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| Other Sizes |
| Targets |
Clodronate targets osteoclasts and bone mineral (hydroxyapatite). As a bisphosphonate, it binds with high affinity to calcium ions on the surface of hydroxyapatite crystals in bone. Once bound, it is internalized by osteoclasts during bone resorption. Clodronate is a non-nitrogenous bisphosphonate that is metabolized to a toxic ATP analog, which induces osteoclast apoptosis. This reduces osteoclast-mediated bone resorption and bone turnover. The compound also inhibits hydroxyapatite crystal formation and dissolution. These mechanisms underlie its anti-osteoporotic effects.
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| ln Vitro |
Clodronate disodium tetrahydrate is a first-generation bisphosphonate that acts by blocking VNUT, a crucial molecule that starts purinergic chemical events, to greatly reduce neuropathic and neuropathic pain unrelated to disruptive disorders [1]. connection as a medication that resists bone absorption [2].
Clodronate exhibits in vitro activity by inhibiting osteoclast differentiation and function. In osteoclast cultures, clodronate reduces the number of osteoclasts and inhibits bone resorption activity. The compound binds to hydroxyapatite and is taken up by osteoclasts, leading to apoptosis. In vitro assays using osteoclasts or bone marrow cultures are used to assess its activity. Clodronate’s effects on bone resorption are measured by the release of calcium or other bone resorption markers. These in vitro activities confirm its potential as an anti-osteoporotic agent. |
| ln Vivo |
By blocking VNUT, clodronate tetrahydrate (10 mg/kg; IV) reduces accommodative discomfort [1]. Disodium clodronate tetrahydrate inhibits VNUT, which reduces accommodative pain [1].
Clodronate is used in vivo as an anti-osteoporotic drug. In animal models of osteoporosis (e.g., ovariectomized rats), clodronate reduces bone loss and improves bone mineral density. It is administered orally or parenterally. The compound binds to bone and remains there for extended periods, providing sustained inhibition of bone resorption. In humans, clodronate is used for the prevention and treatment of osteoporosis in post-menopausal women and men. It is also used to treat Paget’s disease and bone metastases. |
| Enzyme Assay |
In vitro assays for clodronate involve measuring its binding to hydroxyapatite and its effects on osteoclast activity. Hydroxyapatite binding assays use radiolabeled clodronate to measure its affinity for bone mineral. Osteoclast activity assays use osteoclasts cultured on bone or dentine slices; the area of resorption pits is measured. Osteoclast apoptosis is assessed by TUNEL staining or caspase activity assays. These assays confirm the compound’s mechanism of action and its effects on bone resorption.
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| Cell Assay |
In vitro cellular assays for clodronate are conducted in osteoclast cultures, which can be derived from bone marrow or from the RAW 264.7 macrophage cell line stimulated with RANKL. Cells are treated with clodronate at various concentrations, and osteoclast differentiation is assessed by TRAP staining. Bone resorption is measured by quantifying calcium release or by analyzing resorption pit formation on bone slices. Osteoclast apoptosis is assessed by flow cytometry or caspase activity assays. These assays characterize the compound’s anti-osteoclastic activity.
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| Animal Protocol |
Animal/Disease Models: C57BL/6 mice (22-30 g) [1]
Doses: 10 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results: Reduce inflammatory pain caused by carrageenan or complete Freund's adjuvant (CFA) . In vivo animal experiments with clodronate are conducted in rodent models of osteoporosis, such as ovariectomized rats. Clodronate is administered orally or by injection at varying doses. Bone mineral density is measured by DEXA or micro-CT. Bone turnover markers are measured in serum and urine. Histomorphometric analysis of bone sections is performed to assess osteoclast number and bone formation. These studies confirm the compound’s efficacy in preventing bone loss. |
| ADME/Pharmacokinetics |
Clodronate has limited oral bioavailability (<5%) due to its high polarity and poor absorption. It is rapidly cleared from the circulation and binds extensively to bone mineral. The compound is not metabolized and is excreted unchanged in the urine. Its half-life in plasma is short, but its residence time in bone is long, providing sustained therapeutic effects. The compound is typically administered on an intermittent schedule for osteoporosis treatment.
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| Toxicity/Toxicokinetics |
Clodronate is generally well-tolerated, but common adverse effects include gastrointestinal disturbances (nausea, diarrhea) and transient hypocalcemia. Renal toxicity can occur with rapid intravenous administration. Osteonecrosis of the jaw is a rare but serious adverse effect associated with bisphosphonate therapy. The compound is contraindicated in patients with severe renal impairment or hypocalcemia. Its safety profile is well-established from clinical use.
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| References | |
| Additional Infomation |
Disodium clodronate tetrahydrate is the tetrahydrate of Disodium clodronate salt. It inhibits bone resorption and soft tissue calcification and can be used as an adjunct therapy for severe hypercalcemia associated with malignant tumors, as well as osteolytic lesions and bone pain associated with bone metastases. It helps maintain bone density. It is a hydrate and a single-carbon compound. It contains Disodium clodronate salt. Disodium clodronate salt is the disodium salt of a nitrogen-free bisphosphonate analog of natural pyrophosphate. Clodronate binds to calcium, inhibiting osteoclast-mediated bone resorption and the formation and dissolution of hydroxyapatite crystals, thereby reducing bone turnover. This drug can control hypercalcemia associated with malignant tumors, inhibit osteolytic bone metastases, and relieve pain. A bisphosphonate that affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.
Clodronate disodium tetrahydrate is a first-generation bisphosphonate used as an anti-osteoporotic drug. It is also known as clodronic acid disodium salt tetrahydrate. The compound binds to bone and inhibits osteoclastic bone resorption, reducing bone turnover. It is used for the prevention and treatment of osteoporosis in post-menopausal women and men. It is also used to treat Paget’s disease of bone and bone metastases. The compound is available in various formulations for research and clinical use. |
| Molecular Formula |
CH2CL2NA2O6P2
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|---|---|
| Molecular Weight |
288.8560
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| Exact Mass |
359.892
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| CAS # |
88416-50-6
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| Related CAS # |
Clodronic acid disodium salt;22560-50-5;Clodronic acid;10596-23-3
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| PubChem CID |
23724874
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| Appearance |
White to off-white solid powder
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| LogP |
1.049
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
206
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XWHPUCFOTRBMGS-UHFFFAOYSA-L
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| InChi Code |
InChI=1S/CH4Cl2O6P2.2Na.4H2O/c2-1(3,10(4,5)6)11(7,8)9;;;;;;/h(H2,4,5,6)(H2,7,8,9);;;4*1H2/q;2*+1;;;;/p-2
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| Chemical Name |
disodium;[dichloro-[hydroxy(oxido)phosphoryl]methyl]-hydroxyphosphinate;tetrahydrate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~125 mg/mL (~346.34 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 25 mg/mL (69.27 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4619 mL | 17.3094 mL | 34.6188 mL | |
| 5 mM | 0.6924 mL | 3.4619 mL | 6.9238 mL | |
| 10 mM | 0.3462 mL | 1.7309 mL | 3.4619 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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