P4, N=70, Recruiting, Aristotle University Of Thessaloniki | Trial completion date: Dec 2025 --> Sep 2026 | Trial primary completion date: Dec 2024 --> Sep 2025

P4, N=155, Active, not recruiting, Dong-A ST Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Feb 2025 --> Jul 2025 | Trial primary completion date: Feb 2025 --> Jul 2025

Our findings suggest that RANKL exerts different responses according to the expression of its receptors.

P4, N=45, Active, not recruiting, University of Alabama at Birmingham | Trial primary completion date: Dec 2024 --> Aug 2025

P4, N=60, Not yet recruiting, Marmara University

Additionally, SA strikingly downregulated the OVX-induced expression of osteoclast-specific genes and proteins. Taken together, this study elucidated that SA can effectively protect against osteoporosis by suppressing osteoclastogenesis via inhibition of the RANKL-RANK interaction, which supports the potential application of SA as a natural therapeutic agent for osteoporosis.

P4, N=50, Active, not recruiting, Massachusetts General Hospital | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

Denosumab has potential role for giant cell tumour of bone, it makes a less morbid surgery technically feasible. However, recurrence needs to be probed in long term follow up studies.

Mechanistic studies revealed that MM-derived CCL3 triggers the secretion of HMGB1 by osteocytes, a process required for osteocytic RANKL upregulation by MM cells. These findings identify a previously unknown CCL3-HMGB1 signaling axis in the MM tumor niche that drives bone resorption by promoting RANKL overproduction in osteocytes.

P4, N=63, Recruiting, Tuen Mun Hospital | Not yet recruiting --> Recruiting

Surgery was not possible due to comorbidities, so fulvestrant(500 mg/month)+denosumab(120 mg/month)was started. Furthermore, as the tumor markers were elevated, abemaciclib(300 mg/day)was added, which resulted in a decrease in the tumor markers...During the course of treatment, the tumor markers rose again, so the dose was increased to 250 mg/day, which resulted in a decrease in the tumor markers and good tolerability. At present, 36 months after the start of treatment, long SD has continued, no adverse events of grade 3 or higher have been observed, and the drug has been well tolerated.

We excluded those with a history of fragility fracture, multiple myeloma, Cushing's disease, primary hyperparathyroidism, osteomalacia, untreated vitamin D deficiency, secondary osteoporosis, or other systemic rheumatic diseases, as well as use of oral steroids for 2 or more weeks in the 6 months prior or current use of hormone replacement therapy, current oral bisphosphonate, past or current intravenous bisphosphonate, teriparatide, or denosumab therapies...This study of 30 patients with AxSpA found that abnormalities in bone density and microarchitecture at weightbearing sites were associated with longer disease duration. Because of its small sample size, larger studies are needed to better characterize the pathogenic disease factors that govern skeletal damage in AxSpA.

P4, N=36, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed

Treatment with bisphosphonates (P = 0.17) or denosumab (P = 0.75) had no significant effect on ROR2 expression. Patients with GCT exhibit more than twofold upregulation of ROR2 expression, confirming its role in causing osteoclast-mediated bone destruction. Therefore, ROR2 may be a target for drug development in the treatment of GCT.

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

Objective: By analyzing baseline and follow up data from RESCUE, we describe the current (neo)adjuvant treatment landscape for pt with ER+ HER2neg early-stage breast cancer including: type of endocrine agents used, addition of GnRH analogs (GnRHAa)/ovarian function suppression (OFS) to ET in premenopausal pt, use of chemotherapy and use of bone modifying agents (Bisphoshonates or Denosumab) in the adjuvant setting...In these 57 pt, GnRHa/OFS was recommended to be combined with an aromatase inhibitor as initial ET in 15 cases (3,8% of premenopausal pt) and with tamoxifen in 41 cases (10,4% of premenopausal pt)... These real world data show that in spite of existing guideline recommendations for the use of GnRHa/OFS in premenopausal women with early luminal breast cancer at higher risk for relapse, this is not routinely implemented. Therefore, regarding the ET recommendation, this patient cohort might be undertreated. Follow up data on actually received ET (including +/- GnRH) and CTX (including +/- anthracyclines) will be presented in detail.

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.