoclast-like giant cells, a secondary ossification and connective tissue formation. Given its high efficacy, denosumab is the standard treatment of unresectable or metastatic giant cell tumour of bone (GCTB) requiring morbid surgery. Neoadjuvant administration of denosumab may be justified to enable the resection of the tumour in certain cases; it should be considered, however, with caution for joint-saving surgery due to high local recurrence rates. In cases of unresectable or metastatic GCTB, however, denosumab treatment should be administered for years or even as a lifelong therapy. This poses many yet unanswered questions concerning the frequency of denosumab treatment as well as the ratio of the adverse events in the following years. Denosumab suppresses, not directly targets, the neoplastic stromal cells of GCTB. Ongoing in vitro studies suggest that other drugs alone or in combination (e.g. sunitinib) with denosumab may target both the neoplastic and the giant cells. Promising results have been reported regarding the off-label use of denosumab in other giant cell-rich tumours/tumour-like lesions, i.e. aneurysmal bone cysts and central giant cell granulomas. Data are derived, however, mostly from case reports and case series. Large prospective clinical trials are needed to evaluate the role and also the side effects of denosumab in the treatment of these rare diseases.

show abstract

Denosumab in pediatric bone disorders and the role of RANKL blockade: a narrative review

Cited by 8 publications

References 83 publications

Denosumab and sclerotherapy for recurrent spinal aneurysmal bone cyst in a child

Denosumab and sclerotherapy for recurrent spinal aneurysmal bone cyst in a child

Efficacy and Toxicity of Calcitonin Treatment in Children with Cherubism: A Single-Center Cohort Study

Current indications for denosumab in benign bone tumours

Contact Info

Product

Resources

About