Non-Cochrane · other · PM42929987
RANK/RANKL/OPG Axis Expression and Response to Anti-RANKL Therapy in Gnathic Giant Cell Lesions: A Systematic Review and Meta-Analysis.
Mahmood Darya Khalid, Hama Arivan Mahmood, Hashmi Ahmad Shoeb · Diseases (Basel, Switzerland) · 2026 · PubMed · doi:10.3390/diseases14100360
Findings
6 findings
| Population | ||||
|---|---|---|---|---|
| Central giant cell granuloma of the jaws | Non-aggressive phenotype | Aggressive phenotype | RANK staining intensity-distribution score | SMD 0.55 [-0.00, 1.11] GRADE not reported 2 studies · 58 participants |
| Central giant cell granuloma of the jaws | Non-aggressive phenotype | Aggressive phenotype | RANK-positive cell percentage | SMD 0.25 [-0.29, 0.80] GRADE not reported 2 studies · 58 participants |
| Gnathic giant cell lesions | Denosumab | None | Adverse effects During and after treatment | no estimate extracted GRADE not reported Studies not reported |
| Gnathic giant cell lesions | Denosumab | None | Recurrence after cessation After treatment cessation | no estimate extracted GRADE not reported Studies not reported |
| Gnathic giant cell lesions | Denosumab | None | Clinical and radiological tumor response Unresolved: the two extractors disagree on this row. | no estimate extracted GRADE not reported 10 studies · 58 participants |
| Giant cell lesions of the jaws | Central giant cell granuloma | Peripheral giant cell granuloma | RANKL expression | no estimate extracted GRADE not reported 1 study · 40 participants |
Included primary studies 21
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Ahmed 2016 Immunohistochemical detection of the receptor activator of nuclear factor Kappa B ligand and c-fos in giant cell granuloma. PMID:27194861 | 2016 | this review only | not stated | not extracted yet |
| Bar Droma 2020 Positive Outcomes of Denosumab Treatment in 2 Patients With Cherubism. PMID:32649899 | 2020 | this review only | Clinical and radiological tumor response | not extracted yet |
| Choe 2021 Treatment of central giant cell granuloma in children with denosumab. PMID:33089644 | 2021 | this review only | Clinical and radiological tumor response | not extracted yet |
| Fanourakis 2010 Expression of receptor activator of NF-κB ligand and osteoprotegerin in peripheral giant cell granulomas of the jaws. PMID:20701665 | 2010 | this review only | not stated | not extracted yet |
| Friedrich 2010 Expression of proteases in giant cell lesions of the jaws, tendon sheath and salivary glands. PMID:20592356 | 2010 | this review only | not stated | not extracted yet |
| Hameed 2019 Management of an aggressive giant cell granuloma of the mandible with denosumab: a case report. PMID:31230854 | 2019 | this review only | not stated | not extracted yet |
| Hosur 2018 Clinicopathological profile of central giant cell granulomas: An institutional experience and study of immunohistochemistry expression of… PMID:30158768 | 2018 | this review only | not stated | not extracted yet |
| Kadlub 2018 Molecular and cellular characterizations of human cherubism: disease aggressiveness depends on osteoclast differentiation. PMID:30236129 | 2018 | this review only | not stated | not extracted yet |
| Kawamura 2020 Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism. PMID:32649295 | 2020 | this review only | not stated | not extracted yet |
| Li 2003 Multinucleated giant cells in various forms of giant cell containing lesions of the jaws express features of osteoclasts. PMID:12787044 | 2003 | this review only | not stated | not extracted yet |
| Martini 2018 Immunohistochemical expression of RANKL in oral giant cell lesions is predictive of aggressiveness. PMID:30379236 | 2018 | this review only | not stated | not extracted yet |
| Morais 2019 Peri-implant peripheral giant cell lesions: report of 13 new cases and comparative histological and immunohistochemical analysis with… PMID:31655833 | 2019 | this review only | not stated | not extracted yet |
| O'Connell 2015 Aggressive giant cell lesion of the jaws: a review of management options and report of a mandibular lesion treated with denosumab. PMID:26340897 | 2015 | this review only | not stated | not extracted yet |
| Rhou 2022 Clinical and Radiologic Response of Central Giant Cell Granuloma to Denosumab: A 6-Year Prospective Observational Study. PMID:35088118 | 2022 | this review only | Clinical and radiological tumor response | not extracted yet |
| Schreuder 2022 RANKL inhibition for giant cell lesions of the jaw: A retrospective cohort analysis. PMID:36174298 | 2022 | this review only | Clinical and radiological tumor response | not extracted yet |
| Sergio 2005 Immunohistochemical expression of RANK, GRalpha and CTR in central giant cell granuloma of the jaws. PMID:15878752 | 2005 | this review only | RANK-positive cell percentage | not extracted yet |
| Stagner 2019 Giant Cell Lesions of the Maxillofacial Skeleton Express RANKL by RNA In Situ Hybridization Regardless of Histologic Pattern. PMID:30998511 | 2019 | this review only | not stated | not extracted yet |
| Taher 2024 Bone Remodeling Regulators in Central Giant Cell Granuloma: a Study of RANK and Osteocalcin Epression DOI:10.31689/rmm.2024.31.4.317 | 2024 | this review only | RANK-positive cell percentage | not extracted yet |
| Upfill-Brown 2019 Use of Denosumab in Children With Osteoclast Bone Dysplasias: Report of Three Cases. PMID:31687646 | 2019 | this review only | Clinical and radiological tumor response | not extracted yet |
| Vanderniet 2022 Denosumab for central giant cell granuloma in an Australian tertiary paediatric centre. PMID:35331976 | 2022 | this review only | Clinical and radiological tumor response | not extracted yet |
| Ying Ko 2026 Central Giant Cell Granuloma: A Decade of Institutional Experience and Curative Potential of Neoadjuvant Denosumab. PMID:42301892 | 2026 | this review only | Clinical and radiological tumor response | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Histopathologically confirmed giant cell-containing lesions of the jaws: CGCG, PGCG and, where reported alongside these, cherubism and aneurysmal bone cyst; gnathic lesions only; human tissue | 11 tissue-marker studies (259 specimens; CGCG, PGCG, cherubism, ABC); 10 clinical denosumab studies (58 patients: 55 in 7 multi-patient cohorts, 3 single-case reports) |
| Intervention | Exposure: RANK, RANKL and OPG tissue expression assessed by IHC or ISH; therapy sub-question: treatment (anti-RANKL therapy) with clinical or marker response in the same cohort | RANK/RANKL/OPG expression by IHC (n=9) and ISH (n=2); denosumab therapy (n=10) |
| Comparison | Between-lesion comparison where reported (e.g., CGCG vs PGCG); within-lesion characterization where no comparator; for therapy sub-question, pre- vs post-treatment expression or expression stratified by treatment response | Aggressive vs non-aggressive CGCG (n=2 pooled); CGCG vs PGCG and other between-lesion comparisons (narrative); no comparator in denosumab studies |
| Outcomes | (a) Proportion of RANK/RANKL/OPG-positive cases, staining extent/intensity score, or mean expression +/- SD; (b) therapy administered and clinical/marker response | RANK-positive cell percentage (n=2); RANK SID score (n=2); cellular localization of RANK/RANKL/OPG (n=11, narrative); denosumab response, recurrence after cessation, rebound hypercalcemia (n=10, narrative) |
| Study designs | Original human tissue studies: clinical trials, prospective/retrospective cohorts, institutional case series (N >= 5); single-patient case reports synthesized separately for the therapy sub-question | Comparative tissue studies (n=7) and descriptive tissue case series (n=4); clinical prospective/retrospective cohorts and pediatric series (n=7) and case reports (n=3) |
| Timing | Not specified | Not specified |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | NR | Yes | no |
| 2Protocol established before the reviewcritical | NR | Yes | no |
| 3Choice of study designs explained | NR | No | no |
| 4Comprehensive literature searchcritical | NR | Partial Yes | no |
| 5Study selection in duplicate | NR | Yes | no |
| 6Data extraction in duplicate | NR | Yes | no |
| 7List of excluded studies with reasonscritical | NR | No | no |
| 8Included studies described in detail | NR | Yes | no |
| 9Risk of bias assessed satisfactorilycritical | NR | NRSI: Yes · RCT: N/A | no |
| 10Funding of included studies reported | NR | No | no |
| 11Appropriate meta-analysis methodscritical | NR | NRSI: No · RCT: N/A | no |
| 12Impact of risk of bias on the pooled results | NR | No | no |
| 13Risk of bias accounted for in interpretationcritical | NR | Yes | no |
| 14Heterogeneity explained | NR | Yes | no |
| 15Publication bias investigatedcritical | NR | No | no |
| 16Conflicts of interest reported | NR | Yes | no |
| Overall | NR | Critically Low | no |