A Paradigm Shift in the Management of Cherubism? A Preliminary Report Using Imatinib

Ricalde, Pat; Ahson, Imran; Schaefer, Samantha T.

doi:10.1016/j.joms.2019.02.021

Cited by 21 publications

(26 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We suggest also paying more attention to a potential cherubism systemic skeletal phenotype during patient management. If this systemic skeletal cherubism phenotype is confirmed, it would simplify treatment of severe cherubism patients and allay reservations about applying a systemic treatment such as those recently published (tacrolimus [34] or imatinib [35]), to a previously believed jaw-localised disease.…”

Section: Discussionmentioning

confidence: 91%

Cherubism as a systemic skeletal disease: evidence from an aggressive case

Morice

Joly²,

Ricquebourg

et al. 2020

BMC Musculoskelet Disord

View full text Add to dashboard Cite

Background: Cherubism is a rare autosomal dominant genetic condition caused by mutations in the SH3BP2 gene. This disease is characterized by osteolysis of the jaws, with the bone replaced by soft tissue rich in fibroblasts and multinuclear giant cells. SH3BP2 is a ubiquitous adaptor protein yet the consequences of SH3BP2 mutation have so far been described as impacting only face. Cherubism mouse models have been generated and unlike human patients, the knock-in mice exhibit systemic bone loss together with a systemic inflammation. Case presentation: In light of these observations, we decided to search for a systemic cherubism phenotype in a 6-year-old girl with an aggressive cherubism. We report here the first case of cherubism with systemic manifestations. Bone densitometry showed low overall bone density (total body Z-score = − 4.6 SD). Several markers of bone remodelling (CTx, BALP, P1NP) as well as inflammation (TNFα and IL-1) were elevated. A causative second-site mutation in other genes known to influence bone density was ruled out by sequencing a panel of such genes. Conclusions: If this systemic skeletal cherubism phenotype should be confirmed, it would simplify the treatment of severe cherubism patients and allay reservations about applying a systemic treatment such as those recently published (tacrolimus or imatinib) to a disease heretofore believed to be localised to the jaws.

show abstract

Section: Discussionmentioning

confidence: 91%

Cherubism as a systemic skeletal disease: evidence from an aggressive case

Morice

Joly²,

Ricquebourg

et al. 2020

BMC Musculoskelet Disord

View full text Add to dashboard Cite

show abstract

“…Alternatively intra-lesional injection of corticosteroids, systemic calcitonin, and interferon has been reported for the treatment of central giant cell granulomas of the jaw; but, they have shown variable results (31,32). More recently, oral imatinib has been used for treatment of isolated central giant cell lesions and those associated with cherubism (33); however, the data are limited to case reports and small series. The patients with NL/MGCLs in this study have shown excellent response in regression of the tumor with minimal side effects using denosumab.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Safety and Efficacy of Denosumab in Four Children With Noonan Syndrome With Multiple Giant Cell Lesions of the Jaw

et al. 2020

View full text Add to dashboard Cite

Noonan syndrome is a genetic disorder caused by mutations in the RAS/MAPK pathway. Multiple giant cell lesions are a rare sequelae of disruptions in this pathway, termed Noonan-like multiple giant cell lesions (NL/MGCLs). Medical management of these tumors rather than surgical intervention is preferential as the lesions are benign but locally destructive and recurring. This case series describes four male pediatric patients with Noonan syndrome and multiple giant cell lesions of the jaw treated with denosumab, a monoclonal antibody to receptor activator of nuclear factor kappa B ligand (RANKL), which has been approved for the treatment of malignant giant cell tumors in adults but not evaluated for safety or efficacy in children. All four pediatric patients responded clinically and radiographically to the treatment. Adverse events occurred in a predictable pattern and included hypocalcemia and joint pain during the initiation of treatment and symptomatic hypercalcemia after the cessation of treatment. Growth was not significantly impaired in these skeletally immature patients. This case series demonstrates how a weight-adjusted denosumab dose can effectively treat NL/MGCLs and provides laboratory data for consideration of the timing of monitoring for known side effects.

show abstract

“…This genetic disorder is related to mutations in the SH3BP2 gene encoding a tankyrase substrate. 110,111 An off-label therapeutic role of N-acetylcysteine (N-Ac) is currently being tested in diastrophic dysplasia (DTD), a severe nonlethal chondrodysplasia due to recessive mutations in the DTST gene, a cell membrane sulfate-chloride antiporter, which allows the recruitment of sulfate from the extracellular space into the cytoplasm. Preclinical studies showed promising results of N-Ac administration that acts as an intracellular sulfate source for macromolecular sulfatation in mouse models of DTD.…”

Section: Other Potentials Therapies Investigated In Animal Modelsmentioning

confidence: 99%

“…This genetic disorder is related to mutations in the SH3BP2 gene encoding a tankyrase substrate. 110,111…”

Section: X-linked Hypophosphatemiamentioning

confidence: 99%

New perspectives on the treatment of skeletal dysplasia

Marzin

Cormier‐Daire

2020

Therapeutic Advances in Endocrinology

View full text Add to dashboard Cite

The last few decades have been marked by the identification of numerous genes implicated in genetic disorders, helping in the elucidation of the underlying pathophysiology of these conditions. This has allowed new therapeutic approaches to emerge such as cellular therapy, gene therapy, or pharmacological therapy for various conditions. Skeletal dysplasias are good models to illustrate these scientific advances. Indeed, several therapeutic strategies are currently being investigated in osteogenesis imperfecta; there are ongoing clinical trials based on pharmacological approaches, targeting signaling pathways in achondroplasia and fibrodysplasia ossificans progressiva or the endoplasmic reticulum stress in metaphyseal dysplasia type Schmid or pseudoachondroplasia. Moreover, the treatment of hypophosphatasia or Morquio A disease illustrates the efficacy of enzyme drug replacement. To provide a highly specialized multidisciplinary approach, these treatments are managed by reference centers. The emergence of treatments in skeletal dysplasia provides new perspectives on the prognosis of these severe conditions and may change prenatal counseling in these diseases over the coming years.

show abstract

A Paradigm Shift in the Management of Cherubism? A Preliminary Report Using Imatinib

Cited by 21 publications

References 9 publications

Cherubism as a systemic skeletal disease: evidence from an aggressive case

Cherubism as a systemic skeletal disease: evidence from an aggressive case

Case Report: Safety and Efficacy of Denosumab in Four Children With Noonan Syndrome With Multiple Giant Cell Lesions of the Jaw

New perspectives on the treatment of skeletal dysplasia

Contact Info

Product

Resources

About