| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
Etidronate disodium targets bone mineral (hydroxyapatite) and osteoclast function. It binds strongly to calcium phosphate crystals on the bone surface, forming a barrier that prevents osteoclast attachment and resorption. Additionally, etidronate is internalized by osteoclasts and inhibits farnesyl pyrophosphate synthase, an enzyme in the mevalonate pathway, leading to apoptosis of osteoclasts. This dual mechanism reduces bone turnover and increases bone mass.
|
|---|---|
| ln Vitro |
Etidronate (10 mM, 24 h) disodium exhibits cytotoxicity, causing p53 alterations in MCF-7 cells and a decrease in the S phase population and an increase in the G2/M population [3]. Osteoclast apoptosis is induced by disodium etidronic acid (100 nM, 24 h), and alterations in cell and nuclear morphology as well as chromatin condensation are visible through fluorescence microscopy analysis [5].
In vitro, etidronate disodium inhibits the formation of calcium phosphate precipitates and prevents the dissolution of hydroxyapatite crystals. It reduces osteoclast-mediated bone resorption in bone organ cultures. Etidronate also inhibits the activity of farnesyl pyrophosphate synthase in cell-free assays with an IC50 in the micromolar range. In osteoclast cultures, etidronate induces apoptosis and reduces the number of resorption pits. |
| ln Vivo |
In vivo, etidronate disodium effectively reduces bone turnover and increases bone mineral density in postmenopausal women with osteoporosis. In Paget's disease, it reduces elevated serum alkaline phosphatase and urinary hydroxyproline levels, indicating decreased bone resorption. It also prevents heterotopic ossification in patients following hip surgery. In animal models, etidronate prevents bone loss in ovariectomized rats and reduces osteolytic lesions in tumor-bearing mice.
|
| Enzyme Assay |
In vitro enzyme/receptor binding assays for etidronate are not typical because it targets bone mineral. However, its inhibition of farnesyl pyrophosphate synthase can be assessed by enzyme activity assays using recombinant enzyme and radiolabeled substrates. The IC50 for inhibition is determined. Binding to hydroxyapatite can be measured by adsorption studies using radiolabeled etidronate. Osteoclast resorption assays involve culturing osteoclasts on bone slices and measuring resorption pit area.
|
| Cell Assay |
In vitro cellular assays for etidronate disodium are performed using osteoclast precursors (e.g., RAW 264.7 cells differentiated with RANKL) or isolated osteoclasts. Cells are treated with etidronate, and cell viability is assessed by MTT. Apoptosis is evaluated by caspase activity. Osteoclast differentiation and activity are assessed by TRAP staining and resorption pit assays. The compound's effect on osteoblast proliferation can also be studied using osteoblast cell lines.
|
| Animal Protocol |
In vivo animal experiments for etidronate disodium are conducted in ovariectomized rats, a model of postmenopausal osteoporosis. Rats are treated with etidronate orally or subcutaneously, and bone mineral density is measured by DXA. Bone turnover markers (e.g., serum osteocalcin, urine deoxypyridinoline) are analyzed. Histomorphometry of bone sections is performed to assess osteoclast number and bone formation. Efficacy in Paget's disease is evaluated in models with enhanced bone turnover.
|
| ADME/Pharmacokinetics |
Etidronate disodium has a molecular weight of 249.99 g/mol (anhydrous) and a molecular formula of C2H6Na2O7P2. It is a white crystalline powder, soluble in water. Oral bioavailability is low (about 3-5%) due to poor absorption, and it is rapidly cleared from plasma. The compound binds to bone and is retained for long periods; its half-life in bone is years. Etidronate is not metabolized and is excreted unchanged in urine. It should be taken on an empty stomach to improve absorption.
|
| Toxicity/Toxicokinetics |
Etidronate disodium is generally well-tolerated, but common side effects include nausea, diarrhea, and abdominal pain, especially at high doses. It can cause hyperphosphatemia and, rarely, osteomalacia with prolonged use due to inhibition of mineralization. Renal toxicity has been reported with rapid intravenous administration. Contraindications include severe renal impairment and hypersensitivity. Long-term use requires monitoring of bone turnover and renal function.
|
| References |
|
| Additional Infomation |
Etidronate sodium is an organozinc salt formed by replacing two protons (one for each phosphonic acid group) of etidronic acid with sodium ions. It has effects such as maintaining bone density, antitumor activity, and chelation. It contains an etidronic acid (2-) group. Etidronate sodium is a synthetic therapeutic bisphosphonate and an analogue of endogenous pyrophosphate. As a member of the bisphosphonate class, etidronate sodium differs from endogenous pyrophosphate in its resistance to enzymatic hydrolysis. This drug adsorbs onto hydroxyapatite cells, reducing the number of osteoclasts and thus inhibiting abnormal bone resorption. Etidronate sodium may also directly stimulate osteoblasts to form bone. (NCI04) A bisphosphonate that affects calcium metabolism. It inhibits ectopic calcification and slows bone resorption and bone turnover. See also: etidronic acid (with active moiety).
Etidronate disodium is a first-generation bisphosphonate approved for the treatment of osteoporosis, Paget's disease, and hypercalcemia. It is also used to prevent heterotopic ossification. Although less potent than newer bisphosphonates (e.g., alendronate), it was the first bisphosphonate to be widely used. Its ability to inhibit both bone resorption and mineralization has led to the development of more selective agents. Etidronate is still used in some countries and is available as a generic drug. |
| Molecular Formula |
C2H6NA2O7P2
|
|---|---|
| Molecular Weight |
249.9919
|
| Exact Mass |
249.938
|
| CAS # |
7414-83-7
|
| Related CAS # |
Etidronic acid;2809-21-4;Etidronic acid-d3 disodium;358730-93-5
|
| PubChem CID |
23894
|
| Appearance |
White to off-white solid powder
|
| Boiling Point |
578.8ºC at 760 mmHg
|
| Melting Point |
> 300ºC
|
| Flash Point |
303.8ºC
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
13
|
| Complexity |
206
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
GWBBVOVXJZATQQ-UHFFFAOYSA-L
|
| InChi Code |
InChI=1S/C2H8O7P2.2Na/c1-2(3,10(4,5)6)11(7,8)9;;/h3H,1H3,(H2,4,5,6)(H2,7,8,9);;/q;2*+1/p-2
|
| Chemical Name |
disodium;hydroxy-[1-hydroxy-1-[hydroxy(oxido)phosphoryl]ethyl]phosphinate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
H2O : ~50 mg/mL (~200.01 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0002 mL | 20.0008 mL | 40.0016 mL | |
| 5 mM | 0.8000 mL | 4.0002 mL | 8.0003 mL | |
| 10 mM | 0.4000 mL | 2.0001 mL | 4.0002 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
