P=N/A, N=218, Not yet recruiting, Huazhong University of Science and Technology Union Shenzhen Hospital; Huazhong University of Science and Technology Union Shenzhen Hospital

P1, N=22, Recruiting, University of Wisconsin, Madison | Suspended --> Recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

This study concludes with evidence that E2 decreases osteoclast maturation and bone resorption through the regulation of multiple signalling pathways, thereby exhibiting an osteoprotective role in OVX mice. Consequently, E2 exhibits significant potential as a prospective drug candidate for treating osteoporosis.

Indocyanine green (ICG) as a photothermal-transducer ablated tumor cells, zoledronic acid (ZA) depletes TAMs recruited by the inflammatory tumor microenvironment (mostly M2-like phenotype), SB-505124 affects CAFs proliferation in the tumor microenvironment (TME) by inhibiting the transforming growth factor-β （TGF-β） pathway, thereby removing physical barriers to T cell infiltration. In a breast cancer model, these immunomodulatory nanoliposomes markedly decrease the population of M2-like TAMs in the TME, eliminate physical barriers hindering T cell infiltration, reshape the inflammatory immune-suppressive tumor microenvironment, eventually leading to a rate of tumor eradication of 94%. This multifunctional ICG-SB@Lip-ZA nanosystem (including photothermal conversion, TAM depletion, and TGF-β pathway blockade) offers a promising strategy for mitigating the deteriorating tumor microenvironment following PTT and presents a more efficient approach for clinical photothermal-immune combination therapy.

Data on the use of zoledronic acid (ZA) in juvenile CRMO are scarce...The patient's condition stayed stable while taking naproxen (20 mg/kg/day) and methotrexate (10 mg/week) for 1.5 years until he experienced right elbow pain, swelling, no overlying skin erythema, and a restricted range of motion...Non-steroidal anti-inflammatory drugs and methotrexate were initially effective in treating our patient's condition, but a recurrence necessitated treatment modification. To the best of our knowledge, this case is the first documented instance of the use of ZA in CRMO in Iraq and Arab nations.

CGD exerts a significant anti-osteolytic activity both in vitro and in vivo by inhibiting RANKL-induced osteoclastogenesis and function. Consequently, our study indicated that CGD may have a potential therapeutic role in the precaution of osteolytic bone disease.

P1, N=22, Suspended, University of Wisconsin, Madison | Recruiting --> Suspended

P3, N=120, Recruiting, St. Louis University | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026

RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy.

P1/2, N=27, Not yet recruiting, University of Florida

Finally, molecular docking indicated that STAT6 is a target of Zoledronic Acid, which can delay UM tumorigenicity by inhibiting STAT6 expression. Taken together, our results indicate that the STAT6/LINC01637 axis promotes UM progression via autophagy and may serve as a potential therapeutic target for UM.

P=N/A, N=140, Completed, Second Affiliated Hospital, School of Medicine, Zhejiang University

While the suppressive effect of zoledronate (Zol) on cell viability and migration was observed, the addition of EMD significantly mitigated this effect and enhanced cell viability and migration...This finding suggests that EMD could mitigate the effects of BPs, resulting in the recovery of cell survival, migration, and gene and protein expression. However, the behavior of the osteoblasts was not fully restored, and further studies are necessary to confirm their effects at the cellular level and to assess their clinical usefulness in vivo for the prevention and treatment of MRONJ.

P1/2, N=12, Recruiting, DexTech Medical AB

P4, N=350, Active, not recruiting, University of Edinburgh | Recruiting --> Active, not recruiting | Trial completion date: Apr 2023 --> Jul 2025 | Trial primary completion date: Dec 2022 --> Feb 2025

P=N/A, N=60, Not yet recruiting, The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine; The Third Affiliated Hospital of Guangzhou University of Tradit

This nanodevice is composed of a dual-pore mesoporous silica core with the capacity to house small cytotoxic drugs, such as doxorubicin or zoledronic acid, and large macromolecules, such as glucose oxidase. Once there, the nanoassemblies also exhibited excellent capacity to induce potent macrophage depletion. This strategy can be directly adapted for the treatment of different malignancies due to the modular nature of the nanoplatform, which can be loaded with different therapeutic agent combinations and pave the way for the development of personalized nanomedicines for diverse types of tumors.

Importantly, the in vivo studies and ki67 and GPX4 staining of tumor sections demonstrated that the ZA@HMNs efficiently accumulated in 4T1 tumors to hinder tumor growth via ZA chemotherapy combined with OH-mediated ferroptosis. This work presents a practicable strategy to fabricate ZA@HMNs for breast tumor-targeted chemo/chemodynamic therapy with potential clinical translation.

Evidence of actual tumor cell elimination, although not significant, was only obtained after preincubation of Mel-RhS with pamidronate, a phosphoantigen-inducing agent, indicating the need for additional T cell receptor-mediated signaling for Vγ9Vδ2-T cells to reach their full oncolytic potential. This study highlights the viability and persistence of Vγ9Vδ2-T cells within the 3D microenvironment, their migratory and antitumor functionality, and the suitability of the model for testing T cell-based therapies, contributing both to the understanding of Vγ9Vδ2-T cell biology and their application in cancer immunotherapy.

The KATP channels are effective in the M1 AQP4-tetramer and M23 AQP4-OAP cells. Zoledronic acid can be effective in targeting pathogenic M1 AQP4-tetramer cell phenotypes inhibiting KATP channels and inducing early apoptosis.

P2, N=55, Completed, DexTech Medical AB | Unknown status --> Completed

This study aims to utilize EVs for OS management by co-delivering Hdac1 siRNA and zoledronic acid (zol)...Furthermore, EVs were used as the carrier for co-loading drug (zol) and small RNA (Hdac-1). This approach of using surface engineered EVs as carriers for cargo loading and delivery can be a promising strategy for osteosarcoma management.

Trifolirhizin can effectively inhibit osteoclast production and bone resorption activity. The results of our study provide evidence for trifolirhizin as a potential drug for the prevention and treatment of osteoporosis and other osteolytic diseases.

No abstract available

In conclusion, ZA preserved renal function and prevented renal fibrosis in a rat model. These were achieved through targeting protein prenylation mainly by inhibiting FPPS.

This work suggests that TFEB is a gatekeeper of the sensitivity to chemotherapy and immuno-killing in NSCLC, and that the TFEBlowABCA1lowABCC1high phenotype can be predictive of poor response to chemotherapy and immunotherapy. By reshaping both cancer metabolism and tumor immune-microenvironment, zoledronic acid can re-sensitize TFEBlow NSCLCs, highly resistant to chemo- and immunotherapy.

Using Tg(drl:hoxa9) embryos, we performed chemical screening and identified four FDA-approved drugs, ethacrynic acid, khellin, oxcarbazepine, and alendronate, that efficiently restored myeloid differentiation. Thus, the combination of ethacrynic acid and ATRA may have broader clinical applications. In conclusion, through zebrafish-aided screening, our study identified four drugs that can be repurposed to induce AML differentiation, thus providing new agents for AML therapy.

P2, N=24, Recruiting, University of California, Davis | Not yet recruiting --> Recruiting | Trial completion date: Jul 2025 --> Jun 2026 | Initiation date: Mar 2024 --> Sep 2024 | Trial primary completion date: Feb 2025 --> Dec 2025

Herein, multifunctional self-assembled supramolecular fiber hydrogels (Ce-Aln gel) consisting of alendronate (Aln) and cerium (Ce) ions were constructed for osteoporotic bone defect repair...In vivo experiments showed that the clinical drug-based Ce-Aln gel effectively promoted the tissue repair of osteoporotic bone defects by improving inflammation and inhibiting osteoclast formation at the defect. Notably, in vivo systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects.

No abstract available

Neurons treated with CM from irradiated osteoclasts showed increased expression of pain-associated neuropeptides CGRP and Substance P, which was mitigated by osteoprotegerin and risedronate. This study suggests that high-dose radiation enhances osteoclast activity, upregulating pain-associated neuropeptides in sensory neurons, and that inhibitors like osteoprotegerin and risedronate may offer therapeutic strategies for managing radiation-induced pain.

P=N/A, N=2881, Completed, Daewoong Pharmaceutical Co. LTD. | Recruiting --> Completed

Collectively, our findings provide evidence that ketotifen-induced TME reprograming can improve the efficacy of nanomedicine-based chemoimmunotherapy in sarcomas.

P=N/A, N=60, Completed, Cairo University | Not yet recruiting --> Completed | Trial completion date: Dec 2024 --> Jun 2024 | Trial primary completion date: Dec 2024 --> May 2024

Adult women with HER2-positive breast cancer amendable to curative surgery who consented to the study received four cycles of ZA at 4 mg + doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 followed by four cycles of ZA at 4 mg + docetaxel 100 mg/m2 + trastuzumab 6 mg/kg (8 mg/kg as a loading dose), all in a 21 days-cycle, totalizing 8 cycles before surgery. ZA plus neoadjuvant therapy in HER2-positive breast cancer shows provoking survival outcomes. Clinical and pre-clinical investigation with dual anti-HER2 blockage is warranted.

P1, N=1, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Feb 2025 --> May 2024 | Trial primary completion date: Feb 2025 --> May 2024

Ex-vivo hemocompatibility and in-vivo biocompatibility of Aln/Lf/IVM-NLC (1 mg/mL) were established, with pronounced amelioration of hepatic and renal toxicity compared to higher Aln doses. The innovative Aln/Lf/IVM-NLC could serve as a promising nanovector for bone-homing, active-targeted leukemia therapy.

Mechanistically, RNAi-mediated silencing of IRF7 and IFIT3 in OC precursors impair the suppressive effect of the IFN-I inducers on OC differentiation. Taken together, these results demonstrate that IFN-I inducers play a protective role in bone turnover by limiting osteoclastogenesis and bone resorption through the induction of OC-specific mediators via the IFN-β signaling pathway.

Moreover, stIL15-OPS-γδ T cells were efficacious against patient-derived osteosarcomas in animal models and in vitro, where efficacy could be boosted with the addition of zoledronic acid. Together, the data identify stIL15-OPS-γδ T cells as a candidate allogeneic cell therapy platform combining direct cytolysis with bystander activation to promote tumor control.

Here, a calcium carbonate (CaCO3)/polydopamine (PDA)-based nanosystem (A-NPs@(SHK+Ce6)) was developed for the targeted codelivery of the photosensitizer Ce6 and shikonin (SHK) to OS tumours via the bone-targeting ability of alendronate sodium (ALN)...Importantly, A-NPs@(SHK+Ce6), in combination with programmed cell death protein 1 (PD-1) checkpoint blockade, showed a remarkable ability to eliminate distant tumours and promote long-term immune memory function to protect against rechallenged tumours. This work presents a novel multiple-component combination strategy that coregulates the acidic TME and TAM polarization to reprogram the TIME.

P2, N=60, Completed, Columbia University | Recruiting --> Completed

P=N/A, N=500, Recruiting, Fudan University