P=N/A, N=500, Not yet recruiting, Xi'an Honghui Hospital of Xi'an Jiaotong University; Xi'an Honghui Hospital of Xi'an Jiaotong University

P4, N=200, Recruiting, Peking University First Hospital; Peking University First Hospital

P4, N=220, Not yet recruiting, Affiliated Hospital of Guangdong Medical University; Affiliated Hospital of Guangdong Medical University

P1, N=128, Completed, Taizhou Mabtech Pharmaceutical Co.,Ltd | Recruiting --> Completed

P=N/A, N=100, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P=N/A, N=517991, Completed, Amgen | Active, not recruiting --> Completed

P3, N=532, Completed, Alvotech Swiss AG | Active, not recruiting --> Completed

Seven cases with denosumab treatment demonstrated degrees of giant cell disappearance, increased fibrous tissue and reactive bone proliferation in the stroma... Pediatric GCTB predominantly affects females and occurs primarily in long bones, mainly around the knee joint, the majority of tumors predominantly arise in the epiphysis and extend into the metaphysis; however, in cases where the epiphyseal plates are still unclosed, the tumors may be restricted to the metaphysis. Detection of H3F3A gene mutation is crucial for the diagnosis and differential diagnosis of pediatric GCTB.

Genetic polymorphisms rs1800629 (TNF-α) and rs1054016 (RANKL) had a strong interaction and were associated with a lower risk to develop PAP.

P4, N=120, Recruiting, Prince of Wales Hospital, Shatin, Hong Kong

P3, N=440, Not yet recruiting, Xentria, Inc. | Trial completion date: Oct 2026 --> Oct 2027 | Initiation date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2026 --> Oct 2027

This manuscript discusses evidence from primary studies on HER2 and receptor activator of nuclear factor kappa-Β (RANK) signalling and drug responses and hypothesizes on possible mechanisms of synergism. Given that treatment of HER2-positive breast cancer has historically not involved RANK-L inhibition, this study may outline future areas of research in improving treatment algorithms, especially for bone-only metastatic disease.

Additionally, MALAT1 could be modified by NSUN2, an m5C methyltransferase, which in turn stabilized MALAT1 through the "reader" YBX1. Clinical studies indicated a notable positive correlation between MALAT1, NSUN2, YBX1 levels and bone destruction features, as well as with RANKL expression.

P4, N=35, Recruiting, Amgen | Trial completion date: Oct 2027 --> May 2028 | Trial primary completion date: Oct 2027 --> May 2028

P4, N=100, Not yet recruiting, Amgen

P3, N=514, Completed, Shanghai Henlius Biotech | Active, not recruiting --> Completed | Trial primary completion date: Apr 2024 --> Dec 2023

P=N/A, N=284, Not yet recruiting, Tangdu Hospital, Air Force Medical University; Tangdu Hospital, Air Force Medical University

P=N/A, N=100, Completed, The 2nd Affiliated Hospital of Chongqing Medical University; The 2nd Affiliated Hospital of Chongqing Medical University

P4, N=294, Not yet recruiting, The Third Affiliated Hospital of Southern Medical University; The Third Affiliated Hospital of Southern Medical University

P=N/A, N=300, Recruiting, Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital; Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital | Not yet recruiting --> Recruiting

P4, N=60, Active, not recruiting, Western University, Canada | Recruiting --> Active, not recruiting

Receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin(OPG) are critical regulators of bone metabolism, performing pleiotropic effects, and may have potential involvement in metabolic disorders like MASLD, resulting in a topic of great interest and intrigue. This narrative review aims to investigate this potential role and its implications in MASLD development and progression and in hepatocellular carcinoma, which represents its worst complication.

The current data support the assessment of TBL structures as a reliable prognostic tool in GCTB, potentially aiding in the development of personalized treatment strategies for patients.

P2, N=210, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting

P4, N=100, Recruiting, Amgen | Not yet recruiting --> Recruiting

Denosumab (DMB) is an effective anti-osteoporotic drug functions by inhibiting NF-κB ligand receptor-activating factor (RANKL)...In summary, RANKL/RANK deficiency may attenuate apoptosis of β-cells, a phenomenon associated with the TRAF3/NIK pathway. Therefore, RANKL/RANK could be regarded as a potential therapeutic strategy for DM.

The gene expression profiling revealed significant disparities in mRNA levels of IL-1β, IL-6, IL-4, IL-17a, RANKL, INF-γ, and TNF-α between the CFA-induced arthritis group and the control group. Consequently, it was inferred that gingerol-loaded PLGA NPs coated with chitosan exhibited heightened therapeutic efficacy in addressing CFA-induced arthritis in rats.

we suggest that the RANKL/OPG ratio could serve as a bone remodeling marker in ALL patients.

P1/2, N=45, Recruiting, City of Hope Medical Center | Trial completion date: Dec 2026 --> Apr 2026 | Trial primary completion date: Sep 2026 --> Apr 2026

These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.

P2, N=42, Completed, Alison Stopeck | N=30 --> 42

PRP mitigates cartilage degradation and inflammation in experimental knee OA by regulating the OPG/RANKL/RANK signalling system.

TGFβ1/STAT3 action was closely correlated with TNFSF11/TNFRSF11A axis-mediated airway remodeling. This study presented a novel strategy that blocks the TNFSF11/TNFRSF11A axis to exert a protective effect against asthma.

P3, N=86, Recruiting, Wuhan Union Hospital, China | Not yet recruiting --> Recruiting

The serum calcium level was reduced by denosumab, but the patient died 20 days after admission. The present case demonstrated the importance of considering oncological emergency, such as hypercalcemia and/or PTH-rP-producing hypercalcemia, in patients with adenocarcinoma.

Furthermore, in vitro assays demonstrated that JQ1 markedly inhibited osteoclast differentiation and function, underscoring the pivotal role of BRD4 in osteoclastogenesis and its potential as a target for therapeutic intervention in RA-induced bone destruction. Our study concludes that targeting BRD4 with the inhibitor JQ1 significantly mitigates inflammation and bone destruction in rheumatoid arthritis, suggesting that inhibition of BRD4 may be a potential therapeutic strategy for the treatment of bone destruction in RA.

Although unfit for curative therapy, the patient was treated with fluid replacement, bisphosphonates, calcitonin, and denosumab...This challenging case highlighted the rare but potentially fatal association of pNET with hypercalcemia. Hypercalcemia was the main cause of mortality in an otherwise relatively indolent malignancy.

This study highlights the potential clinical relevance of the RANK pathway in BC treatment, and our findings suggest that denosumab may offer significant benefits in terms of PFS and OS for certain subgroups, particularly those with HER2 scores of 1, patients under 60, and those with endocrine-resistant BC. In conclusion, considering that RANK pathway status may be a predictive biomarker for CDK4/6i treatment and may cause treatment resistance, our results demonstrate the clinical relevance of the combination of CDK4/6i + ET with RANKL inhibition.

P1/2, N=45, Recruiting, City of Hope Medical Center

P4, N=240, Active, not recruiting, Ottawa Hospital Research Institute | Recruiting --> Active, not recruiting | Trial completion date: Nov 2025 --> Jun 2026 | Trial primary completion date: Nov 2024 --> Jun 2025

P3, N=480, Completed, Biocon Biologics UK Ltd | Active, not recruiting --> Completed

P3, N=440, Not yet recruiting, Xentria, Inc.