Furthermore, Ps-GOS markedly inhibited RANK expression, which serves as an initial transmitter of many osteoclastogenesis-related cascades and inhibited proteolytic enzymes, including TRAP, matrix metallopeptidase 9 (MMP-9) and cathepsin K (CTK). These findings indicate that Ps-GOS could potentially be beneficial as an effective natural agent for bone metabolic disease.

RANKL and IL-6 expressions in response to orthodontic forces and in the control were clearly inhibited by Shh inhibitor RU-SKI 43. Shh did not directly link to RANKL and IL-6 for root and bone resorptions by orthodontic force but was associated with cell activities to be finally guided by the production of cytokines in hPDL cells.

P3, N=392, Active, not recruiting, Luye Pharma Group Ltd. | Recruiting --> Active, not recruiting

P3, N=595, Terminated, ETOP IBCSG Partners Foundation | Completed --> Terminated; Completion of recruitment was not feasible as accrual was slower than anticipated. Even if a benefit for denosumab could be shown, these results would be of very limited clinical impact by the time they would be available

P4, N=101, Completed, National Taiwan University Hospital | Recruiting --> Completed | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Jul 2023

P1, N=190, Completed, Biocon Biologics UK Ltd | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> Oct 2023 | Trial primary completion date: Feb 2024 --> Oct 2023

P1/2, N=72, Completed, Peter MacCallum Cancer Centre | Active, not recruiting --> Completed

P1, N=132, Recruiting, Taizhou Mabtech Pharmaceutical Co.,Ltd

P1, N=209, Completed, Alvotech Swiss AG | Active, not recruiting --> Completed

P1, N=0, Withdrawn, Taizhou Mabtech Pharmaceutical Co.,Ltd | N=252 --> 0 | Not yet recruiting --> Withdrawn

Dau prevents OVX-induced bone loss by inhibiting osteoclast activity and bone resorption, potentially offering a new approach for preventing and treating metabolic bone diseases such as osteoporosis. This study provides innovative insights into the inhibitory effects of Dau in an in vivo OVX model and elucidates the underlying mechanism.

The presence of BoM is a negative prognostic factor for NSCLC patients with an EGFR mutation, possibly due to the presence of extrathoracic metastases. However, adding AAT and denosumab, along with sequential osimertinib, to the treatment regimen for patients with BoM can improve survival outcomes.

We confirmed the expression of osteoclast-related proteins in the mouse middle ear. These results imply that air pollutants might affect RANKL/RANK signaling, which is associated with bone remodeling.

P3, N=278, Recruiting, Shanghai Biomabs Pharmaceutical Co., Ltd. | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

P4, N=100, Not yet recruiting, Amgen

P3, N=1380, Active, not recruiting, Swiss Group for Clinical Cancer Research | Recruiting --> Active, not recruiting

P=N/A, N=100, Recruiting, University of Colorado, Denver | Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2025

P1, N=252, Completed, Shanghai Henlius Biotech | Recruiting --> Completed

P3, N=478, Not yet recruiting, RenJi Hospital

P4, N=5, Terminated, James J. Peters Veterans Affairs Medical Center | N=32 --> 5 | Recruiting --> Terminated; Study ended early due to COVID-19

P1, N=225, Not yet recruiting, Xentria, Inc.

Denosumab in combination with dual ICI modulates cytokine expression and T-cell composition in peripheral blood. The upregulation of CXCL-13, a key factor for initiating tertiary lymphoid structures, strengthens the hypothesis that denosumab indeed boost immunological effects.

P=N/A, N=60, Recruiting, Peking University People's Hospital

ZA once every 12 weeks is the cost-effective treatment option for BC with bone metastases in India. The present study findings hold significance for standard treatment guidelines under India's government-funded health insurance program.

P4, N=40, Active, not recruiting, James J. Peters Veterans Affairs Medical Center | Recruiting --> Active, not recruiting

Based on these clinical and pathological findings, the patient was diagnosed with hypercalcaemia and leukocytosis associated with malignancy and was treated with denosumab...Therefore, chemotherapy was discontinued. One week after the chemotherapy was discontinued, the patient died of respiratory failure.

Subsequently, FME was found to effectively suppress RANKL-induced osteoclast differentiation compared with that by the non-fermented mealworm extract. These findings suggest that FME may confer anti-osteoclastogenic effects, providing insights into its potential application in treatment of osteoporosis.

The patient suspended Denosumab for more than six months before teeth extraction for MRONJ prevention; hence, failure to discontinue Osimertinib led us to consider it a possible etiological factor. From a literature analysis, only one case has already been published reporting a possible Osimertinib-related occurrence of MRONJ in lung cancer patients. Our case is a further report that could be intended as an alert both for oncologists and dentists to share decisions about the oral management of such patients together, also informing them about this possible risk. Also, this report could trigger in the scientific community the necessity to evaluate further guidelines for similar doubtful cases in which the drug interaction, the mono-suspension, and the possible removable prosthesis-related additional trauma should be considered causes or con-causes.

The diagnostic sensitivity and specificity of H3.3 G34W for GCTB were 88.1% and 100%, respectively. This constitutes one of the first reports from our country, further validating the diagnostic value of H3.3 G34W in differentiating GCTB, including metastatic and malignant forms from its mimics, including small biopsy samples. Its value in various diagnostic dilemmas is presented and utility in identifying residual tumor cells in post-denosumab treated GCTBs is worth exploring.

P4, N=340, Not yet recruiting, Yonsei University

Our results suggest that the RANK/RANKL axis may serve as a potential tumor marker and promising therapeutic target for OS metastasis. Furthermore, DMF may have clinical applications in the treatment of lung metastasis in patients with OS.

P4, N=100, Recruiting, Xi'an Honghui Hospital | Not yet recruiting --> Recruiting

P3, N=479, Completed, Celltrion | Active, not recruiting --> Completed

Additionally, we proved that changes in DNA methylation contribute to upregulating the expression of RANKL and downregulating the expression of OPG, which are critical for bone homeostasis and GCTB development. Our results suggest that the overexpression of RANKL/RUNX2 and the lower expression of OPG are associated with recurrence in GCTB patients.

P2, N=20, Active, not recruiting, University of Rochester | Trial completion date: Jun 2024 --> Jun 2025

Our study demonstrates that melittin has the ability to inhibit the NF-kB pathway in a rat model, attenuate the inflammatory response associated with periprosthetic osteolysis, and reduce the impact of RANKL/OPG, thereby delaying osteoclast activity and alleviating periprosthetic osteolysis.

P2, N=27, Completed, Columbia University | Active, not recruiting --> Completed

We also saw broad induction of CTLA-4 and TIM3 expression in circulating lymphocytes and some monocyte populations. These findings suggest that denosumab treatment by itself has modest immunomodulatory effects, but when combined with conventional cancer treatments, can lead to the induction of immunologic checkpoints.

The results suggest that MZF1 may be involved in osteoclast differentiation by regulating RANKL-induced ferroptosis of osteoclasts. Collectively, our findings shed light on the essential involvement of MZF1 in the regulation of osteoclastogenesis in osteoporosis and provide insights into its potential underlying mechanism.

P3, N=1360, Not yet recruiting, Shanghai JMT-Bio Inc.

P2, N=56, Completed, Children's Oncology Group | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Dec 2023

We identified a new differentiation stage of osteoclast maturation, intermediate cell, by comparing histological findings before and after denosumab treatment. We demonstrated that discrepancies exist between histological and molecular data and highlight the need for establishing an integrated definition of osteoclasts considering morphology and marker expression.