ETIDRONATE TETRASODIUM

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C2H4O7P2.4Na
Molecular Weight	293.9556
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[Na+].[Na+].[Na+].CC(O)(P([O-])([O-])=O)P([O-])([O-])=O

InChI

InChIKey=KWXLCDNSEHTOCB-UHFFFAOYSA-J

InChI=1S/C2H8O7P2.4Na/c1-2(3,10(4,5)6)11(7,8)9;;;;/h3H,1H3,(H2,4,5,6)(H2,7,8,9);;;;/q;4*+1/p-4

HIDE SMILES / InChI

Molecular Formula	C2H4O7P2
Molecular Weight	201.9965
Charge	-4
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017831s058lbl.pdf |

Etidronate is a salt of etidronic acid (brand name Didronel, also known as EHDP) a diphosphonate, which is indicated for the treatment of symptomatic Paget’s disease of bone and in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury. Didronel is not approved for the treatment of osteoporosis. This drugs acts primarily on bone. It can inhibit the formation, growth, and dissolution of hydroxyapatite crystals and their amorphous precursors by chemisorption to calcium phosphate surfaces. Inhibition of crystal resorption occurs at lower doses than are required to inhibit crystal growth. Both effects increase as the dose increases. Preclinical studies indicate etidronate disodium does not cross the blood-brain barrier. Didronel is not metabolized. The amount of drug absorbed after an oral dose is approximately 3 percent. Bisphosphonates, when attached to bone tissue, are absorbed by osteoclasts, the bone cells that breaks down bone tissue. Although the mechanism of action of non-nitrogenous bisphosphonates has not been fully elucidated, available data suggest that they bind strongly to hydroxyapatite crystals in the bone matrix, preferentially at the sites of increased bone turnover and inhibit the formation and dissolution of the crystals. Other actions may include direct inhibition of mature osteoclast function, promotion of osteoclast apoptosis, and interference with osteoblast-mediated osteoclast activation. Etidronic acid may promote osteoclast apoptosis by competing with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hydroxyapatite 20 Target ID: CHEMBL2363055 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16046206	Antagonist 2778
ATP 10 Target ID: CHEMBL2366048 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21111853	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Paget’s disease of bone 12 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017831s058lbl.pdf	Primary		Approved 8429	DIDRONEL Approved Use Didronel is indicated for the treatment of symptomatic Paget’s disease of bone and in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury. Didronel is not approved for the treatment of osteoporosis. Paget’s Disease: Didronel is indicated for the treatment of symptomatic Paget's disease of bone. Didronel therapy usually arrests or significantly impedes the disease process as evidenced by: --Symptomatic relief, including decreased pain and/or increased mobility (experienced by 3 out of 5 patients). --Reductions in serum alkaline phosphatase and urinary hydroxyproline levels (30 percent or more in 4 out of 5 patients). --Histomorphometry showing reduced numbers of osteoclasts and osteoblasts, and more lamellar bone formation. Bone scans showing reduced radionuclide uptake at pagetic lesions. In addition, reductions in pagetically elevated cardiac output and skin temperature have been observed in some patients. In many patients, the disease process will be suppressed for a period of at least 1 year following cessation of therapy. The upper limit of this period has not been determined. The effects of the Didronel treatment in patients with asymptomatic Paget's disease have not been studied. However, Didronel treatment of such patients may be warranted if extensive involvement threatens irreversible neurologic damage, major joints, or major weight-bearing bones. Heterotopic Ossification: Didronel is indicated in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury. Didronel reduces the incidence of clinically important heterotopic bone by about two-thirds. Among those patients who form heterotopic bone, Didronel retards the progression of immature lesions and reduces the severity by at least half. Follow-up data (at least 9 months posttherapy) suggest these benefits persist. In total hip replacement patients, Didronel does not promote loosening of the prosthesis or impede trochanteric reattachment. In spinal cord injury patients, Didronel does not inhibit fracture healing or stabilization of the spine. Launch Date 1977
Heterotopic ossification 7 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017831s058lbl.pdf	Preventing		Approved 8429	DIDRONEL Approved Use Didronel is indicated for the treatment of symptomatic Paget’s disease of bone and in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury. Didronel is not approved for the treatment of osteoporosis. Paget’s Disease: Didronel is indicated for the treatment of symptomatic Paget's disease of bone. Didronel therapy usually arrests or significantly impedes the disease process as evidenced by: --Symptomatic relief, including decreased pain and/or increased mobility (experienced by 3 out of 5 patients). --Reductions in serum alkaline phosphatase and urinary hydroxyproline levels (30 percent or more in 4 out of 5 patients). --Histomorphometry showing reduced numbers of osteoclasts and osteoblasts, and more lamellar bone formation. Bone scans showing reduced radionuclide uptake at pagetic lesions. In addition, reductions in pagetically elevated cardiac output and skin temperature have been observed in some patients. In many patients, the disease process will be suppressed for a period of at least 1 year following cessation of therapy. The upper limit of this period has not been determined. The effects of the Didronel treatment in patients with asymptomatic Paget's disease have not been studied. However, Didronel treatment of such patients may be warranted if extensive involvement threatens irreversible neurologic damage, major joints, or major weight-bearing bones. Heterotopic Ossification: Didronel is indicated in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury. Didronel reduces the incidence of clinically important heterotopic bone by about two-thirds. Among those patients who form heterotopic bone, Didronel retards the progression of immature lesions and reduces the severity by at least half. Follow-up data (at least 9 months posttherapy) suggest these benefits persist. In total hip replacement patients, Didronel does not promote loosening of the prosthesis or impede trochanteric reattachment. In spinal cord injury patients, Didronel does not inhibit fracture healing or stabilization of the spine. Launch Date 1977

PubMed

Title	Date	PubMed
Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate.	2001	11793169
Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane Collaboration methods for meta-analysis within economic evaluation.	2001	11465301
Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis.	2001 Dec	11728926
Skeletal uptake and soft-tissue retention of 186Re-HEDP and 153Sm-EDTMP in patients with metastatic bone disease.	2001 Feb	11216521
Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group.	2001 Feb 1	11172164
[Bisphosphonate treatment prevents hip fractures in 70-79 year old women with osteoporotic vertebral fractures].	2001 Jul 14	11484428
Osteoporosis in men.	2001 Jun 15	11430449
186Re-etidronate. Efficacy of palliative radionuclide therapy for painful bone metastases.	2001 Mar	11456380
Hip fractures: do preventive drugs work for all?	2001 Mar	11263091
Prevention of secondary osteoporosis postmenopause in hemiplegia.	2001 Mar	11237270
Prevention and treatment of osteoporosis.	2001 Mar-Apr	11333463
Risedronate increases bone mineral density and reduces the vertebral fracture incidence in postmenopausal women.	2001 Mar-Apr	11326471
Incadronate and etidronate accelerate phosphate-primed mineralization of MC4 cells via ERK1/2-Cbfa1 signaling pathway in a Ras-independent manner: further involvement of mevalonate-pathway blockade for incadronate.	2001 May	11430477
Risedronate: clinical usage.	2001 May	11406915
Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption.	2001 May	11348880
Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro.	2001 May	11344045
Absolute vs. relative numbers in evaluating drug therapy.	2001 May 15	11388707
[Alternatives to hormonal treatment for the prevention of postmenopausal osteoporosis: the bisphosphonates].	2001 Nov	11770280
Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage.	2001 Nov	11768198
Familial fibrodysplasia ossificans progressiva: trial with etidronate disodium.	2001 Nov	11721075
Role of alendronate and risedronate in preventing and treating osteoporosis.	2001 Nov	11718433
Conventional treatment of hypercalcemia of malignancy.	2001 Nov 15	11757206
Advances in the biology and treatment of myeloma bone disease.	2001 Nov 15	11757204
Risedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy.	2001 Oct	11730260
Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy.	2001 Oct	11707007
Low-dose oral etidronate therapy for immobilization hypercalcaemia associated with Guillain-Barré syndrome.	2001 Oct	11697437
Maintenance of cancellous bone in ovariectomized, human parathyroid hormone [hPTH(1-84)]-treated rats by estrogen, risedronate, or reduced hPTH.	2001 Oct	11595618
Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity.	2001 Oct	11595616
[Osteoporosis. Fracture as alarm signal].	2001 Oct 11	11721665
Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning.	2001 Sep	11535725
Vgamma2Vdelta2 T-cell receptor-mediated recognition of aminobisphosphonates.	2001 Sep 1	11520816
Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase.	2001 Sep 7	11435429
Positive effect of etidronate therapy is maintained after drug is terminated in patients using corticosteroids.	2001 Winter	11748341

Patents

Sample Use Guides

In Vivo Use Guide

should be taken as a single, oral dose. Paget’s Disease: Initial Treatment Regimens: 5 to 10 mg/kg/day, not to exceed 6 months, or 11 to 20 mg/kg/day, not to exceed 3 months. The recommended initial dose is 5 mg/kg/day for a period not to exceed 6 months. Doses above 10 mg/kg/day should be reserved for when 1) lower doses are ineffective or 2) there is an overriding need to suppress rapid bone turnover (especially when irreversible neurologic damage is possible) or reduce elevated cardiac output. Doses in excess of 20 mg/kg/day are not recommended.

Route of Administration: Oral

In Vitro Use Guide

In vitro cytotoxicity of etidronic acid to MCF-7 cells was estimated on the basis of clonogenicity assays, while cell cycle effects were determined by using flow cytometry. A 24-hour treatment with etidronic acid (10 mM) with or without strontium chloride was cytototoxic to MCF-7cells. Etidronic acid (1, 10 mM) caused a decrease in the S-phase population and an increase in the G2/M population. Treatment of MCF-7 human breast cancer cells with etidronic acid (10 mM) for six hours caused mutations in exons 6 and 8 of the p53 gene in MCF-7 cells.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 04:54:50 GMT 2023` Edited by `admin` on `Sat Dec 16 04:54:50 GMT 2023`
Record UNII	CZZ9T1T1X4
Record Status	`Validated (UNII)`
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Name

Type

Language

ETIDRONATE TETRASODIUM

Common Name

English

TETRASODIUM ETIDRONATE [INCI]

Common Name

English

TETRASODIUM ETIDRONATE

Official Name

English

Etidronate tetrasodium [WHO-DD]

Common Name

English

PHOSPHONIC ACID, (1-HYDROXYETHYLIDENE)BIS-, TETRASODIUM SALT

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C443