Giant-cell tumor of bone: treatment options and role of denosumab

Singh, Arun S.; Chawla, Neal Shiv; Chawla, Sant P.

doi:10.2147/btt.s57359

Cited by 30 publications

(7 citation statements)

References 29 publications

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“…Denosumab interrupts the cycle of RANKL binding to osteoprotegerin and prevents the formation and function of osteoclasts [64]. Evidence suggests denosumab may be effective for treatment of giant cell tumors of bone, another disorder of BMSCs which is histologically similar to FD [65, 66]. RANKL is also reported to be overexpressed in a model of FD-like bone cells [6] and in FD tissue [67], suggesting this pathway may play a role in FD pathogenesis.…”

Section: Future Directionsmentioning

confidence: 99%

Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives

Robinson

Collins

Boyce

2016

Curr Osteoporos Rep

122

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Fibrous dysplasia (FD) is an uncommon and debilitating skeletal disorder resulting in fractures, deformity, functional impairment and pain. It arises from postzygotic somatic activating mutations in GNAS, in the cAMP-regulating transcript α-subunit, Gsα. Constitutive Gs signaling results in activation of adenylyl cyclase and dysregulated cAMP production. In the skeleton this leads to the development of FD lesions with abnormal bone matrix, trabeculae, and collagen, produced by undifferentiated mesenchymal cells. FD may occur in isolation or in combination with extraskeletal manifestations, including hyperfunctioning endocrinopathies and café-au-lait macules, termed McCune-Albright syndrome (MAS). This review summarizes current clinical and translational perspectives in FD/MAS, with an emphasis on FD pathogenesis, natural history, pre-clinical and clinical investigation, and future directions.

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Section: Future Directionsmentioning

confidence: 99%

Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives

Robinson

Collins

Boyce

2016

Curr Osteoporos Rep

122

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“…Clinically, GCT and GCT/PDB show a different profile, regarding the frequency, the age-onset (20-40 yrs in GCT and >40 yrs in GCT/PDB) and the skeletal localization of the neoplasm [ 5 – 6 ]. Conventional GCT mainly affects the appendicular skeleton (distal femur, proximal tibia and knee in nearly 50% of cases) with a low likelihood of dissemination [ 6 – 7 ]; on the contrary, GCT/PDB affects the pagetic areas of the axial skeleton (skull, mandible and pelvis), with a preferential localization in the spine in PDB patients with multiple skeletal GCTs [ 5 ]. Conventional GCT standard treatments usually contemplate the surgery (curettage or resection) for the complete removal of the tumor [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

The distinct clinical features of giant cell tumor of bone in pagetic and non-pagetic patients are associated with genetic, biochemical and histological differences

et al. 2017

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Giant Cell Tumor of Bone (GCT) is a tumor characterized by neoplastic mesenchymal stromal cells and a high number of osteoclast-like multinucleated giant cells. Rarely, GCT could arise in bones affected by Paget's disease of bone (GCT/PDB). Although it is already known that GCT/PDB and GCT show a different clinical profile regarding the age-onset and skeletal localization, our deep clinical comparison between the two GCT/PDB and GCT cohorts, permitted us to identify additional differences (e.g. focality, ALP serum levels, the 5-year survival rate and the familial recurrence), strongly suggesting a different molecular basis. Accordingly, driver somatic mutations in H3F3A and IDH2 were described in GCT patients, while we recently identified a germline mutation in ZNF687 as the genetic defect of GCT/PDB patients.Here, we detected H3F3A mutations in our GCT cohort, confirming its molecular screening as the elected diagnostic tool, and then we excluded the two-hit in H3F3A and IDH2 as the trigger event for the GCT/PDB development. Importantly, we also identified an alternative biochemical profile with GCT/PDB not exhibiting the up-regulation of the GCT marker FGFR2IIIc. Finally, our histological analysis also showed a different appearance of the two forms of the tumor, with GCT/PDB showing a higher number of osteoclast-like giant cells (twice), with an abnormal number of nuclei per cell, corroborating its different behaviour in terms of neoplastic properties.We demonstrated that the distinct clinical features of pagetic and conventional GCT are associated with different genetic background, resulting in a specific biochemical and histological behaviour of the tumour.

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“…Denosumab is the only drug approved by The United States Food and Drug Administration (FDA), for patients with unresectable, recurrent or metastatic GCTB, or in cases where surgery has a high risk of death [ 20 ]. Denosumab is a monoclonal antibody [immunoglobulin G2 (IgG2)] of fully human type, which decreases bone resorption by specific binding to the receptor activator of nuclear factor-kappa B ligand (RANK-L), which inhibits the RANK receptor [ 5 , 21 ].…”

Section: ⧉ Diagnosis and Treatment Options In Gctbmentioning

confidence: 99%

Depression and anxiety in recurrent giant cell tumor of bone

Popescu

Stoicea²,

Marinescu³

et al. 2021

Rom J Morphol Embryol

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Giant cell tumor of bone (GCTB) is a benign neoplasia more frequently encountered in young females. The pathogenic and evolutionary dynamics of the disease is strongly influenced by the presence of depression and cellular mechanisms, especially proinflammatory and immune. Although it is not a malignant tumor, it is often recurrent, which determines a high level of depression, anxiety, and fear of the patients. Cytokine mechanisms, especially through increased tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6), as well as the involvement of the receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANK-L) system, can be correlated with the risk of malignancy. Unfavorable evolution is associated with persistent pain, difficulties of movement and body dysmorphic symptoms. The diagnosis is based mainly on histopathological (HP) assessment. The patients can be treated with pharmacological agents (Denosumab), surgery with tumor excision, reconstruction or osteosynthesis, and radiotherapy. Patients with GCTB require HP and imaging evaluations, especially of relapses, to detect the risk of metastasis or malignancy, simultaneously with psychological and psychiatric monitoring to detect depression, addictive behaviors, and suicide risk. It is necessary to evaluate in a multidisciplinary team to avoid unfavorable oncological and psychiatric developments. Through its clinical, HP, and therapeutic features, GCTB has multiple connections with the psychological and psychopathological dimension.

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Giant-cell tumor of bone: treatment options and role of denosumab

Cited by 30 publications

References 29 publications

Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives

Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives

The distinct clinical features of giant cell tumor of bone in pagetic and non-pagetic patients are associated with genetic, biochemical and histological differences

Depression and anxiety in recurrent giant cell tumor of bone

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