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clodronate disodium (Bonefos / Clastoban)

✓ Approved

Takeda · SLC17A9 · Small Molecule

What is clodronate disodium?

clodronate disodium is a small molecule developed by Takeda. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesBonefos, Clastoban
CompanyTakeda
Drug ClassSmall Molecule
Molecular TargetSLC17A9
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Takeda

Mechanism of Action

Molecular Targets

clodronate disodium acts on 1 molecular target:

SLC17A9solute carrier family 17 member 9 (POROK8, VNUT)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

clodronate disodium is developed for 2 unique indications across 2 therapeutic areas.

Therapeutic AreaConditionPhase
Endocrine disordersHypercalcaemia of malignancy✓ Approved
Musculoskeletal and connective tissue disordersOsteoporosis✓ Approved

Related Research Articles

PubMedBrain, behavior, and immunity2026-08-30

Spatial synaptic pruning mechanism of NAC microglia in differential regulation of PTSD- and depression-like behaviors.

Zhao Mingyue M, Tian Wenyu W, Hu Xinyu X, Dai Jiajie J et al.

Post-traumatic stress disorder (PTSD) comorbid with depression is a prevalent, treatment-refractory clinical syndrome. Emerging evidence indicates shared microglial alterations in PTSD and depression, suggesting it may represent a common pathological substrate. However, the underlying neuroimmune mechanisms remain unclear. PTSD- and depression-like behaviors were induced in rats by using single prolonged stress combined with foot shock (SPS&S). Cellular activity, spatial distribution, and morphology were assessed using qPCR, immunofluorescence, and Golgi-Cox staining. Microglial activity was inhibited using clodronate liposomes (CDSlip) and minocycline. Bulk RNA sequencing was performed to profile neuroimmune-related signaling molecules. Stress induced PTSD- and depression-like behaviors, accompanied by region-specific enhanced microglial activity in the anterior-medial NAC core (amNACc) and lateral NAC shell (LNACsh). Selective depletion of microglia in amNACc and LNACsh via CDSlip specifically alleviated stress induced PTSD- and depression-like behaviors, respectively. Morphological and functional analyses in each region revealed that microglia reshaped the spatial pattern of neuronal structure and function, manifested by enhanced in amNAC and inhibited in LNACsh, via differentially pruning adjacent inhibitory synapses in corresponding region. Further transcriptomic analysis of synaptic pruning relevant signaling pathway showed upregulated expression of "Eat me" signal molecules (particularly Mertk) in the amNAC and downregulated expression of "Find me" signal molecules (particularly Cx3cr1) in the LNACsh, consistent with the observed spatial synaptic pruning profiles. Minocycline administration reversed stress-induced PTSD and depression-like behaviors while normalizing the region-specific alterations in synaptic pruning signaling molecules. Stress may elicit two regionally heterogeneous microglial subpopulations within NAC: phagocytosis-enhanced and recognition-impaired, which remodel the structure and function of local neural networks by differential pruning of inhibitory synapses, thereby driving the manifestation of PTSD- and depression-like behaviors, separately. These findings deepen our understanding of the neuroinflammatory mechanisms underlying trauma-related psychiatric disorders and identify novel targets for immunomodulation-based targets for transdiagnostic interventions .

PMID 42669315
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PubMedJournal of dental research2026-08-28

Macrophages Promote Vascular Maturation to Support Tooth Germ Morphogenesis.

Wang Z Z, Wang M M, Zhang R R, Wang J J et al.

Macrophages are increasingly recognized as key regulators of organogenesis, yet their contributions to tooth germ development remain poorly understood. Here, we integrated analysis of publicly available single-cell RNA sequencing datasets with multiplex immunohistochemistry to investigate the presence, distribution, and activation states of macrophages during tooth development. Macrophages were enriched in the dental follicle and dental papilla, expanded through local proliferation, and displayed a predominant tissue-resident macrophage (TRM)-like and M2-like phenotype. Spatial and transcriptomic analyses further revealed that macrophages preferentially localized adjacent to developing blood vessels and established a localized provascular niche enriched for vascular regulatory signaling pathways. Functional depletion of macrophages, both in vivo using Cx3cr1-dependent DTA mice and ex vivo with clodronate liposomes, impaired tooth germ growth and morphogenetic progression, accompanied by reduced tooth germ size, abnormal cusp morphology, increased apoptosis, and impaired vascular maturation. Notably, macrophage depletion reduced vascular maturation without markedly affecting overall vascular density. Given the well-established requirement for vascular maturation in tooth development and the close spatial association between macrophages and developing vessels, we examined whether macrophages contribute to the immune-vascular interactions required for morphogenesis. Macrophages expressed multiple vascular regulatory factors, including VEGFA, TGF-β, and IL1B, while inhibition of vascular maturation phenocopied the developmental abnormalities caused by macrophage depletion and was associated with attenuated bone morphogenetic protein-associated signaling. Together, these findings identify macrophages as important upstream regulators of tooth germ morphogenesis, acting in part by modulating vascular maturation, and provide new insights into immune-vascular crosstalk during tooth development.

PMID 42661281
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PubMedPathogens (Basel, Switzerland)2026-08-27

The Role of Macrophages in the Immune Response to Peritoneal Infection with Dirofilaria immitis Larvae in the Mongolian Gerbil (Meriones unguiculatus).

Campbell Elyssa E, Pope Catherine C, Greenway Katelin K, Garner Bridget B et al.

The host cellular mechanisms determining whether Dirofilaria immitis (canine heartworm) larvae establish infection remain poorly understood. The Mongolian gerbil (Meriones unguiculatus), a naturally nonpermissive host, mounts a rapid macrophage-dominated peritoneal cellular response to intraperitoneal (IP) larval challenge. To test whether macrophages mediate larval clearance, peritoneal macrophages were selectively depleted with IP clodronate liposomes (100 µL/10 g body weight; days -4 and -1 relative to infection) before challenge with approximately 40 D. immitis third-stage larvae (L3). A rat anti-mouse anti-F4/80 antibody was validated as a cross-reactive macrophage marker in jird peritoneal exudate cells (PECs) by standard and imaging flow cytometry, and depletion efficacy was confirmed prior to infection. Significantly more L3 were recovered from macrophage-depleted jirds (mean = 17.7%; SEM = 6.0%) than from PBS liposome controls (mean = 3.8%; SEM = 1.9%) at 1-day post-infection (p < 0.03). Cytology and flow cytometry confirmed near-complete macrophage depletion, and a significant compensatory neutrophilia was observed in depleted animals (64.5% ± 5.7% vs. 19.6% ± 5.1% in controls; p < 0.0001). These findings establish peritoneal macrophages as the primary innate cellular mediators of D. immitis L3 clearance in a nonpermissive host, providing a validated in vivo framework for mechanistic dissection of filarial host specificity.

PMID 42654787
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PubMedEnvironmental toxicology and pharmacology2026-08-26

Short-term renal findings during CaNa₂EDTA chelation in workers with occupational lead exposure: Proteinuria, albuminuria, and renal function changes.

Akkale Tuğba T, Başkara Çiğdem Ç

Occupational lead exposure may cause renal toxicity; however, the renal effects of calcium disodium ethylenediaminetetraacetic acid (CaNa₂EDTA) chelation therapy remain unclear. This study evaluated short-term renal function changes and urinary findings in workers undergoing CaNa₂EDTA chelation for occupational lead exposure. This retrospective study included 245 male workers with occupational lead exposure who received CaNa₂EDTA chelation therapy between January 2022 and January 2026. Urinary protein, albumin, and 24-hour urinary lead excretion were assessed on day 3, while post-treatment blood lead levels and renal function parameters were assessed on day 6. Blood lead levels significantly decreased after chelation therapy (p < 0.001). Urea levels decreased, whereas serum creatinine levels increased slightly and eGFR values declined significantly (all p < 0.001). Proteinuria and albuminuria were detected in 40.8% and 28.2% of patients, respectively. Employment in other occupational sectors was associated with higher odds of proteinuria, but not albuminuria, after adjustment. CaNa₂EDTA effectively reduced blood lead levels, while small changes in renal function and urinary abnormalities were observed during treatment; however, these findings cannot be attributed specifically to chelation therapy.

PMID 42648389
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PubMedToxics2026-08-26

Influence of Chelator Type on the Efficiency and Mechanisms of Electrokinetic Remediation of Copper- and Lead-Contaminated Loess.

Jin Yunxiao Y, Luo Longping L, Zhang Shixu S, Yuan Zheng Z

With the continued advancement of industrialization and urbanization in northwestern China, heavy metal contamination of loess sites has become an increasingly serious environmental issue. Heavy metals such as copper (Cu) and lead (Pb) are toxic, persistent, and readily retained by the mineral-pore framework of loess, which makes remediation difficult and threatens regional ecological security and human health. This study investigated electrokinetic (EK) remediation of artificially prepared loess co-contaminated with Cu and Pb using tartaric acid (TA), citric acid (CA), and disodium ethylenediaminetetraacetate (EDTA) as catholytes. Cu was generally removed more effectively than Pb because Pb was less adsorbed and immobilized more strongly. All three chelators enhanced metal desorption and migration through complexation, particularly in the cathode-side section. EDTA produced the greatest enhancement because it formed stable, negatively charged complexes with Cu and Pb over a broad pH range. Relative to the deionized-water control, EDTA increased the overall removal efficiencies of Cu and Pb to 55.4% and 27.2%, respectively, and promoted their transfer from the soil to the anolyte. These findings demonstrate that chelator-assisted EK treatment, particularly with EDTA, can effectively improve Cu and Pb removal from loess, while field application requires control of energy use, residual chelator, and post-treatment metal mobility.

PMID 42646940
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PubMedFrontiers in tuberculosis2026-08-25

Differential roles of resident lung macrophages during control of murine alveolar and airway Mycobacterium abscessus infection.

Haist Kelsey C KC, Congel Jack H JH, Corley Jodi M JM, Ochoa Alma E AE et al.

Mycobacterium abscessus (Mabsc), a nontuberculous mycobacterium (NTM), is readily cleared from healthy lungs but can cause infections in immunocompromised individuals and individuals with chronic airways diseases that disrupt mucociliary clearance, such as cystic fibrosis and bronchiectasis. In bronchiectatic airways, Mabsc can persist despite robust immune cell recruitment, raising the possibility that, in addition to impaired mucociliary clearance, local pulmonary immune defects contribute to NTM susceptibility. Since chronic infections result from failed eradication of acute infection, we sought to determine whether immune cell responses critical for control of acute Mabsc infection in healthy lungs remain relevant when Mabsc infection occurs in obstructed airways, rather than in the alveoli, as occurs in bronchiectasis. Using an agar bead model of Mabsc infection that prolongs murine small airway infection, replicates factors associated with bronchiectasis, and mirrors pathology of human Mabsc lung disease, we tested the hypothesis that Mabsc infection in obstructed airways elicits a qualitatively different immune response that alveolar Mabsc infection. We compared myeloid cell responses in in the two infection models using flow cytometric analyses of lung cells, immunofluorescent imaging, and histopathologic evaluation of lung sections. During the first 2 weeks of the bead model of Mabsc infection, absolute abundance of neutrophils in the lungs was significantly higher and relative abundance of recruited macrophages was lower than in the alveolar Mabsc infection model. Additionally, most resident alveolar macrophages (CD11c+ RAMs) in the bead model upregulated CD11b, a marker of inflammation, by 1-week post-infection and maintained high levels of CD11b expression at 3 weeks post infection despite infection occurring in airways, not alveoli. To understand the role of macrophage subsets in controlling Mabsc infection, clodronate liposomes were administered oropharyngeally to deplete RAMs. RAMs were essential for early control of alveolar Mabsc infection, but depletion of RAMs had no effect on control of Mabsc burden during bead infection. These studies demonstrate that murine Mabsc airway infection induced by obstructing small airways with Mabsc embedded in agar beads generates an immune milieu distinct from that induced by Mabsc infection in alveoli, altering the importance of different macrophage populations for control of infection.

PMID 42638801
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