ETIDRONATE DISODIUM

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C2H6O7P2.2Na
Molecular Weight	249.9919
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=GWBBVOVXJZATQQ-UHFFFAOYSA-L

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

HIDE SMILES / InChI

Molecular Formula	Na
Molecular Weight	22.98976928
Charge	1
Count

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

Molecular Formula	C2H6O7P2
Molecular Weight	204.0124
Charge	-2
Count

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

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 2849
ATP 10 Target ID: CHEMBL2366048 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21111853	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Paget’s disease of bone 13 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017831s058lbl.pdf	Primary		Approved 8583	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 8583	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
Discovery of a high molecular weight complex of calcium, phosphate, fetuin, and matrix gamma-carboxyglutamic acid protein in the serum of etidronate-treated rats.	2002-02-08	11724771
Risedronate treatment and extended fracture protection in postmenopausal women.	2002-01-17	11791630
[Therapy of osteoporosis. Risk factors alone are not an indication].	2001-12-06	11813710
Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis.	2001-12	11728926
[Economic aspects of osteoporosis therapy. What does a prevented fracture cost?].	2001-11-22	11791359
Conventional treatment of hypercalcemia of malignancy.	2001-11-15	11757206
Advances in the biology and treatment of myeloma bone disease.	2001-11-15	11757204
A method to assess the proportion of treatment effect explained by a surrogate endpoint.	2001-11-15	11746311
[Alternatives to hormonal treatment for the prevention of postmenopausal osteoporosis: the bisphosphonates].	2001-11	11770280
Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage.	2001-11	11768198
Familial fibrodysplasia ossificans progressiva: trial with etidronate disodium.	2001-11	11721075
Role of alendronate and risedronate in preventing and treating osteoporosis.	2001-11	11718433
Extracellular signal-regulated kinases and calcium channels are involved in the proliferative effect of bisphosphonates on osteoblastic cells in vitro.	2001-11	11697801
Rhenium-188 HEDP to treat painful bone metastases.	2001-11	11595844
Clinical effect of etidronate on alveolar pyorrhoea associated with chronic marginal periodontitis: report of four cases.	2001-10-26	11675910
[Osteoporosis. Fracture as alarm signal].	2001-10-11	11721665
Treatment of osteoporosis in men with fluoride alone or in combination with bisphosphonates.	2001-10	11730262
Risedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy.	2001-10	11730260
Alendronate for the treatment of osteoporosis in men.	2001-10	11730259
Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy.	2001-10	11707007
Low-dose oral etidronate therapy for immobilization hypercalcaemia associated with Guillain-Barré syndrome.	2001-10	11697437
Maintenance of cancellous bone in ovariectomized, human parathyroid hormone [hPTH(1-84)]-treated rats by estrogen, risedronate, or reduced hPTH.	2001-10	11595618
Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity.	2001-10	11595616
Painful multifocal arthritis: therapy with rhenium 186 hydroxyethylidenediphosphonate ((186)Re HEDP) after failed treatment with medication--initial results of a prospective study.	2001-10	11568349
Zinc diphosphonates templated by organic amines: syntheses and characterizations of [NH3(CH2)2NH3]Zn(hedpH2)22H2O and [NH3(CH2)nNH3(CH2)nNH3]Zn2(hedpH)22H2O (n=4,5,6) (hedp=1-hydroxyethylidenediphophonate).	2001-09-10	11531453
[Risedronate now also approved for hip fractures. Study discloses significant risk reduction in proximal femoral neck fractures].	2001-09-06	11584532
[Optimizing treatment of osteoporosis. Rapidly effective therapy lowers fracture risk in 1 year up to 70%].	2001-09-06	11584531
Vgamma2Vdelta2 T-cell receptor-mediated recognition of aminobisphosphonates.	2001-09-01	11520816
Risedronate: a new oral bisphosphonate.	2001-09	11589256
Bisphosphonates for osteoporosis.	2001-09	11586803
The diagnosis of Paget's disease.	2001-09	11584586
Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures.	2001-09	11557372
Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning.	2001-09	11535725
Pharmacologic therapy for the treatment and prevention of osteoporosis.	2001-09	11532658
Guidelines for treatment of osteoporosis in men.	2001-08	11681154
186Re-1,4,8,11-tetraaza cyclotetradecyl-1,4,8,11-tetramethylene phosphonic acid: a novel agent for possible use in metastatic bone-pain palliation.	2001-08	11518653
Osteoporosis in children and adolescent girls: case report of idiopathic juvenile osteoporosis and review of the literature.	2001-08	11496161
Subcutaneous fat necrosis of the newborn following hypothermia and complicated by pain and hypercalcaemia.	2001-08	11488718
[Bisphosphonate treatment prevents hip fractures in 70-79 year old women with osteoporotic vertebral fractures].	2001-07-14	11484428
[Fluorides and bisphosphonates in the treatment of osteoporosis].	2001-07	11515184
[Tumor-induced hypercalcemia. Review of bisphosphonate treatment].	2001-07	11508158
A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer.	2001-07	11504074
Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis.	2001-07	11485341
Possibility of "distraction arthrogenesis": first report in rabbit model.	2001	11793183
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
Positive effect of etidronate therapy is maintained after drug is terminated in patients using corticosteroids.	2001	11748341
Etidronate for treating and preventing postmenopausal osteoporosis.	2001	11687195
Refractory heterotopic ossification with complications.	2001	11587419
Effect of intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis.	2001	11484098
Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane Collaboration methods for meta-analysis within economic evaluation.	2001	11465301

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 `Mon Mar 31 21:23:39 GMT 2025` Edited by `admin` on `Mon Mar 31 21:23:39 GMT 2025`
Record UNII	M16PXG993G
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ETIDRONATE DISODIUM

Official Name

English

DISODIUM ETIDRONATE

Preferred Name

English

ETIDRONATE DISODIUM [MART.]

Common Name

English

ETIDRONATE DISODIUM [VANDF]

Common Name

English

ETIDRONATE DISODIUM [EP MONOGRAPH]

Common Name

English

ETIDRONATE DISODIUM [ORANGE BOOK]

Common Name

English

TURPINAL 2NZ

Brand Name

English

NSC-759157

Code

English

ETIDRONATE DISODIUM [USP MONOGRAPH]

Common Name

English

Etidronate disodium [WHO-DD]

Common Name

English

ETIDRONATE DISODIUM [USP-RS]

Common Name

English

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

Common Name

English

ETIDRONIC ACID DISODIUM SALT [MI]

Common Name

English

DIDRONEL

Brand Name

English

ETIDRONATE DISODIUM [JAN]

Common Name

English

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

Common Name

English

ETIDRONIC ACID DISODIUM SALT

Common Name

English

Disodium dihydrogen (1-hydroxyethylidene)diphosphonate

Systematic Name

English

ETIDRONATE DISODIUM [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C443