Disease relevance of Dichloromethanediphosphonic acid

• Reduction in new metastases in breast cancer with adjuvant clodronate treatment [1].
• Clodronate in metastatic breast cancer [2].
• There was a marginal decrease in bone resorption in the clodronate group and no change in bone accretion [3].
• Dichloromethylene diphosphonate (clodronate), a new compound, has powerful activity against osteoclasts and has been used successfully to treat hypercalcemia associated with cancer [3].
• Our results suggest that clodronate may be a useful adjuvant in managing metastatic bone disease [3].

Psychiatry related information on Dichloromethanediphosphonic acid

• Clodronate (Cl2MBP; dichloromethylene-bisphosphonate)-containing liposomes are used to investigate the role of macrophages in immune and non-immune defense mechanisms by elimination of these macrophages followed by functional studies [4].

High impact information on Dichloromethanediphosphonic acid

• The mean number of bony metastases per patient in the clodronate group was roughly half that in the control group (3.1 vs. 6.3) [1].
• In patients who have breast cancer and metastatic bone disease, the bisphosphonate clodronate (clodronic acid) reduces the frequency of skeletal complications [1].
• Elimination of skin macrophages by subcutaneous injection of clodronate liposomes was accompanied by inhibition of granulocyte migration into the skin and resulted in a dramatic attenuation of psoriasis-like skin changes [5].
• After day 4, clodronate liposomes, which kill macrophages, reduced IL-1beta-induced angiogenesis and partially inhibited VEGF-induced angiogenesis [6].
• Either systemic depletion of all bone marrow-derived cells (by irradiation) or local depletion of macrophages in the cornea (using clodronate liposomes) prior to injury significantly inhibited both hemangiogenesis and lymphangiogenesis [7].

Chemical compound and disease context of Dichloromethanediphosphonic acid

• They now constitute the standard treatment for cancer hypercalcemia, for which we recommend a dose of 1,500 mg of clodronate or 90 mg of pamidronate; the latter compound is more potent and has a longer lasting effect [8].
• They further suggest that interference with this pathway is involved in inhibition of invasion and migration of prostate cancer cells by the amino-BP alendronate but that the mechanism of clodronate inhibition is different [9].
• Both estrogen and clodronate prevent postmenopausal bone loss [10].
• The treatment of tenotomised animals with either disodium ethane-1, 1-diphosphonate (EHDP) or disodium dichloromethylene diphosphonate (Cl2MDP) has no effect on the process of heterotopic ossification which can be detected at the radiological or light microscopical level [11].
• Intravenous injection of liposome-encapsulated clodronate reduced the number of macrophages in the injured nerve, alleviated thermal hyperalgesia and protected both myelinated and unmyelinated fibres against degeneration [12].

Biological context of Dichloromethanediphosphonic acid

• Oral clodronate and reduction in loss of bone mineral density in women with operable primary breast cancer [13].
• Clodronate also inhibited invasion, but the IC50 was 0.1 microM [9].
• For this, we depleted Kupffer cells by injection of liposome-encapsulated clodronate and then studied iron- and inflammation-induced hepcidin gene expression [14].
• We have investigated whether increased Mphi apoptosis in vivo, induced by the administration of clodronate liposomes, can exacerbate the autoimmune phenotype in NZB x SWR (SNF(1)) lupus-prone mice, and induce autoantibody production in haplotype-matched BALB/c x DBA1 (DBF(1)) non-lupus-prone mice [15].
• Depletion of endogenous macrophages or any remaining CD4(+) T cells did not delay graft rejection in the macrophage-transferred FPP recipients, whereas depletion of transferred macrophages with clodronate liposomes prevented graft rejection [16].

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

• However, treatment with liposome-encapsulated clodronate, an agent that depletes macrophages in vivo, normalized the half-life of PIGA- RBCs [20].
• PATIENTS AND METHODS: Thirty-two patients with a serum calcium (sCa) level > or = 2.7 mmol/L that persisted after 48 hours of saline rehydration were randomized to receive pamidronate 90 mg or clodronate 1,500 mg [21].
• In this study we investigated the effects of zoledronate, a nitrogen-containing bisphosphonate, and clodronate, a non-nitrogen-containing bisphosphonate, on human umbilical vein endothelial cell (HUVEC) adhesion, migration, and survival, three events essential for angiogenesis [22].
• Unlike alendronate, clodronate and its metabolite did not affect prenylation of the small GTPase RaplA in osteoclasts or macrophages in vivo [23].
• In this study we investigated the distinctive roles of infiltrating PMNs or monocytes/macrophages by treating rats with an antibody against rat integrin CD11b/CD18 (ED7) or by depletion of monocytes with multilamellar clodronate liposomes, respectively [24].

Gene context of Dichloromethanediphosphonic acid

• Synovial macrophage depletion with clodronate-containing liposomes in rheumatoid arthritis [25].
• RESULTS: A single IA dose of clodronate liposomes significantly reduced the number of CD68-positive cells (P = 0.005) and the expression of ICAM-1 and VCAM-1 in the synovial lining (P = 0.013 and P = 0.039, respectively) [25].
• Bisphosphonates (clodronate, alendronate, pamidronate and zoledronate) at therapeutically attainable non-cytotoxic concentrations inhibited MMP-3, -12, -13 and -20 as well as MMP-1, -2, -8 and -9, but not urokinase-type plasminogen activator (uPA), a serine proteinase and a pro-MMP activator [26].
• Clodronate had no effect on HUVEC adhesion, migration, and survival nor did it enhanced TNF cytotoxicity [22].
• Monocytes/macrophages depletion (by clodronate liposomes) reduced the effect of MCP-1 on BBB permeability in vivo approximately 2 fold [27].

Analytical, diagnostic and therapeutic context of Dichloromethanediphosphonic acid

• Six patients in the clodronate group died, as did 22 in the control group (P=0.001) [1].
• Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group [28].
• Intravenous clodronate in the treatment and retreatment of Paget's disease of bone [29].
• Thus, in AIHA, liposomal clodronate therapy may act like a temporary, medicinal splenectomy [30].
• Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain) [31].

References