Giant cell tumor of bone (GCTB) is a rare, locally aggressive neoplasm that should be treated surgically, whenever possible. This treatment approach may be linked with greater morbidity besides functional impairment. Denosumab is a human monoclonal antibody. Its administration inhibits bone resorption and has become part of the therapeutic armamentarium against GCTB, as it allows local control with a view to downstaging for a more conservative surgical procedure. However, there is no consensus in the literature regarding the optimal denosumab regimen for GCTB. Therefore, a wide discussion of denosumab regimen is necessary.

To assess the effectiveness of various therapy protocols employing denosumab in individuals with GCTB.

A broad and systematic literature search was carried out using the PRISMA guidelines. We analyzed studies that reported skeletally mature patients with GCTB regardless of sex or ethnicity treated with denosumab. Articles with fewer than five patients and in languages except Spanish, Portuguese and English were excluded. Statistical analysis with proportion meta-analysis was performed due to the dichotomous nature of the data.

1005 articles were screened, of which 26 articles met the inclusion criteria and were selected, totaling 1742 patients, 51.8% women and 48.2% men, with an average of 35 years of age. Treatment with denosumab was associated with high rates of clinical benefit (CB) and imaging response (IR), without changing local recurrence rates when compared to patients treated without denosumab, regardless of the therapeutic regimen adopted and the number of doses applied. The adverse events (AE) presented were mostly mild, with the exception of a malignant transformation to osteosarcoma.

Treatment of GCTB with denosumab is effective, showing high rates of CB and IR. The AE that occurred were mostly mild. We found no differences between the articles considering the researched outcomes regardless of the therapeutic regimen adopted.

• Bone neoplasms
• Denosumab
• Outcome assessment health care
• Giant cell tumor of bone
• Systematic review

• case report
• chondrosarcoma-like
• giant cell tumors
• malignant
• rib

• Bisphosphonate
• Knee joint
• Long bone
• Osteoclastoma
• RANK ligand
• Tumor

• Denosumab/therapeutic use
• Fibula
• Giant Cell Tumor of Bone/drug therapy
• Giant Cell Tumor of Bone/pathology

• Humans
• Fibula/diagnostic imaging
• Giant Cell Tumor of Bone/pathology
• Giant Cell Tumor of Bone/diagnostic imaging
• Bone Neoplasms/diagnostic imaging
• Bone Neoplasms/pathology
• Male
• Female

• bone
• giant cell tumor
• lung metastases
• oncologic outcomes
• treatment

• Humans
• Denosumab/therapeutic use
• Lung Neoplasms/drug therapy
• Giant Cell Tumor of Bone/drug therapy
• Male
• Female
• Bone Neoplasms/secondary
• Bone Neoplasms/drug therapy
• Adult
• Middle Aged
• Young Adult
• Adolescent
• Child

• Giant cell tumor (GCT)
• Sphenoid bone

• Bone Neoplasms
• Curettage
• Giant Cell Tumor of Bone
• Recurrence

• Denosumab
• En bloc spondylectomy
• Giant cell tumor of bone
• Spinal neoplasms

• Humans
• Denosumab/therapeutic use
• Retrospective Studies
• Ki-67 Antigen
• Spinal Neoplasms
• Neoplasm Recurrence, Local/drug therapy
• Spine/pathology
• Giant Cell Tumors
• Treatment Outcome

• 2016YFC0902100 National Key Research and Development Project of China
• 19411962700 Science and Technology Commission of Shanghai Municipality
• 21MMC1930100 Science and Technology Commission of Shanghai Municipality
• 21QNPY044 the Logistics Support Department of PLA
• Science and Technology Commission of Shanghai Municipality

• Case report
• Denosumab
• Giant cell tumor of bone
• Mandible
• Oral surgery

• adjuvant therapy
• curettage
• en-bloc resection
• giant cell tumor
• recurrence rate
• second recurrence
• treatment

• bone giant cell tumor
• drug treatment
• fracture healing
• potential drugs
• potential genes

• Denosumab
• Giant cell tumour of bone
• H3F3A
• Tumor de células gigantes óseo

• Humans
• Female
• Adult
• Giant Cell Tumor of Bone/drug therapy
• Giant Cell Tumor of Bone/pathology
• Bone Neoplasms/drug therapy
• Bone Neoplasms/pathology
• Chest Pain/diagnostic imaging
• Chest Pain/etiology
• Biopsy
• Tomography, X-Ray Computed
• Denosumab/therapeutic use
• Bone Density Conservation Agents/therapeutic use
• Treatment Outcome

• Bone
• denosumab
• giant cell tumor
• regression

• Male
• Female
• Young Adult
• Humans
• Adult
• Denosumab/pharmacology
• Denosumab/therapeutic use
• RANK Ligand/therapeutic use
• Giant Cell Tumor of Bone/drug therapy
• Giant Cell Tumor of Bone/pathology
• Bone Neoplasms/drug therapy
• Bone Neoplasms/pathology
• Fibrosis
• Bone Density Conservation Agents/therapeutic use

Background: Giant cell tumors (GCTs) are locally aggressive but rarely malignant bone neoplasms that uncommonly involve the skull. In this report, we describe a tumor of the sphenoid sinus. Case presentation: A 51-year-old female was presented with headache, and bilateral decreased visual acuity, CT scan, and brain MRI revealed an infra-sellar enhancing tumor expanding to the sellar and supra-sellar region which proved to be a GCT. the patient had received 03 months of preoperative denosumab-based treatment and imaging follow-up showed regression in size and morphology modifications of tumor tissue. Conclusion: This is one of few reports to describe the appearance of sphenoid bone GCT, and the first report to highlight the effects of short-term denosumab treatment in GCTb in such a location.

This study reports a large single-center series of primary bone tumors of the spine (PBTs). We aimed to review the concepts for management, as this kind of tumor represents a very rare entity, and also propose a new treatment algorithm. Retrospective analysis revealed 92 patients receiving surgery for PBTs from 2007 to 2019 at our center. They were analyzed based on surgical management and the course of the disease. A total of 145 surgical procedures were performed (50 cervical, 46 thoracic, 28 lumbar, and 21 sacral). Complete tumor resection was achieved in 65%, of which 22% showed tumor recurrence during follow-up (mean time to recurrence 334 days). The five-year mortality rate was significantly lower after complete resection (3% versus 25% after subtotal resection). Most of the patients improved in their symptoms through surgery. Regarding the tumor entity, the most common PBTs were vertebral hemangiomas (20%), osteoid osteomas (15%), and chordomas (16%). The Enneking graduation system showed a good correlation with the risk of recurrence and mortality. Complete resection in PBTs increased survival rates and remains the method of choice. Thus, quality of life—especially with a higher extent of resection—should be considered.

Giant cell tumors of bone (GCTB) are associated with massive bone destructions and high recurrence rates. In a previous study, we observed cytotoxic effects of three different compositions of bioactive glasses (BGs) towards GCTSC but not bone marrow derived stromal cells (BMSC) indicating that BGs represent promising candidates for the development of new therapeutic approaches. In the current study we aimed to investigate the molecular mechanisms that are involved in BG induced cytotoxicity. We observed, that BG treatment was not associated with any signs of apoptosis, but rather led to a strong induction of mitogen activated protein kinases (MAPK) and, as a consequence, upregulation of several transcription factors specifically in GCTSC. Genome wide gene expression profiling further revealed a set of fifteen genes that were exclusively induced in GCTSC or induced significantly stronger in GCTSC compared to BMSC. BG treatment further induced autophagy that was significantly more pronounced in GCTSC compared to BMSC and could be inhibited by MAPK inhibitors. Together with the known osteogenic properties of BGs our findings support the suitability of BGs as therapeutic agents for the treatment of GCTB. However, these data have to be verified under in vivo conditions.

•

Bioactive glasses (BG) are selectively cytotoxic towards neoplastic stromal cells.

• Autophagy
• BG, bioactive glass
• BMSC, bone marrow derived stromal cell
• Bioactive glass
• Cytotoxicity
• GCTB, giant cell tumor of bone
• GCTSC, giant cell tumor derived stromal cell
• Giant cell tumor of bone
• MAPK, mitogen activated protein kinases
• Mesenchymal stromal cells
• Mitogen-activated protein kinases

Background: Giant cell tumors of the bone (GCTB) are rare, benign, aggressive, recurrent tumors that are most often found at the ends of long bones. They account for 5% of all primary bone tumors and 20% of all benign bone tumors. The clinical features of GCTB include local swelling, pain, and limitations in joint movement. Approximately half of GCTB arise around the knee joint, affecting either the distal femur or proximal tibia. Tissue biopsy reveals an excess of multinucleated giant cells on a stromal cell background, indicating a diagnosis. Intralesional curettage is used to treat GCTB and is associated with minimal disability; however, local recurrence may occur in many patients. Resection and endoprosthetic repair or bone graft reconstruction are often used to treat GCTB near the joint. To our knowledge, there are currently no studies on this topic in the city of Jeddah, where we conducted our study. Our aim was to evaluate the outcome of surgical resection accompanied by denosumab injection compared to that of surgery alone in treating GCTB.

Methods: All cases of GCTB at King Abdulaziz Medical City, Jeddah, between January 2008 and December 2018, that fulfilled the inclusion and exclusion criteria were included. All cases of GCTB in the pre-specified period were classified as surgical resection with denosumab injection or surgical resection alone. The outcomes of the two modalities were compared. Recurrence was investigated in patients belonging to both the groups.

Results: Twenty-six cases that met the inclusion criteria were included in the study and the data were analyzed. The subjects were divided into two groups: denosumab and surgery (n = 7) and surgery alone (n = 19). Patients treated with denosumab and surgery had a higher recurrence rate (57%); however, the difference was not significant (p = 0.407).

Conclusion: Our study showed that when comparing local recurrence after curettage in patients treated with denosumab and patients who did not receive it, preoperative denosumab therapy was associated with an increased incidence of local recurrence. We recommend a systematic review that can include more studies in this field to acquire more definitive results regarding this topic.

• Bone curettage
• Bone tumor
• Giant cell tumor of bone
• Tumor recurrence

The widely accepted local therapy in extremity giant cell tumor of bone (GCTB) is surgery, in the form of extended intralesional curettage with adequate disease clearance and retention of the limb, wherever possible. Denosumab is a relevant therapy option for advanced GCTB, to benefit tumor response and surgical down-staging. Most GCTB patients with localized disease can be successfully treated with surgical curettage; patients with primary unresectable lesions or metastases may experience long-term clinical and radiological remission and pain control with denosumab treatment, and in this clinical situation, denosumab is currently the treatment of choice.

(1) Despite the benign nature of the giant cell tumor of bone (GCTB), it shows a local recurrence rate of up to 50% and a chance of malignant transformation. The widely accepted local therapy in extremity GCTB is surgery, in the form of extended intralesional curettage with adequate disease clearance and retention of the limb, wherever possible. Denosumab, a human monoclonal antibody directed against the RANKL and associated inhibition of the RANKL pathway, is a relevant therapy option for advanced GCTB, to benefit tumor response and surgical down-staging. (2) The literature review of patients with GCTB treated with denosumab is performed via PubMed, using suitable keywords from January 2009 to January 2021. (3) Current indications for denosumab use are not definitively clear and unambiguous. Most GCTB patients with localized disease can be successfully treated with surgical curettage, and the role of denosumab in preoperative therapy in this patient population remains unclear. (4) However, patients with primary unresectable lesions or metastases may experience long-term clinical and radiological remission and pain control with denosumab treatment, and in this clinical situation, denosumab is currently the treatment of choice.

• Bone tumour
• Fibrosarcoma
• Giant cell tumour of bone
• Malignant giant cell tumour of bone
• Osteosarcoma

• Benign bone tumors
• Bony tumors of orbit
• Paranasal sinuses
• Skull base

• Humans
• Male
• Orbit
• Osteoma/diagnostic imaging
• Osteoma/surgery
• Osteomyelitis
• Paranasal Sinus Neoplasms/diagnostic imaging
• Paranasal Sinus Neoplasms/pathology
• Paranasal Sinus Neoplasms/therapy
• Paranasal Sinuses/pathology
• Skull Base/diagnostic imaging
• Skull Base Neoplasms/diagnostic imaging
• Skull Base Neoplasms/therapy

There is a controversy over the medical treatment of unresectable spinal giant cell tumour (GCT) regarding dosing and duration. We studied a spinal GCT case that had expanded to the thoracic spinal canal and mediastinum and was successfully treated by surgical decompression and denosumab. A woman in her 30s presented with weakness in both the lower extremities. MRI revealed a large tumour in the posterior mediastinum expanding from the thoracic vertebrae (T3–6), which compressed the spinal cord. The patient underwent urgent spinal decompression with instrumentation and her tissue was sent for a pathology study. Histologically and immunohistochemistry confirmed the diagnosis of GCT. Since it was an unresectable tumour, this patient was treated with denosumab. Her neurological problem resolved after 6 months of treatment. After 4 years of follow-up, the patient displayed no further progression and no side effects from long-term denosumab usage.

• Decompression, Surgical
• Denosumab/therapeutic use
• Female
• Giant Cell Tumors/surgery
• Humans
• Mediastinum/pathology
• Spinal Neoplasms/diagnostic imaging
• Spinal Neoplasms/drug therapy
• Spinal Neoplasms/surgery
• Thoracic Vertebrae/pathology
• Treatment Outcome

• Japan
• curettage
• giant cell tumor of bone
• phase III
• preoperative denosumab

• Aneurysmal bone cyst
• denosumab
• osteoblastoma

• Aneurysmal bone cyst
• Children
• Fibrous dysplasia
• Proximal femur
• Simple bone cyst

• bone tumors
• denosumab
• giant-cell tumor of bone
• surgery

Spine giant cell tumors (SGCTs) are intermediate malignant bone tumors, sometimes aggressive and responsible for debilitating axial pain and sensorimotor impairments. Non-surgical therapies, including denosumab, radiotherapy, and selective arterial embolization (SAE), have shown promising results in the treatment of patients with inoperable SGCTs. In this systematic review, we aimed to comprehensively analyze the current literature on denosumab, radiotherapy, and SAE for inoperable SGCTs, comparing treatment outcomes and complications using a random-effect model meta-analysis. We found that all three treatments were equally effective in providing symptom improvement and radiological tumor response, also showing low and comparable rates of treatment-related complications. Patients treated with denosumab showed lower rates of local recurrences and distant metastases.

Background: Surgical resection remains the preferred treatment in spine giant cell tumors (SGCTs), but it is not always feasible. Conservative strategies have been studied for inoperable cases. We systematically reviewed the literature on inoperable SGCTs treated with denosumab, radiotherapy or selective arterial embolization (SAE). Methods: PubMed, Scopus, Web-of-Science, Ovid-EMBASE, and Cochrane were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to include studies of inoperable SGCTs treated with denosumab, radiotherapy or SAE. Treatment outcomes were analyzed and compared with a random-effect model meta-analysis. Results: Among the 17 studies included, 128 patients received denosumab, 59 radiotherapy, and 43 SAE. No significant differences in baseline patient characteristics were found between the three groups. All strategies were equally effective in providing symptom improvement (p = 0.187, I² = 0%) and reduction in tumor volume (p = 0.738, I² = 56.8%). Rates of treatment-related complications were low (denosumab: 12.5%; radiotherapy: 8.5%; SAE: 18.6%) and comparable (p = 0.311, I² = 0%). Patients receiving denosumab had significantly lower rates of local tumor recurrence (10.9%) and distant metastases (0%) compared to patients receiving radiotherapy (30.5%; 8.5%) or SAE (35.6%; 7%) (p = 0.003, I² = 32%; p = 0.002, I² = 47%). Denosumab was also correlated with significantly higher overall survival rates at 18 months (99.2%) and 24 months (99.2%) compared to radiotherapy (91.5%; 89.6%) and SAE (92.5%; 89.4%) (p = 0.019, I² = 8%; p = 0.004, I² = 23%). Mortality was higher in patients receiving SAE (20.9%) or radiotherapy (13.6%) compared to denosumab (0.8%) (p < 0.001), but deaths mostly occurred for unrelated diseases. Conclusions: Denosumab, radiotherapy, and SAE are safe and effective for inoperable SGCTs. Clinical and radiological outcomes are mostly comparable, but denosumab may provide superior tumor control.

• denosumab
• embolization
• giant cell tumor
• radiotherapy
• spine oncology

• bone tumor
• giant cell tumor of bone
• tenosynovial giant cell tumor

• Adolescent
• Adult
• Aged
• Bone Density Conservation Agents/adverse effects
• Bone Neoplasms/drug therapy
• Bone Neoplasms/pathology
• Giant Cell Tumor of Bone/drug therapy
• Giant Cell Tumor of Bone/pathology
• Humans
• Middle Aged
• Retrospective Studies
• Treatment Outcome
• Young Adult

• P30 CA046592 NCI NIH HHS
• University of Michigan Comprehensive Cancer Center

• Bone Density Conservation Agents/therapeutic use
• Bone Neoplasms/drug therapy
• Bone Neoplasms/surgery
• Denosumab/therapeutic use
• Giant Cell Tumor of Bone/diagnostic imaging
• Giant Cell Tumor of Bone/drug therapy
• Giant Cell Tumor of Bone/surgery
• Humans
• Neoplasm Recurrence, Local/prevention & control
• Retrospective Studies

• curettage
• denosumab
• giant cell tumor
• neo-adjuvant
• zoledronic acid

• Aneurysmal bone cyst
• Denosumab
• Recurrence
• Review

• Adult
• Bone Cysts, Aneurysmal/diagnostic imaging
• Bone Cysts, Aneurysmal/drug therapy
• Bone Cysts, Aneurysmal/pathology
• Bone Density Conservation Agents/therapeutic use
• Bone Neoplasms/drug therapy
• Bone and Bones/pathology
• Denosumab/therapeutic use
• Female
• Humans
• Hypercalcemia/chemically induced
• Infant, Newborn
• Male

• fibular strut arthrodesis
• foot
• giant cell tumor of bone
• hallux
• osteoclastoma
• toe phalanges
• wide resection

We elucidated clinicopathological characteristics of giant cell tumor of bone (GCTB) in Japan, and significant clinicopathological factors for predicting local recurrence. Clinicopathological profiles of 213 patients with GCTB (100 male, 113 female) involving extra‐craniofacial bones were retrieved. Pathological slides obtained at the initial surgery were reviewed. Fourteen pathological and five clinical features were statistically analyzed to disclose prognostic significance. Patient age ranged from 12–80 years (Average 38.7). Long bones were most frequently affected (86.4%), especially around the knee (62.9%). Histological features are basically similar to those previously reported. Within a follow‐up period (24–316 months, average 106.1 months), the local recurrence rate is 29.1%. Metastasis has occurred in 9 patients. Cox regression analysis of representative clinicopathological features shows that younger age, higher mitotic count, smaller zones of stromal hemorrhage, considerable vascular invasion and absence of ischemic necrosis are significant predictors for local recurrence. Initial operative method (curettage) is a significant risk factor in univariate analysis but not by multivariate analysis (P = 0.053). Denosumab administration increases risk but not significantly (P = 0.053). Histone 3.3 G34W immunopositivity is not significant for predicting local recurrence.

• G34W
• bone
• denosumab
• extra-craniofacial bone
• giant cell tumor of bone
• local recurrence
• mitosis
• prognosis
• risk factor
• statistical analysis

• Bone tumors
• Denosumab
• Giant cell tumor
• Neoplasia
• Tumor surgery

• denosumab
• giant cell tumor of bone
• meta-analysis
• osteoclastoma
• outcome

• McCune-Albright syndrome
• Metabolic bone diseases
• RANKL
• Skeletal neoplasms

• Bone Cysts, Aneurysmal/drug therapy
• Bone Density Conservation Agents/therapeutic use
• Bone Neoplasms/drug therapy
• Denosumab/therapeutic use
• Fibrous Dysplasia of Bone/drug therapy
• Giant Cell Tumor of Bone/drug therapy
• Humans

• ZIA DE000758 Intramural NIH HHS

• Combined anterior posterior hemivertebrectomy
• Congenital scoliosis
• Hemivertebrae
• Meta-analysis
• Posterior only hemivertebrectomy

•

En bloc resection with centralization is a viable approach in low-resource areas.

Giant cell tumor of bone (GCTB) is a benign-aggressive tumor that has a high-rate of recurrence with curettage resection alone. Patients with GCTB in underserved regions of the world can have progression of the tumor with significant disability due to a lack of specialty care. We present a case of an en bloc resection of an aggressive, recurrent GCTB of the radius with excellent function and no evidence of tumor recurrence two years after surgery.

A 22-year-old right-hand dominant female in Haiti developed an aggressive recurrence of a giant cell tumor of bone (GCTB) of the distal radius. Treatment consisted of en bloc resection of the distal radius with the proximal row of the carpus and centralization of the ulna. At two-year follow-up, the patient maintained good functional capacity with no clinical or radiological evidence of recurrence.

GCTB can cause significant destruction of the bone and articular surface if not treated adequately. Treatment options should be considered carefully in underserved regions of the world based on the resources available. This case exemplifies that complex limb-salvage surgery is possible when coordination of care between international and local surgeons is provided with an emphasis on continuity of care post-operatively.

En bloc resection with centralization of the ulna remains a viable technique to address aggressive GCTB of the distal radius and can be appropriate in resource-limited settings.

• Case report
• Centralization
• Giant cell tumor of bone
• Global health
• Haiti
• Radius

• Adult
• Bone Density Conservation Agents/therapeutic use
• Bone Neoplasms/drug therapy
• Bone Neoplasms/pathology
• Bone Neoplasms/surgery
• Curettage
• Denosumab/therapeutic use
• Female
• Giant Cell Tumor of Bone/drug therapy
• Giant Cell Tumor of Bone/pathology
• Giant Cell Tumor of Bone/surgery
• Humans
• Male
• Middle Aged
• Orthopedic Procedures
• Radius/pathology
• Radius/surgery
• Retrospective Studies
• Treatment Outcome
• Young Adult