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Chemical Compound Review

Bonefos     disodium [dichloro-(hydroxy-oxido...

Synonyms: Abioklad, Clasteon, Clastoban, Clodron, Clodronic Acid, ...
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Disease relevance of Dichloromethanediphosphonic acid


Psychiatry related information on Dichloromethanediphosphonic acid


High impact information on Dichloromethanediphosphonic acid


Chemical compound and disease context of Dichloromethanediphosphonic acid


Biological context of Dichloromethanediphosphonic acid


Anatomical context of Dichloromethanediphosphonic acid

  • METHODS: Between 1990 and 1995, 302 patients with primary breast cancer and tumor cells in the bone marrow (the presence of which is a risk factor for the development of distant metastases) were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for two years (157 patients) or standard follow-up (145 patients) [1].
  • RESULTS: After 1 year, the treatment effects for clodronate versus placebo in the lumbar spine, the total hip, and the trochanter, respectively, were as follows: +2.38% (95% confidence interval [CI] = 1.36-3.41), +0.74% (95% CI = -0.13 - 1.60), and +1.29% (95% CI = 0.24-2.34) [13].
  • 21 paraplegic patients with recent traumatic spinal cord injury were orally administered 400 (n = 7) or 1,600 (n = 7) mg/d of disodium dichloromethylene diphosphonate (Cl2MDP) and compared with a placebo group (n = 7) to test the preventive effects of the drug on acute bone loss and osteoclastic resorption [17].
  • Induction of proliferation and augmented cytotoxicity of gammadelta T lymphocytes by bisphosphonate clodronate [18].
  • Quantification of blood vessels in bone biopsy specimens from patients with Paget's disease before and after clodronate treatment showed a 40% reduction of the vascularization after BP treatment [19].

Associations of Dichloromethanediphosphonic acid with other chemical compounds


Gene context of Dichloromethanediphosphonic acid


Analytical, diagnostic and therapeutic context of Dichloromethanediphosphonic acid


  1. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. Diel, I.J., Solomayer, E.F., Costa, S.D., Gollan, C., Goerner, R., Wallwiener, D., Kaufmann, M., Bastert, G. N. Engl. J. Med. (1998) [Pubmed]
  2. Clodronate in metastatic breast cancer. Panasci, L.C., Sandor, V., Melnychuk, D. N. Engl. J. Med. (1998) [Pubmed]
  3. Use of dichloromethylene diphosphonate in metastatic bone disease. Jung, A., Chantraine, A., Donath, A., van Ouwenaller, C., Turnill, D., Mermillod, B., Kitler, M.E. N. Engl. J. Med. (1983) [Pubmed]
  4. Biodistribution of clodronate and liposomes used in the liposome mediated macrophage 'suicide' approach. Buiting, A.M., Zhou, F., Bakker, J.A., van Rooijen, N., Huang, L. J. Immunol. Methods (1996) [Pubmed]
  5. Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation. Stratis, A., Pasparakis, M., Rupec, R.A., Markur, D., Hartmann, K., Scharffetter-Kochanek, K., Peters, T., van Rooijen, N., Krieg, T., Haase, I. J. Clin. Invest. (2006) [Pubmed]
  6. Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization and tumor growth. Nakao, S., Kuwano, T., Tsutsumi-Miyahara, C., Ueda, S., Kimura, Y.N., Hamano, S., Sonoda, K.H., Saijo, Y., Nukiwa, T., Strieter, R.M., Ishibashi, T., Kuwano, M., Ono, M. J. Clin. Invest. (2005) [Pubmed]
  7. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. Cursiefen, C., Chen, L., Borges, L.P., Jackson, D., Cao, J., Radziejewski, C., D'Amore, P.A., Dana, M.R., Wiegand, S.J., Streilein, J.W. J. Clin. Invest. (2004) [Pubmed]
  8. Current use of bisphosphonates in oncology. International Bone and Cancer Study Group. Body, J.J., Bartl, R., Burckhardt, P., Delmas, P.D., Diel, I.J., Fleisch, H., Kanis, J.A., Kyle, R.A., Mundy, G.R., Paterson, A.H., Rubens, R.D. J. Clin. Oncol. (1998) [Pubmed]
  9. Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway. Virtanen, S.S., Väänänen, H.K., Härkönen, P.L., Lakkakorpi, P.T. Cancer Res. (2002) [Pubmed]
  10. Cyclical clodronate is effective in preventing postmenopausal bone loss: a comparative study with transcutaneous hormone replacement therapy. Filipponi, P., Pedetti, M., Fedeli, L., Cini, L., Palumbo, R., Boldrini, S., Massoni, C., Cristallini, S. J. Bone Miner. Res. (1995) [Pubmed]
  11. The effect of diphosphonates on heterotopic ossification in regenerating Achilles tendon of the mouse. McClure, J. J. Pathol. (1983) [Pubmed]
  12. Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury. Liu, T., van Rooijen, N., Tracey, D.J. Pain (2000) [Pubmed]
  13. Oral clodronate and reduction in loss of bone mineral density in women with operable primary breast cancer. Powles, T.J., McCloskey, E., Paterson, A.H., Ashley, S., Tidy, V.A., Nevantaus, A., Rosenqvist, K., Kanis, J. J. Natl. Cancer Inst. (1998) [Pubmed]
  14. Iron- and inflammation-induced hepcidin gene expression in mice is not mediated by Kupffer cells in vivo. Lou, D.Q., Lesbordes, J.C., Nicolas, G., Viatte, L., Bennoun, M., Van Rooijen, N., Kahn, A., Renia, L., Vaulont, S. Hepatology (2005) [Pubmed]
  15. Accelerated macrophage apoptosis induces autoantibody formation and organ damage in systemic lupus erythematosus. Denny, M.F., Chandaroy, P., Killen, P.D., Caricchio, R., Lewis, E.E., Richardson, B.C., Lee, K.D., Gavalchin, J., Kaplan, M.J. J. Immunol. (2006) [Pubmed]
  16. T cell-activated macrophages are capable of both recognition and rejection of pancreatic islet xenografts. Yi, S., Hawthorne, W.J., Lehnert, A.M., Ha, H., Wong, J.K., van Rooijen, N., Davey, K., Patel, A.T., Walters, S.N., Chandra, A., O'Connell, P.J. J. Immunol. (2003) [Pubmed]
  17. Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients. Minaire, P., Berard, E., Meunier, P.J., Edouard, C., Goedert, G., Pilonchery, G. J. Clin. Invest. (1981) [Pubmed]
  18. Induction of proliferation and augmented cytotoxicity of gammadelta T lymphocytes by bisphosphonate clodronate. Schilbach, K., Geiselhart, A., Handgretinger, R. Blood (2001) [Pubmed]
  19. Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Fournier, P., Boissier, S., Filleur, S., Guglielmi, J., Cabon, F., Colombel, M., Clézardin, P. Cancer Res. (2002) [Pubmed]
  20. A novel mechanism of complement-independent clearance of red cells deficient in glycosyl phosphatidylinositol-linked proteins. Jasinski, M., Pantazopoulos, P., Rother, R.P., van Rooijen, N., Song, W.C., Molina, H., Bessler, M. Blood (2004) [Pubmed]
  21. Evaluation of new bone resorption markers in a randomized comparison of pamidronate or clodronate for hypercalcemia of malignancy. Vinholes, J., Guo, C.Y., Purohit, O.P., Eastell, R., Coleman, R.E. J. Clin. Oncol. (1997) [Pubmed]
  22. Zoledronate sensitizes endothelial cells to tumor necrosis factor-induced programmed cell death: evidence for the suppression of sustained activation of focal adhesion kinase and protein kinase B/Akt. Bezzi, M., Hasmim, M., Bieler, G., Dormond, O., Rüegg, C. J. Biol. Chem. (2003) [Pubmed]
  23. The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis. Frith, J.C., Mönkkönen, J., Auriola, S., Mönkkönen, H., Rogers, M.J. Arthritis Rheum. (2001) [Pubmed]
  24. Distinctive roles of neutrophils and monocytes in anti-thy-1 nephritis. Westerhuis, R., van Straaten, S.C., van Dixhoorn, M.G., van Rooijen, N., Verhagen, N.A., Dijkstra, C.D., de Heer, E., Daha, M.R. Am. J. Pathol. (2000) [Pubmed]
  25. Synovial macrophage depletion with clodronate-containing liposomes in rheumatoid arthritis. Barrera, P., Blom, A., van Lent, P.L., van Bloois, L., Beijnen, J.H., van Rooijen, N., de Waal Malefijt, M.C., van de Putte, L.B., Storm, G., van den Berg, W.B. Arthritis Rheum. (2000) [Pubmed]
  26. Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines. Heikkilä, P., Teronen, O., Moilanen, M., Konttinen, Y.T., Hanemaaijer, R., Laitinen, M., Maisi, P., van der Pluijm, G., Bartlett, J.D., Salo, T., Sorsa, T. Anticancer Drugs (2002) [Pubmed]
  27. Monocyte chemoattractant protein-1 regulation of blood-brain barrier permeability. Stamatovic, S.M., Shakui, P., Keep, R.F., Moore, B.B., Kunkel, S.L., Van Rooijen, N., Andjelkovic, A.V. J. Cereb. Blood Flow Metab. (2005) [Pubmed]
  28. Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group. Lahtinen, R., Laakso, M., Palva, I., Virkkunen, P., Elomaa, I. Lancet (1992) [Pubmed]
  29. Intravenous clodronate in the treatment and retreatment of Paget's disease of bone. Yates, A.J., Percival, R.C., Gray, R.E., Atkins, R.M., Urwin, G.H., Hamdy, N.A., Preston, C.J., Beneton, M.N., Russell, R.G., Kanis, J.A. Lancet (1985) [Pubmed]
  30. Liposomal clodronate as a novel agent for treating autoimmune hemolytic anemia in a mouse model. Jordan, M.B., van Rooijen, N., Izui, S., Kappler, J., Marrack, P. Blood (2003) [Pubmed]
  31. Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer. Paterson, A.H., Powles, T.J., Kanis, J.A., McCloskey, E., Hanson, J., Ashley, S. J. Clin. Oncol. (1993) [Pubmed]
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