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

Medically reviewed by on Mar 2, 2022. Written by ASHP.


Synthetic bisphosphonate; bone resorption inhibitor.

Uses for Etidronate

Paget Disease of Bone

Used in the treatment of moderate to severe symptomatic Paget disease of bone (osteitis deformans).

Efficacy not established in asymptomatic patients. 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.

Less effective than risedronate or alendronate in the treatment of moderate to severe Paget disease of bone.

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

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

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.

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

Glucocorticoid-induced Osteoporosis

Bisphosphonates, including etidronate, have been used effectively for the prevention and treatment of glucocorticoid-induced osteoporosis.

Etidronate Dosage and Administration


Paget Disease of Bone

  • Monitor patients for recurrence of disease every 3–6 months. 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.

Heterotopic Ossification

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


Oral Administration

Administer as a single daily dose with a full glass (180–240 mL) of plain water to facilitate absorption; may divide dosage if adverse GI effects occur.

Avoid lying down following oral administration.

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. (See Food under Pharmacokinetics.)


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


Paget Disease of Bone

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

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

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

Dosages >20 mg/kg daily not recommended.

Retreatment: Dosage usually the same as initial treatment. Consider increasing dosage within the recommended range if inadequate response with original dosage. (See General: Paget 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).

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

Glucocorticoid-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.

Prescribing Limits


Paget Disease of Bone

Maximum 20 mg/kg daily.

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

Special Populations

Renal Impairment

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

Geriatric Patients

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

Cautions for Etidronate


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

  • Known hypersensitivity to etidronate disodium.



Upper GI Effects

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

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. Instruct patients carefully about proper administration and give copy of patient instructions provided by the manufacturer.

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

General Precautions

Metabolic Effects

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

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


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

Osteonecrosis of the Jaw

Osteonecrosis and osteomyelitis of the jaw reported, principally in cancer patients receiving bisphosphonates, usually when given IV. Mostly associated with tooth extraction and/or local infection with delayed healing, but some cases occurred in patients with postmenopausal osteoporosis receiving oral therapy. Known risk factors include cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, preexisting dental disease, anemia, coagulopathy, and infection.

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

In patients requiring dental procedures, discontinuance of therapy prior to procedure may reduce the risk of osteonecrosis of the jaw. Base management of patients requiring dental treatment on an individual assessment of risks and benefits.

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. Also may delay mineralization of ectopic bone. Mineralization occurs normally following completion of therapy.

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

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

Atrial Fibrillation

Although data are conflicting, possible increased risk of atrial fibrillation with use of bisphosphonates. 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. FDA is continuing to monitor this safety concern.

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. However, because of conflicting data, additional study needed to confirm such findings.

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.

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

Specific Populations


Category C.


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

Pediatric Use

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

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

Geriatric Use

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

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

Renal Impairment

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

Common Adverse Effects

Paget disease of bone: Bone pain, diarrhea, nausea.

Heterotopic ossification: Diarrhea, nausea.

Interactions for Etidronate

Specific Drugs





Increases in PT, mostly without clinically important sequelae

Monitor PT when etidronate added to therapy

Etidronate Pharmacokinetics



Approximately 3% of a dose is absorbed.


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


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

Heterotopic ossification: Persists for ≥9 months following drug discontinuance.


Food decreases extent of absorption.



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

Drug does not cross blood-brain barrier in animals.

Not known whether etidronate is distributed into milk.



No evidence of metabolism.

Elimination Route

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


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





25°C (may be exposed to 15–30°C).


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

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

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

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

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

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

  • No immunosuppressive activity in animal studies.

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).

  • 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.

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

  • Importance of informing patients of other important precautionary information. (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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Etidronate Disodium


Dosage Forms


Brand Names




200 mg*

Etidronate Disodium Tablets

400 mg*

Etidronate Disodium Tablets

AHFS DI Essentials™. © Copyright 2022, Selected Revisions March 12, 2018. 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.

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