Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C2H8O7P2.H2O |
| Molecular Weight | 224.0435 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O.CC(O)(P(O)(O)=O)P(O)(O)=O
InChI
InChIKey=KKNZXUHBWLPUFN-UHFFFAOYSA-N
InChI=1S/C2H8O7P2.H2O/c1-2(3,10(4,5)6)11(7,8)9;/h3H,1H3,(H2,4,5,6)(H2,7,8,9);1H2
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
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2363055 |
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Target ID: CHEMBL2366048 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | DIDRONEL Approved UseDidronel 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 Date1977 |
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| Preventing | DIDRONEL Approved UseDidronel 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 Date1977 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Possibility of "distraction arthrogenesis": first report in rabbit model. | 2001 |
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| 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 |
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| Etidronate for treating and preventing postmenopausal osteoporosis. | 2001 |
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| Effect of intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis. | 2001 |
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| Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane Collaboration methods for meta-analysis within economic evaluation. | 2001 |
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| Initiation of osteoporosis treatment after bone mineral density testing. | 2001 |
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| Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease. | 2001 |
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| Guidelines for treatment of osteoporosis in men. | 2001 Aug |
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| Subcutaneous fat necrosis of the newborn following hypothermia and complicated by pain and hypercalcaemia. | 2001 Aug |
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| Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis. | 2001 Dec |
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| [Therapy of osteoporosis. Risk factors alone are not an indication]. | 2001 Dec 6 |
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| A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. | 2001 Jul |
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| [Bisphosphonate treatment prevents hip fractures in 70-79 year old women with osteoporotic vertebral fractures]. | 2001 Jul 14 |
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| Clinical effect of etidronate on alveolar pyorrhoea associated with chronic marginal periodontitis: report of four cases. | 2001 Jul-Aug |
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| Prevalence and determinants of osteoporosis drug prescription among patients with high exposure to glucocorticoid drugs. | 2001 Jun |
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| Osteoporosis in men. | 2001 Jun 15 |
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| 186Re-etidronate. Efficacy of palliative radionuclide therapy for painful bone metastases. | 2001 Mar |
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| Radionuclide therapy for painful bone metastases. An Italian multicentre observational study. Writing Committee of an Ad Hoc Study Group. | 2001 Mar |
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| Response of cortical bone to antiresorptive treatment. | 2001 Mar |
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| Evidence-based medicine: putting theory into practice. | 2001 Mar |
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| Treatment of established bone loss after renal transplantation with etidronate. | 2001 Mar 15 |
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| Risedronate: clinical usage. | 2001 May |
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| Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption. | 2001 May |
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| Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. | 2001 May |
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| Absolute vs. relative numbers in evaluating drug therapy. | 2001 May 15 |
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| The effect of risedronate on the risk of hip fracture in elderly women. | 2001 May 31 |
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| [Alternatives to hormonal treatment for the prevention of postmenopausal osteoporosis: the bisphosphonates]. | 2001 Nov |
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| Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage. | 2001 Nov |
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| Familial fibrodysplasia ossificans progressiva: trial with etidronate disodium. | 2001 Nov |
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| Role of alendronate and risedronate in preventing and treating osteoporosis. | 2001 Nov |
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| Extracellular signal-regulated kinases and calcium channels are involved in the proliferative effect of bisphosphonates on osteoblastic cells in vitro. | 2001 Nov |
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| Conventional treatment of hypercalcemia of malignancy. | 2001 Nov 15 |
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| Advances in the biology and treatment of myeloma bone disease. | 2001 Nov 15 |
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| A method to assess the proportion of treatment effect explained by a surrogate endpoint. | 2001 Nov 15 |
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| [Economic aspects of osteoporosis therapy. What does a prevented fracture cost?]. | 2001 Nov 22 |
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| Risedronate treatment and extended fracture protection in postmenopausal women. | 2001 Nov-Dec |
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| Treatment of osteoporosis in men with fluoride alone or in combination with bisphosphonates. | 2001 Oct |
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| Risedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy. | 2001 Oct |
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| Alendronate for the treatment of osteoporosis in men. | 2001 Oct |
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| Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy. | 2001 Oct |
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| Low-dose oral etidronate therapy for immobilization hypercalcaemia associated with Guillain-Barré syndrome. | 2001 Oct |
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| 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 |
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| [Osteoporosis. Fracture as alarm signal]. | 2001 Oct 11 |
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| Risedronate: a new oral bisphosphonate. | 2001 Sep |
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| Bisphosphonates for osteoporosis. | 2001 Sep |
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| Pharmacologic therapy for the treatment and prevention of osteoporosis. | 2001 Sep |
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| Vgamma2Vdelta2 T-cell receptor-mediated recognition of aminobisphosphonates. | 2001 Sep 1 |
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| [Risedronate now also approved for hip fractures. Study discloses significant risk reduction in proximal femoral neck fractures]. | 2001 Sep 6 |
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| Positive effect of etidronate therapy is maintained after drug is terminated in patients using corticosteroids. | 2001 Winter |
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| 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 Feb 8 |
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.
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DTXSID8040800
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1268604
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25211-86-3
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4SQ327I33M
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12521030
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SUBSTANCE RECORD
