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Etidronate Disodium

Class: Bone Resorption Inhibitors
VA Class: HS900
CAS Number: 7414-83-7
Brands: Didronel


Synthetic bisphosphonate; bone resorption inhibitor.c

Uses for Etidronate Disodium

Paget’s Disease of Bone

Used in the treatment of moderate to severe symptomatic Paget’s disease of bone (osteitis deformans).125 131 132 141 142 143 144 145 146

Efficacy not established in asymptomatic patients.125 May consider prophylactic treatment in patients with extensive involvement of the skull or spinal column and the possibility of irreversible neurologic damage or in those with extensive involvement threatening major joints or weight-bearing bones.125

Less effective than risedronate or alendronate in the treatment of moderate to severe Paget’s disease of bone.128 129 c 170

Relapse generally tends to occur within about 3–24 months in patients most likely to relapse (e.g., higher pretreatment markers of bone turnover).c

Resistance is most likely to develop in patients receiving >1 course of therapy per year or those with higher pretreatment indices of bone turnover.107

Heterotopic Ossification

Used in the prevention and treatment of heterotopic ossification (myositis ossificans, ectopic calcification, periarticular ossification, or paraosteoarthropathy) following total hip arthroplasty or resulting from spinal cord injury.125

Efficacy not established for treatment of idiopathic heterotopic ossification or heterotopic ossification associated with conditions other than total hip arthroplasty or spinal cord injury.c

Corticosteroid-induced Osteoporosis

Bisphosphonates, including etidronate, have been used effectively for the prevention and treatment of corticosteroid-induced osteoporosis.131 132 133 134 135 136 137 139 141 142 143 144 145 146 The American College of Rheumatology (ACR) currently recommends use of one of several other bisphosphonates (i.e., alendronate, risedronate, or zoledronic acid) in conjunction with lifestyle modification and calcium and vitamin D supplementation for the prevention and treatment of corticosteroid-induced osteoporosis in select postmenopausal women and men ≥50 years of age who are initiating or currently receiving corticosteroid therapy.166

Etidronate Disodium Dosage and Administration


Paget’s Disease of Bone

  • Monitor patients for recurrence of disease every 3–6 months.125 Consider retreatment only after a drug-free interval of ≥90 days following the previous course of therapy if biochemical, symptomatic, or other evidence of recurrence is present.125

Heterotopic Ossification

  • Initiate therapy as soon as it is feasible following spinal cord injury and preferably before any radiographic evidence of heterotopic ossification.125 Efficacy of retreatment has not been established in these patients nor in patients undergoing total hip arthroplasty.125


Oral Administration

Administer as a single daily dose with a full glass (180–240 mL) of water to facilitate absorption; may divide dosage if adverse GI effects occur.125 May be given with water125 c or fruit juice.c

Avoid lying down following oral administration.125

Avoid food, especially calcium-rich food (e.g., milk or milk products), vitamins with mineral supplements, or antacids that contain metals such as calcium, iron, magnesium, or aluminum for 2 hours before and after administration.125 c (See Food under Pharmacokinetics.)


Available as etidronate disodium; dosage expressed in terms of the salt.125


Paget’s Disease of Bone

Initially, 5–10 mg/kg daily for ≤6 months, or 11–20 mg/kg daily for ≤3 months, have been used.125 Recommended initial dosage is 5 mg/kg daily for ≤6 months.125

Onset of therapeutic response may be delayed,125 and therapeutic effects may persist for months following a course of therapy.125 (See Onset under Pharmacokinetics.) Avoid premature increases in dosage125 since increased dosage may cause mineralization defects.125 c

Patients who require immediate suppression of Paget’s disease or in whom lower dosages are ineffective: >10 mg/kg daily for ≤3 months.125 Use with caution.c

Dosages >20 mg/kg daily not recommended.125

Retreatment: Dosage usually the same as initial treatment.125 Consider increasing dosage within the recommended range if inadequate response with original dosage.125 (See General: Paget’s Disease of Bone under Dosage and Administration.)

Heterotopic Ossification
Prevention and Treatment

Spinal cord injury: Initially, 20 mg/kg daily for 2 weeks followed by 10 mg/kg daily for an additional 10 weeks (12 weeks total).125

Total hip arthroplasty: Initially, 20 mg/kg daily administered preoperatively for 1 month and postoperatively for an additional 3 months (4 months total).125

Corticosteroid-Induced Osteoporosis
Prevention and Treatment

400 mg daily for 2 weeks every 3 months has been used, usually in conjunction with calcium (e.g., 500 mg daily) and vitamin D supplementation during the remaining 10–11 weeks of each cycle or continuously.141 142 143 144 145 146 147

ACR recommends that bisphosphonate therapy be administered for as long as corticosteroid therapy continues.166

Prescribing Limits


Paget’s Disease of Bone

Maximum 20 mg/kg daily.125

Treatment duration: ≤6 months; continuous therapy for >6 months may increase the risk of fracture and osteomalacia.125

Special Populations

Renal Impairment

Reduce dosage in patients with reduced glomerular filtration; monitor such patients closely.125

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.125

Cautions for Etidronate Disodium


  • Esophageal abnormalities that delay esophageal emptying (e.g., stricture, achalasia).125

  • Known hypersensitivity to etidronate disodium.125



Upper GI Effects

Possible severe adverse esophageal effects (e.g., esophagitis, esophageal ulcers, erosions, strictures, perforation).125 (See Oral Administration under Dosage and Administration.) Monitor for any manifestations and discontinue if dysphagia, odynophagia, new or worsening heartburn, or retrosternal pain occurs.125

Risk of severe adverse esophageal effects greater in patients who do not drink 180–240 mL of water with etidronate, do not avoid lying down for ≥30 minutes following oral administration, and/or continue to take drug after developing symptoms suggesting esophageal irritation.125 Instruct patients carefully about proper administration and give copy of patient instructions provided by the manufacturer.125

Use with caution in patients with history of upper GI disease (e.g., Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis, ulcers).125 Gastric and duodenal ulcers (some severe and with complications) reported during postmarketing experience.125

General Precautions

Metabolic Effects

Maintain an adequate intake of calcium and vitamin D during therapy.125

Hyperphosphatemia may occur, especially with dosages of 10–20 mg/kg daily.125 (See Actions.) Usually returns to pretreatment values 2–4 weeks after treatment discontinuance.125


Therapy has been withheld in some patients with enterocolitis since diarrhea may occur, especially with high dosages.125

Musculoskeletal Effects

Impairs mineralization of new osteoid, principally in pagetic lesions and to a lesser extent in normal bone at dosages of 10–20 mg/kg daily.125 c Also may delay mineralization of ectopic bone.c Mineralization occurs normally following completion of therapy.125

Long bones affected mainly by lytic pagetic lesions, particularly in patients whose disease is unresponsive to therapy, may be especially prone to fractures.125 Monitor patients with predominantly lytic lesions closely, both radiographically and biochemically, to permit timely discontinuance of therapy in those whose disease is unresponsive.125 If fractures occur, may be advisable to delay or withhold therapy until callus is evident.125

Osteonecrosis and osteomyelitis of the jaw reported, principally in cancer patients receiving bisphosphonates, usually when given IV.125 147 148 149 150 151 Associated mostly with dental procedures (e.g., tooth extraction), but some cases occurred in patients with postmenopausal osteoporosis receiving oral therapy.125 Known risk factors include cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene, preexisting dental disease, anemia, coagulopathy, and infection.125

If osteonecrosis of the jaw develops, consult an oral surgeon for treatment.125 Dental surgery may exacerbate condition.125

In patients requiring dental procedures, no data are available to suggest whether discontinuance of therapy prior to procedure reduces the risk of osteonecrosis of the jaw.125 170 Base management of patients requiring dental treatment on an individual assessment of risks and benefits.125 170

Severe and occasionally incapacitating bone, joint, and/or muscle pain reported infrequently with bisphosphonate therapy.125 128 148 153 154 Time to onset varied from 1 day to years (mean onset about 3 months) after treatment initiation.125 128 148 153 154 Such pain generally improves following discontinuance, but may recur upon subsequent rechallenge with the same drug or another bisphosphonate.125 128 148 153 154

Atrial Fibrillation

Although data are conflicting, possible increased risk of atrial fibrillation with use of bisphosphonates.155 FDA analysis of data from long-term (6 months to 3 years) controlled trials identified a higher rate of atrial fibrillation in patients receiving bisphosphonates (alendronate, ibandronate, risedronate, or zoledronic acid) versus placebo; however, only a few events reported in each study.155 FDA is continuing to monitor this safety concern.155

Potential Risk of Esophageal Cancer

Some evidence (from postmarketing experience and observational studies) suggests a possible association between use of oral bisphosphonates and an increased risk of esophageal cancer.156 160 161 However, because of conflicting data,161 162 163 additional study needed to confirm such findings.160

FDA states that benefits of oral bisphosphonates continue to outweigh their potential risks in patients with osteoporosis; it is important to consider that esophageal cancer is rare, especially in women.160 161

Avoidance of oral bisphosphonates in patients with Barrett’s esophagus, a known precursor to esophageal adenocarcinoma, has been recommended.156

Specific Populations


Category C.125


Not known whether etidronate is distributed into milk.125 Use with caution.125

Pediatric Use

Safety and efficacy in children not established.125 Has been used in children for the prevention of heterotopic ossification or soft tissue calcification at weight-adjusted dosages recommended for adults.125

Rachitic syndrome reported infrequently in children receiving dosages of ≥10 mg/kg daily for approximately 1 year or longer.125 Epiphyseal radiographic changes associated with retarded mineralization of new osteoid and cartilage and associated occasional symptoms were reversible following discontinuance of the drug.125

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.125 (See Geriatric Patients under Dosage and Administration.)

Possible age-related impaired renal function and risk of toxic reactions; use with care.125 (See Renal Impairment under Cautions and under Dosage and Administration.)

Renal Impairment

Monitor patients with impaired renal function carefully.100 125 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Paget’s disease of bone: Bone pain, diarrhea, nausea.125

Heterotopic ossification: Diarrhea, nausea.125

Interactions for Etidronate Disodium

Specific Drugs





Increases in PT, mostly without clinically important sequelae125

Monitor PT when etidronate added to therapy125

Etidronate Disodium Pharmacokinetics



Approximately 3% of a dose is absorbed.125


Paget’s disease of bone: Reduced urinary excretion of hydroxyproline occurs after 1–3 months of therapy.c Reductions in markers of bone turnover reach a plateau in about 6 months.c


Paget’s disease of bone: May persist for ≥1 year following discontinuance of therapy.125 In patients whose disease is most likely to relapse, relapse generally tends to occur within about 3–24 months.c

Heterotropic ossification: Persists for ≥9 months following drug discontinuance.125


Food decreases extent of absorption.c



Following oral administration, about 50% of absorbed drug distributed almost exclusively into bone.125 c Eliminated slowly (weeks to years) via bone turnover.100 101 106 125

Drug does not cross blood-brain barrier in animals.125

Not known whether etidronate is distributed into milk.125



No evidence of metabolism.125

Elimination Route

Excreted unchanged in urine (approximately half of an absorbed dose)101 within 24 hours.125 Unabsorbed drug is excreted intact in feces.125


Plasma elimination half-life is 1–6 hours.125 Terminal half-life estimated to be 394 days.173





25°C (may be exposed to 15–30°C).125


  • Adsorbs to hydroxyapatite crystals and their amorphous precursors in bone matrix and inhibits their aggregation, growth, mineralization, and dissolution.125 c

  • Heterotopic ossification: Prevents or slows the formation of heterotopic bone during the active stage.125 c

  • Paget’s disease of bone: Reduces the number of osteoclasts and osteoblasts.125

  • Paget’s disease of bone: Reduces rate of bone turnover as evidenced by decreases in markers of bone turnover and reduced radionuclide uptake at pagetic lesions.125 c

  • Paget’s disease of bone: Reduces vascularity of pagetic bone, skin temperature over superficially located pagetic lesions, and cardiac output.125 c

  • Can increase serum phosphate concentration by increasing renal tubular reabsorption of phosphate.125 c

  • No immunosuppressive activity in animal studies.104

Advice to Patients

  • Importance of proper administration (e.g., avoiding food, vitamins with mineral supplements, or antacids that contain metals for 2 hours before and after administration).125

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.125

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.125

  • Importance of informing patients of other important precautionary information.125 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Etidronate Disodium


Dosage Forms


Brand Names




200 mg



400 mg

Didronel (scored)


AHFS DI Essentials. © Copyright 2018, Selected Revisions March 21, 2012. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


Only references cited for selected revisions after 1984 are available electronically.

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