U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C2H7O7P2.Na
Molecular Weight 228.0101
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MONOSODIUM ETIDRONATE

SMILES

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

InChI

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

HIDE SMILES / InChI

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

Molecular Formula C2H7O7P2
Molecular Weight 205.0203
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2366048
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

2.4192E11
Preventing
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

2.4192E11
PubMed

PubMed

TitleDatePubMed
[TNF-alpha secretion by human macrophage-like cells in response to wear particles and its modification by drugs].
1999 May
Possibility of "distraction arthrogenesis": first report in rabbit model.
2001
Etidronate for treating and preventing postmenopausal osteoporosis.
2001
Initiation of osteoporosis treatment after bone mineral density testing.
2001
A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis.
2001
Subcutaneous fat necrosis of the newborn following hypothermia and complicated by pain and hypercalcaemia.
2001 Aug
[Therapy of osteoporosis. Risk factors alone are not an indication].
2001 Dec 6
Treatment of osteoporosis with bisphosphonates.
2001 Feb
Skeletal uptake and soft-tissue retention of 186Re-HEDP and 153Sm-EDTMP in patients with metastatic bone disease.
2001 Feb
Ulcerative esophagitis caused by etidronate.
2001 Feb
Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group.
2001 Feb 1
Effect of high doses of oral risedronate (20 mg/day) on serum parathyroid hormone levels and urinary collagen cross-link excretion in postmenopausal women with spinal osteoporosis.
2001 Jan
Oesophageal transit, disintegration and gastric emptying of a film-coated risedronate placebo tablet in gastro-oesophageal reflux disease and normal control subjects.
2001 Jan
Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis.
2001 Jul
Prevalence and determinants of osteoporosis drug prescription among patients with high exposure to glucocorticoid drugs.
2001 Jun
Evidence-based medicine: putting theory into practice.
2001 Mar
Prevention and treatment of osteoporosis.
2001 Mar-Apr
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
Absolute vs. relative numbers in evaluating drug therapy.
2001 May 15
[Bisphosphonates in osteoporosis. Significantly reduces risk of fracture].
2001 May 3
The effect of risedronate on the risk of hip fracture in elderly women.
2001 May 31
Role of alendronate and risedronate in preventing and treating osteoporosis.
2001 Nov
Extracellular signal-regulated kinases and calcium channels are involved in the proliferative effect of bisphosphonates on osteoblastic cells in vitro.
2001 Nov
Rhenium-188 HEDP to treat painful bone metastases.
2001 Nov
Advances in the biology and treatment of myeloma bone disease.
2001 Nov 15
Alendronate for the treatment of osteoporosis in men.
2001 Oct
Bisphosphonates for osteoporosis.
2001 Sep
Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures.
2001 Sep
Patents

Patents

Sample Use Guides

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 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 08:29:37 UTC 2023
Edited
by admin
on Sat Dec 16 08:29:37 UTC 2023
Record UNII
BCZ8ETH6PD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MONOSODIUM ETIDRONATE
Common Name English
PHOSPHONIC ACID, P,P'-(1-HYDROXYETHYLIDENE)BIS-, SODIUM SALT (1:1)
Systematic Name English
MONOSODIUM (1-HYDROXYETHYLIDENE)-1,1-DIPHOSPHONATE
Common Name English
Code System Code Type Description
EPA CompTox
DTXSID601031599
Created by admin on Sat Dec 16 08:29:37 UTC 2023 , Edited by admin on Sat Dec 16 08:29:37 UTC 2023
PRIMARY
PUBCHEM
23687324
Created by admin on Sat Dec 16 08:29:37 UTC 2023 , Edited by admin on Sat Dec 16 08:29:37 UTC 2023
PRIMARY
CAS
29329-71-3
Created by admin on Sat Dec 16 08:29:37 UTC 2023 , Edited by admin on Sat Dec 16 08:29:37 UTC 2023
NON-SPECIFIC STOICHIOMETRY
CAS
13529-88-9
Created by admin on Sat Dec 16 08:29:37 UTC 2023 , Edited by admin on Sat Dec 16 08:29:37 UTC 2023
PRIMARY
FDA UNII
BCZ8ETH6PD
Created by admin on Sat Dec 16 08:29:37 UTC 2023 , Edited by admin on Sat Dec 16 08:29:37 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY