Etidronic acid (Etidronate) (10 mM, 24 h) exhibits cytotoxicity, causing p53 alterations in MCF-7 cells as well as a decrease in the S phase population and an increase in the G2/M population [3]. Osteoclast apoptosis is induced by etipidric acid (100 nM, 24 h), and fluorescence microscopy reveals the features of this process, such as chromatin condensation and modifications to nuclear and cellular morphology [5].

Absorption, Distribution and Excretion
The oral bioavailability of etidronic acid is 1-10%. Pharmacokinetic data for etidronic acid are not yet available. Absorbed etidronic acid is excreted in the urine, and unabsorbed drug is excreted in the feces. The volume of distribution of etidronic acid is 0.3-1.3 L/kg. The renal clearance of etidronic acid is 0.09 L/kg/h. The distribution of technetium-99M HEDP in normal human organs has been determined. The bone-binding agent (99M)TC-SN-1-hydroxyethylmethylene-1,1-bisphosphonic acid unexpectedly binds to human articular cartilage and cortical bone particles in vitro. In addition to the simple ionic attraction between the HEDP phosphonate group and metal cations (e.g., Ca2+), other mechanisms lead to the absorption of (99M)TC-HEDP by body tissues.
Characteristics of (99)TC-hydroxyethyl bisphosphonate (TC-HEDP) binding to human serum albumin showed an affinity constant of 7.8 × 10⁺⁴. A single slope was obtained.

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Metabolism/Metabolites
Etidronate is not metabolized in vivo.
Non-metabolized.
Elimination pathway: Etidronate disodium is not metabolized. Approximately half of the absorbed dose is excreted in the urine within 24 hours; the remainder is distributed to the bones and is slowly eliminated. Unabsorbed drug is excreted intact in the feces.
Half-life: Based on a non-compartmental pharmacokinetic model, the half-life of etidronate in the plasma of normal subjects is 1 to 6 hours.

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Biological half-life
The half-life of etidronate sodium is approximately 1–6 hours.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Since there is currently no information on the use of etidronate sodium during lactation, alternative medications are recommended, especially for breastfed newborns or premature infants. However, breastfed infants are unlikely to absorb etidronate sodium. ◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

[1]. Dunn CJ, et al. Etidronic acid. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs Aging. 1994 Dec;5(6):446-74.
[2]. Ariyoshi T, et al. Effect of etidronic acid on arterial calcification in dialysis patients. Clin Drug Investig. 2006;26(4):215-22.
[3]. Zhou Y, et al. Cytotoxicity of etidronic acid to human breast cancer cells. Ethn Dis. 2008 Spring;18(2 Suppl 2):S2-87-92.
[4]. Zhu S, et al. In-Depth Study of Heavy Metal Removal by an Etidronic Acid-Functionalized Layered Double Hydroxide. ACS Appl Mater Interfaces. 2022 Feb 9;14(5):7450-7463.
[5]. Kameda T, et al. Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts. J Exp Med. 1997 Aug 18;186(4):489-95.

Etidromic acid is a 1,1-bisphosphonic acid, specifically ethane-1,1-diylbisphosphonic acid, with a hydroxyl substituent at the 1-position. It acts on the surface of calcium phosphate through chemisorption, inhibiting the formation, growth, and dissolution of hydroxyapatite crystals. It has dual functions of maintaining bone density, chelation, and antitumor activity. It is the conjugate acid of etidronic acid (2-). Etidromic acid is a first-generation bisphosphonate, similar to clodronic acid and teludronic acid. These drugs were developed to mimic the effects of pyrophosphate, a substance that regulates calcification and decalcification. In recent years, the use of etidronic acid has gradually decreased, replaced by third-generation nitrogen-containing bisphosphonates such as zoledronic acid, ibandronic acid, minodronic acid, and risedronic acid. Etidromic acid was approved by the U.S. Food and Drug Administration (FDA) on September 1, 1977. Etidromic acid is a bisphosphonate. Etidronate belongs to the bisphosphonate class of drugs, and its difference from endogenous pyrophosphates lies in its resistance to enzymatic hydrolysis. This drug adsorbs onto hydroxyapatite cells, reducing the number of osteoclasts and thus inhibiting abnormal bone resorption. Etidronate may also directly stimulate osteoblasts to form bone tissue. (NCI) Etidronate is only present in individuals who have used or taken this drug. It is a bisphosphonate that affects calcium metabolism. It inhibits ectopic calcification and slows bone resorption and bone turnover. [PubChem] After binding to bone tissue, bisphosphonates are absorbed by osteoclasts (bone cells that break down bone tissue). Although the mechanism of action of non-nitrogen bisphosphonates is not fully elucidated, existing data suggest that they bind tightly to hydroxyapatite crystals in the bone matrix, especially in areas of active bone turnover, and inhibit crystal formation and dissolution. Other effects may include directly inhibiting the function of mature osteoclasts, promoting osteoclast apoptosis, and interfering with osteoblast-mediated osteoclast activation. Etidronate does not interfere with bone mineralization. In malignant tumor-associated hypercalcemia, etidronate lowers serum calcium levels by inhibiting tumor-induced bone resorption and reducing calcium inflow from resorbed bone tissue into the bloodstream. Etidronate also reduces the incidence of osteolytic bone metastases by inhibiting tumor-induced bone resorption. Etidronate may promote osteoclast apoptosis by competing with adenosine triphosphate (ATP) in cellular energy metabolism. Osteoclasts initiate apoptosis and die, leading to a reduction in overall bone breakdown.
A bisphosphonate that affects calcium metabolism. It inhibits ectopic calcification and slows bone resorption and bone turnover.
See also: Etidronate monohydrate (note moved to).
Pharmaceutical Indications

Etidronate sodium is indicated for the treatment of Paget's disease and for the treatment and prevention of ectopic ossification after total hip arthroplasty following spinal cord injury.
FDA Label
Mechanism of Action

Bisphosphonates bind to hydroxyapatite after being absorbed by bone. Bone resorption by osteoclasts leads to local acidification, releasing bisphosphonates, which are then absorbed by osteoclasts via liquid-phase endocytosis. After acidification of the endocytic vesicles, bisphosphonates are released into the osteoclast cytosol to exert their effects. Osteoclasts mediate bone resorption. When osteoclasts bind to bone, they form foot processes, which are ring structures of F-actin. Disruption of the foot processes causes osteoclasts to detach from the bone, thus preventing bone resorption. First-generation bisphosphonates have a structure very similar to pyrophosphate, which can be incorporated into non-hydrolyzable ATP analogs, thereby disrupting all ATP-mediated effects of osteoclasts. Male rats were injected with the excipient (control group), 0.4 or 4.0 mg/kg/day of ethane-1-hydroxy-1,1-bisphosphonate (EHDP). After 6 days of EHDP treatment, all rats received 6 subcutaneous injections of (3)H-thymidine at 8-hour intervals. Pretreatment with EHDP for 6 days followed by administration of EHDP at a dose of 4.0 mg/kg/day reduced the multiple labeling index of osteoprogenitor cells. EHDP increased the incorporation and accumulation rate of (3)H-thymidine nuclei in osteoclasts. Although EHDP slowed bone resorption, it still accelerated the differentiation of osteoclasts from progenitor cells into osteoclasts.

C2H8O7P2

206.02832

205.974

2809-21-4

Etidronic acid disodium;7414-83-7

3305

White to off-white solid powder

2.1±0.1 g/cm3

578.8±60.0 °C at 760 mmHg

198~199℃

303.8±32.9 °C

0.0±3.6 mmHg at 25°C

1.586

-3.54

5

7

2

11

211

0

OC(P(O)(O)=O)(P(O)(O)=O)C

DBVJJBKOTRCVKF-UHFFFAOYSA-N

InChI=1S/C2H8O7P2/c1-2(3,10(4,5)6)11(7,8)9/h3H,1H3,(H2,4,5,6)(H2,7,8,9)

(1-hydroxy-1-phosphonoethyl)phosphonic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~485.37 mM)
H2O : ~100 mg/mL (~485.37 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (12.13 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (12.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (485.37 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)