clodronate disodium / Generic mfg. - LARVOL DELTA

C-Mannosyl tryptophan dynamics in a mouse model of the peritoneal dissemination of ovarian cancer. (PubMed, J Biol Chem) - "C-Man-Trp levels in the plasma and peritoneal cavity cells of normal healthy mice were also suppressed by clodronate liposomes, whereas the expression of C-Man-Trp metabolism-related genes showed different changes from those in mice transplanted with HM-1 cells. Collectively, these results demonstrate that tumor-stimulated macrophages play a pivotal role in the dynamics of C-Man-Trp in mice with ovarian cancer."

Journal • Preclinical • Oncology • Ovarian Cancer • Solid Tumor • Targeted Protein Degradation • Transplantation • CCN1 • SPON1 • THBS1

Targeting NLRP3 inflammasome: a novel strategy for improving immune checkpoint inhibitor-associated pneumonitis. (PubMed, Transl Lung Cancer Res) - "Therapeutic interventions with NLRP3 inflammasome inhibitors (MCC950 and dapansutrile) and a macrophage-depleting agent (clodronate liposomes) were evaluated by micro-computed tomography (CT), histopathology, and serum inflammatory cytokine assays. The findings revealed: (I) significant upregulation of NLRP3 inflammasome pathway-related genes and downstream factors (IL-1β, IL-18) in CIP mouse lungs, alongside increased macrophage infiltration; (II) pneumonitis injury was markedly alleviated and serum inflammatory cytokine levels were reduced by both NLRP3 inflammasome inhibition and macrophage depletion; (III) dapansutrile downregulated NLRP3 expression via inhibition of the NF-κB pathway; (IV) enriched macrophage subpopulations (Mac-IL1B) expressing high levels of NLRP3 were identified in CIP patients. This study provides the first evidence that NLRP3 inflammasome activation constitutes a key upstream mechanism in CIP pathogenesis, offering novel therapeutic strategies..."

Checkpoint inhibition • IO biomarker • Journal • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • IL18 • IL1B • NLRP3

Prolonged Pig-to-baboon Lung Xenograft Survival with 11GE Pigs with HLA-E Expression and Donor Macrophage Depletion (ISHLT 2026) - "Pigs were pre-treated with liposomal clodronate (LC) to deplete lung macrophage and DDAVP for vWF depletion...2).Conclusion The 11GE lung xenograft with LC achieved a record 33-day survival associated with reduced early innate immune injury. We hypothesize that some combination of HLA-E, h*pvWF, avoiding the CMAHKO '4th antigen', along with donor lung macrophage depletion, may further extend lung xenograft survival."

Hematological Disorders • Thrombosis • CD20 • CXCL8 • HLA-E • IL6

The liver regulates ectopic calcification in Abcc6-deficient models of Pseudoxanthoma Elasticum. (PubMed, J Clin Invest) - "We show that ectopic calcification in PXE is primarily dystrophic and treatment with clodronate or etidronate, that prevent the growth of calcium hydroxyapatite mineralization, was sufficient to rescue the phenotype of ectopic cardiac calcification in Abcc6-deficient states. Taken together, these observations highlight the role of the liver in regulating target tissue metabolic and mitochondrial function in causing ectopic calcification in Abcc6-deficient states."

Journal • Cardiovascular • Genetic Disorders • Immunology • Metabolic Disorders • Rare Diseases • ABCC6

Local Administration of Clodronate, Simvastatin, and Hydroxyapatite in an Immature Piglet Model of Femoral Head Osteonecrosis for Legg-Calve Perthes Disease: A Pilot Study (AAOS 2026) - "While a combination of simvastatin and clodronate, even when combined with hydroxyapatite, may provide some protective effects, it does not prevent femoral head collapse. Further femoral heads have already been treated and harvested and are undergoing analysis. Our study reveals preliminary findings of our experimental investigation of different combinations of local pharmacological agents on an immature piglet model."

Clinical • Inflammation • Orthopedics

An IgG-Macrophage Axis Suppresses IgE-Mediated Itch (AAAAI 2026) - "An MC903-induced atopic dermatitis model examined efficacy against basophil-leukotriene-mediated itch...Mechanistic studies employed enzymatic Fc glycan removal, macrophage depletion using clodronate liposomes and anti-M-CSF antibodies, and behavioral scratching assessments...Conclusions The study establishes a unifying neuroimmune axis where protective IgG antibodies interrupt diverse IgE-driven itch circuits through FcγR activation on macrophages. This IgG-FcγR-macrophage pathway represents a promising therapeutic target, suggesting strategies to boost protective IgG responses or directly modulate activating FcγRs could provide durable relief for chronic pruritic disorders."

Atopic Dermatitis • Dermatitis • Immunology • CSF1

LncRNA Gm16023 ameliorates hyperglycemia-exacerbated septic intestinal injury by modulating macrophage polarization via miR-377-3p/Sirt1 axis. (PubMed, Mol Ther) - "Using both a genetic CD11b-DTR model and clodronate liposome (Cls)-mediated chemical ablation, we demonstrated that macrophage depletion markedly attenuated hyperglycemia-driven septic intestinal injury, underscoring their essential pathogenic role. To facilitate therapeutic delivery, we engineered a lipid nanoparticle (LNP)-encapsulated Gm16023 plasmid system that efficiently delivered lncRNA in vivo and conferred protection against intestinal injury in both in vitro and in vivo models. Collectively, our findings indicate that hyperglycemia promotes macrophage-mediated septic intestinal injury via the lncRNA Gm16023/miR-377-3p/Sirt1 axis, highlighting a potential RNA-based therapeutic strategy for diabetic sepsis."

Journal • Diabetes • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Septic Shock • ITGAM

Lidocaine suppresses lung cancer metastasis by inhibiting polarisation of tumour-associated macrophages in mice. (PubMed, Br J Anaesth) - "Our results indicate that lidocaine attenuates tumour metastasis through modulation of M2b-polarised TAMs in non-small cell lung cancer, providing a mechanistic basis for the potential application of anaesthetics in lung cancer patients."

Journal • Preclinical • Anesthesia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Vaccine-induced antibodies can limit Salmonella infection in the absence of complement or macrophages. (PubMed, mBio) - "Depletion of monocytic cells using clodronate liposomes demonstrated that these cells help prevent antigen dissemination...Additionally, we find that the classical complement cascade is not necessary for bacterial clearance but does facilitate bacterial capture by macrophages. Overall, our findings reveal that multiple antibody-mediated pathways operate in vivo, exhibiting some redundancy in their combined efforts to control infection, underscoring the importance of antibody functions in limiting bacterial spread."

Journal • Infectious Disease

Adverse effects of the PENTO(CLO) protocol in the prevention and management of iatrogenic head and neck bone necrosis in cancer patients: A systematic review and meta-analysis. (PubMed, Support Care Cancer) - "The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients."

Adverse events • Journal • Retrospective data • Review • Oncology

GM-CSF exacerbates pulmonary arterial hypertension via CCL2/CCR2-axis-mediated macrophage NLRP3 inflammasome activation. (PubMed, Int Immunopharmacol) - "Key interventions involved administering a GM-CSF neutralizing antibody, depleting macrophages with clodronate liposomes, and utilizing Ccr2-/- mice...This study confirms that endothelial cell-derived GM-CSF promotes macrophage-NLRP3 inflammasome via the CCL2/CCR2 axis, thereby driving the progression of PAH. This axis may represent a promising therapeutic target for PAH."

Journal • Cardiovascular • Hypertension • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CCL2 • CCR2 • CSF2 • NLRP3

Mesenchymal stromal cell administration promotes macrophage-mediated bile duct regeneration. (PubMed, Regen Ther) - "An experimental system was also developed in which clodronate liposomes were administered alongside MSCs to eliminate the influence of macrophages...Macrophages play a crucial role in bile duct regeneration, and MSC administration has regenerative effects. This approach has potential as a novel treatment modality for bile duct injuries."

Journal • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis • CK19 • KRT19 • SOX9

PPARα-NFκB heterodimer mediates obesity-induced diastolic dysfunction through autocrine production of IL-6. (PubMed, J Clin Invest) - "HFD consumption directly stimulated IL-6 production in cardiomyocytes before local inflammation developed and induced diastolic dysfunction even in the presence of macrophage depletion with clodronate in the heart...HFD-induced diastolic dysfunction was attenuated by cardiac-specific deletion of either Ppara or Il6, as well as by interference with the PPARα-NFκB heterodimer formation by a molecular decoy. These results suggest that elevated FFAs directly upregulate Il6 through the PPARα-NFκB heterodimer in cardiomyocytes and highlight autocrine production of IL-6 as a key downstream mechanism in the initial development of diastolic dysfunction."

Journal • Cardiomyopathy • Cardiovascular • Genetic Disorders • Inflammation • Obesity • IL6 • PPARA

Macrophage Depletion by Intracerebroventricular Administration of Clodronate-Liposome Attenuates the Development of Angiotensin II-Salt-Induced Neurogenic Hypertension in Rats. (PubMed, JMA J) - "Intracerebroventricular injection of clodronate-liposome attenuated the angiotensin II-salt-induced increases in the depressor response, gene expressions, and cell number. Our data suggest that macrophages in the CSF are involved in the development of angiotensin II-salt-induced neurogenic hypertension by modulating brain inflammation."

Journal • Preclinical • Cardiovascular • Hypertension • Inflammation • IL6

Accumulation of free nuclei denotes defective phagocytic capacity of macrophages and occurs after infection with Listeria monocytogenes and lymphocytic choriomeningitis virus. (PubMed, Front Immunol) - "This was associated with lethal outcome and occurrence of acute hepatopathy in these mice after Listeria monocytogenes infection. Our findings highlight a simple and noninvasive method to assess macrophage phagocytic function in vivo, which should be assessed in further murine and human studies as a tool for predicting host vulnerability to infection."

Journal • CNS Disorders • Hepatology • Infectious Disease • IFNG

Selective Depletion of Tumor-Associated Macrophages with Biomineralized Erythrocyte Nanoghosts to Boost Neoadjuvant Radioimmunotherapy. (PubMed, ACS Nano) - "Functioning as a universal TAM-targeting carrier, SBC@CaP can be modularly loaded with agents, such as disodium clodronate to induce apoptosis or ferrous ions to trigger ferroptosis in TAMs...This modular strategy enables precise TAMs clearance, TME remodeling, and immune activation. In multiple tumor models, SBC@CaP effectively reprograms the immune landscape and suppresses tumor progression, offering a versatile platform to mitigate the drawbacks of NRT and potentiate macrophage-targeted cancer therapy."

Journal • Oncology

Loss of mechanical stress induces synovitis, fibrosis and articular cartilage degeneration via distinct synovial cell subsets. (PubMed, Sci Rep) - "Histological examination showed that MMS initially induced macrophage proliferation, while macrophage depletion by intra-articular administration of clodronate liposomes inhibited MMS-induced synovitis, fibrosis and cartilage degeneration, accompanied by a marked reduction in the MMS-distinct subsets. Our findings identified MMS-induced alterations in synovial cells and their roles in joint phenotype, suggesting that joint motion and mechanical loading contribute to the regulation of joint homeostasis."

Journal • Fibrosis • Immunology • LRRC1 • MMP9

Intraperitoneal clodronate liposomes remodel the local macrophage niche and potentiate biomaterial-induced osteoinduction. (PubMed, Mol Biol Rep) - No abstract available

Journal • Immunology

A novel approach for discriminating lipophilic bisphosphonate-based pharmaceuticals using a potentiometric array. (PubMed, Anal Methods) - "The lipophilicity of bisphosphonates including ibandronate, clodronate, risedronate, and alendronate was analyzed in both standard and commercial samples. The influence of membrane composition (presence or absence of an anion-exchanger) and PANI deposition conditions (monomer form and/or salt content) on membrane surface properties (lipophilicity and signal stability) was investigated and confirmed using surface-wetting characterization, SEM-EDS mapping and potentiometry. Principal component analysis (PCA) enabled discrimination among the bisphosphonates based on their lipophilicity and revealed distinct contributions of individual ISMs in both standard and commercial samples."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Osteoporosis • Rare Diseases • Rheumatology

Perivascular macrophage depletion impairs glymphatic clearance and amplifies cortical hyperexcitability: Preclinical insights with clinical validation. (PubMed, J Cereb Blood Flow Metab) - "Using clodronate liposomes (CLOs), we achieved >85% PVM depletion in mice. Following pentylenetetrazole (PTZ) challenge, PVM-depleted mice exhibited anxiety-like behaviors (reduced center time, p < 0.05), impaired working memory (decreased spontaneous alternation, p < 0.05), and increased cortical hyperexcitability, including shorter seizure latency and elevated EEG total power (p < 0.05)...These results highlight PVMs as essential modulators of the glymphatic-metabolic axis, linking vascular health to brain excitability. Targeting the PVM-GS interface offers therapeutic potential for disorders involving vascular dysfunction and neuronal hyperexcitability."

Journal • Preclinical • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry

Macrophage Niche Reconstitution Reveals Dynamic Transcriptional and Communication Networks Renal Macrophage-Epithelial Communication. (PubMed, Res Sq) - "Integrated transcriptomic, pathway, transcription factor, and cell-cell communication analyses were combined with functional validation using clodronate-mediated macrophage depletion in Spp1 (Opn)-deficient mice...Conclusion Our study defines RM regeneration as a transcriptionally regulated, communication-driven process orchestrated by epithelial-derived chemokines, macrophage metabolic reprogramming, and subtype-specific signaling networks. These findings revealed a hierarchical macrophage-epithelial communication program coordinating RM niche restoration and tubular repair."

Journal • CX3CL1 • SPP1

Vesicular nucleotide transporter (VNUT)-dependent ATP secretion by hepatic stellate cells promotes liver fibrosis. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "Thapsigargin, an inducer of endoplasmic reticulum Ca2+ release, upregulated VNUT expression, suggesting a transcriptional regulation of VNUT-dependent ATP release by Ca2+ signaling. Clodronate treatment reduced CD41-positive platelets in liver tissue. These findings highlight VNUT-mediated ATP secretion as a key regulator of HSC function and a potential therapeutic target for liver fibrosis."

Journal • Fibrosis • Immunology • Liver Cirrhosis • AMPK • ITGA2B • TGFB1 • VAMP7

Experimental study of tumor-associated macrophage-derived SPP1 inhibit CD8+ T cells to promote Colorectal cancer progression. (PubMed, Neoplasia) - "In a macrophage-depleted murine CRC model established with clodronate (CL2MDP) liposomes and MC38 cells, macrophage depletion significantly inhibited tumor growth, accompanied by reduced SPP1 expression and increased infiltration of CD8⁺ T cells and type 1 cytotoxic T (Tc1) cells...These effects were attenuated by SPP1 neutralization or CD44 inhibition. Collectively, these findings elucidated TAM-derived SPP1 as a key mediator of immune suppression in CRC and suggested that the TAM-SPP1 axis is a potential therapeutic target."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CD8 • IFNG • SPP1 • TNFA • ZAP70

High-dimensional phenotyping reveals novel macrophage-like and hybrid subsets within murine splenic conventional dendritic cells. (PubMed, PLoS One) - "This study employed multi-parametric flow cytometry and clodronate liposome (CL) depletion to systematically re-evaluate splenic CD11chighMHCIIhigh cDCs in C57BL/6 mice...These findings demonstrate unprecedented cDC plasticity driven by microenvironmental signals, revising conventional classification frameworks and proposing new targets for DC-based immunotherapies in autoimmunity and cancer. Our phenotypic mapping provides a foundational framework for future functional investigations into these novel subsets."

Journal • Preclinical • Oncology • CCR2 • CD4 • CDK1 • CX3CR1 • ITGAX • MERTK

Monocyte depletion reduces late experimental post-thrombotic fibrotic injury in a stasis mouse model. (PubMed, Thromb Res) - "Mo/MØ direct the post VT late fibrotic response, possibly by affecting fibroblasts and inflammatory cytokine expression. This effect was only found with the complete stasis model and is consistent with worsened PTS in humans with complete venous obstruction."

Journal • Preclinical • Cardiovascular • Fibrosis • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Thrombosis • DDR2 • IL6 • ITGAM • VEGFA