Etidronic acid

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Etidronic acid
Etidronic acid.svg
Clinical data
Trade names Didronel, others
Other names1-Hydroxyethylidene-1,1-diphosphonic acid; HEDP
AHFS/Drugs.com International Drug Names
License data
Routes of
administration
Oral, intravenous
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 3%
Metabolism Nil
Elimination half-life 1 to 6 hours
Excretion Renal and fecal
Identifiers
  • (1-Hydroxyethan-1,1-diyl)bis(phosphonic acid)
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.018.684 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C2H8O7P2
Molar mass 206.027 g·mol−1
3D model (JSmol)
  • O=P(O)(O)C(O)(C)P(=O)(O)O
  • InChI=1S/C2H8O7P2/c1-2(3,10(4,5)6)11(7,8)9/h3H,1H3,(H2,4,5,6)(H2,7,8,9) Yes check.svgY
  • Key:DBVJJBKOTRCVKF-UHFFFAOYSA-N Yes check.svgY
   (verify)

Etidronic acid, also known as etidronate, is a bisphosphonate drug. [1] It is non-nitrogenous bisphosphonate. It was patented in 1966 and approved for medical use in 1977. [2] For medicinal purposes, etidronic acid has been obsolete since the early 2010's. [3]

Contents

Use

Medical

Etidronic acid is a bisphosphonate once used to strengthen bone, treat osteoporosis, and treat Paget's disease of bone.

Bisphosphonates primarily reduce osteoclastic activity, which prevents bone resorption, and thus moves the bone resorption/formation equilibrium toward the formation side and hence makes bone denser in the long run. Etidronate, unlike other bisphosphonates, also prevents bone calcification. For this reason, other bisphosphonates, such as alendronate, are preferred when fighting osteoporosis. To prevent bone resorption without affecting too much bone calcification, etidronate is administered only for a short time once in a while, for example for two weeks every 3 months. When given on a continuous basis, say every day, etidronate will altogether prevent bone calcification. This effect may be useful and etidronate was in fact used this way to fight heterotopic ossification. But in the long run, if used on a continuous basis, it will cause osteomalacia.

Chemical

HEDP is a versatile phosphonate compound known for its corrosion inhibition, chelating, and stabilizing properties, making it valuable across a range of industrial and consumer applications.

In industrial contexts, HEDP acts as a retardant of cement hydration in concrete, extending the dormant period before hardening begins. [4] It is also used as a scale and corrosion inhibitor in circulating cooling water systems, oil fields, and low-pressure boilers, serving industries such as electric power, chemical manufacturing, metallurgy, and fertilizer production.

Beyond these applications, HEDP is utilized in the dyeing industry as a peroxide stabilizer and dye-fixing agent, and in non-cyanide electroplating where it functions as a chelating agent. In the light woven industry, it serves as a detergent for cleaning metal and non-metal surfaces and is often combined with polycarboxylic acids (superplasticizers) as a reducing agent. Typical dosages range from 1–10 mg/L for scale inhibition, 10–50 mg/L for corrosion inhibition, and 1000–2000 mg/L for detergent use.

As a chelating agent, HEDP binds to calcium, iron, and other metal ions, helping to reduce their potential environmental impact, particularly through greywater discharge into groundwater. Its phosphonate structure also imparts corrosion resistance to unalloyed steel, and it retards rancidification and oxidation of fatty acids.

In detergents and cleaning agents, HEDP and its salts help mitigate the adverse effects of hard water and stabilize peroxides during bleaching by inhibiting degradation caused by transition metals. Within the cosmetics industry, HEDP is used as a radical formation suppressant, emulsion stabilizer, and viscosity control agent. Although approved for use in cosmetic products, it is recommended that products containing HEDP, particularly soaps, be thoroughly rinsed from the skin after use.

HEDP also finds application in swimming pool maintenance, where it functions as a stain inhibitor by preventing metal ions from precipitating and staining pool surfaces.

Pharmacology

Relative potency [5]
BisphosphonateRelative potency
Etidronate1
Tiludronate 10
Pamidronate 100
Alendronate 100-500
Ibandronate 500-1000
Risedronate 1000
Zoledronate 5000

Synthesis

Etidronic acid can be prepared by reactions of dialkylphosphites and carboxylic acid anhydrides. [6] Other precursors include phosphorus trichloride and phosphorous acid. [7]

References

  1. Russell RG (2011). "Bisphosphonates: The first 40 years". Bone. 49 (1): 2–19. doi:10.1016/j.bone.2011.04.022. PMID   21555003.
  2. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 523. ISBN   978-3-527-60749-5.
  3. Ebetino FH, Hogan AM, Sun S, Tsoumpra MK, Duan X, Triffitt JT, et al. (2011). "The relationship between the chemistry and biological activity of the bisphosphonates". Bone. 49 (1): 20–33. doi:10.1016/j.bone.2011.03.774. PMID   21497677.
  4. Axthammer D, Dengler J (2024). "Cement retarding mechanism of phosphonates and their interaction with aluminium". Materials Advances. 5 (14): 5974–5983. doi:10.1039/D4MA00299G.
  5. Tripathi KD (2013-09-30). Essentials of medical pharmacology (Seventh ed.). New Delhi: Jaypee Brothers Medical Publishers Pvt. Limited. ISBN   978-93-5025-937-5. OCLC   868299888.
  6. Cade JA (1959). "449. Methylenebisphosphonates and related compounds. Part II. Synthesis from α-keto-phosphonates". Journal of the Chemical Society (Resumed): 2272–2275. doi:10.1039/jr9590002272.
  7. "Etidronic Acid". PubChem. U.S. National Library of Medicine. Use and manufacturing. CID 3305. Retrieved 3 February 2015.