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Description: A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification. [PubChem]
Drug Type: Small Molecule; Approved; Investigational
Pharmacology: Clodronate is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and tiludronate. Clodronate affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the clodronate that is resorbed (from oral preparation) or infused (for intravenous drugs), about 50% is excreted unchanged by the kidney. The remainder has a very high affinity for bone tissue, and is rapidly absorbed onto the bone surface. Clodronate has been shown to prevent or delay skeletal-related events and decrease bone pain as well as normalize calcium levels in the presence of hypercalcemia.
Mechanism of Action: The bisphosphonate group binds strongly to the bone mineral, hydroxyapatite. This explains the specific pharmacological action of these compounds on mineralized tissues, especially bone. The exact mechanism of action of clodronate is not known, however it is known that it does not inhibit protein isoprenylation but can be metabolized intracellularly to a β-γ-methylene (AppCp-type) analog of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. Inhibition of the ADP/ATP translocase by the metabolite AppCCl2p is a likely route by which clodronate causes osteoclast apoptosis and inhibits bone resorption. Recently, the slime mold Dictyostelium discoideum was shown to take up bisphosphonates by pinocytosis. In these cells, clodronate, but not other pharmacologically active bisphosphonates, was incorporated into adenine nucleotides, which could potentially explain why this bisphosphonate sometimes seems to act differently than the other bisphosphonates. Clodronate, like all biphosphonates, also binds protein-tyrosine-phosphatase.
Indication: For the management of hypercalcemia of malignancy and as an adjunct in the management of osteolysis resulting from bone metastases of malignant tumors.
Half Life: Approximately 13 hours.
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Data Correlations | 3 studies

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Genes category icon Genes
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PTPN1 100 100
SLC25A6 100 100
SLC25A5 100 100
SLC25A4 100 100
Lcn4 100 100
5430413K10Rik 97 97
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Biogroups category icon Biogroups
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Globoside Metabolism 100 100
Mitochondrial substrate carrier 99 99
Complement C1q protein 99 99
Glycosphingolipid Biosynthesis Glob… 98 98
Collagen helix repeat 98 98
Calcium Signaling Pathway 98 98
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Individual Studies

  • Olfactory epithelium of liposome-encapsulated clodronate (Lip-C) treated mice

    Mus musculus Mus musculus | RNA Expression   RNA Expression

    Comparison of gene expression in olfactory epithelium of sham and 48 hr olfactory bulbectomy (OBX) Lip-O (empty vessicle) mice versus Lip-C mice.

    Authors: Borders S Aaron, Hersh A Matthew, Getchell L Marilyn et al.

    Organization: University of Kentucky Anatomy and Neuro…

  • Drug target sets for approved compounds

    Homo sapiens Homo sapiens | Therapeutic   Therapeutic

    The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information.

    Authors: David S Wishart, Craig Knox, An Chi Guo et al.

    Organization: Department of Computing Science, Univers…
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Associated Researchers

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Thought leaders and organizations working on research involving clodronate.

View All Author iconAuthors
  • Nico van Rooijen
  • David P Dearnaley
  • L Vehmanen
  • Francesca PierigĂ©
  • Mark Stott
View All Clinical trial sponsors icon Clinical Trials Sponsors
  • Southwest Oncology Group
  • NCIC Clinical Trials Group
  • German Breast Group
  • Bayer
  • Kuopio University Hospital
View All Affiliations icon Organizations
  • University of Urbino
  • Helsinki University Central Hospital
  • Cardiff University
  • George Washington University Medical Center
  • Institute of Cancer Research and Royal Marsden Hospital

Clinical Trials | 14 trials

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