Usage
- Etidronate disodium is prescribed for the treatment of Paget’s disease of bone (osteitis deformans) and for the prevention and treatment of heterotopic ossification following total hip replacement or spinal cord injury. It is also occasionally used off-label for other conditions like myositis ossificans progressiva and calcinosis universalis.
- Pharmacological classification: Bisphosphonate, bone resorption inhibitor.
- Mechanism of Action: Etidronate inhibits bone resorption by adsorbing to hydroxyapatite crystals in bone, thereby interfering with the formation and dissolution of these crystals. This action reduces the number and activity of osteoclasts, slowing down the breakdown of bone.
Alternate Names
- International Nonproprietary Name (INN): Etidronate disodium
- Brand Names: Didronel
How It Works
- Pharmacodynamics: Etidronate primarily affects bone metabolism. It decreases bone resorption by inhibiting osteoclast activity. This leads to a reduction in serum alkaline phosphatase and urinary hydroxyproline levels, markers of bone turnover.
- Pharmacokinetics: Etidronate is poorly absorbed from the gastrointestinal tract. Absorption is further reduced by food, especially dairy products, and medications containing polyvalent cations (e.g., calcium, iron, magnesium, aluminum). About 50% of the absorbed drug is taken up by bone, while the remainder is excreted unchanged in the urine. It has an elimination half-life of 1 to 6 hours.
- Mode of Action: Etidronate adsorbs to hydroxyapatite crystals in the bone, inhibiting their formation and dissolution. This interferes with the process of bone resorption by osteoclasts. Etidronate does not directly bind to receptors, inhibit enzymes, or modulate neurotransmitters in the traditional sense.
- Elimination pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Paget’s Disease: Initial: 5 mg/kg/day orally once daily for up to 6 months. Alternatively, higher initial doses of 11-20 mg/kg/day may be used for up to 3 months in patients requiring more rapid response. The maximum dose is 20 mg/kg/day. Retreatment is initiated after a drug-free period of at least 90 days and only when there is evidence of disease reactivation.
- Heterotopic Ossification (Total Hip Replacement): 20 mg/kg/day orally once daily, starting 1 month before surgery and continuing for 3 months after surgery (4 months total).
- Heterotopic Ossification (Spinal Cord Injury): 20 mg/kg/day orally once daily for 2 weeks, followed by 10 mg/kg/day for 10 weeks (12 weeks total). Treatment should begin as soon as possible after injury.
Children:
Safety and efficacy have not been established in pediatric patients.
Special Cases:
- Elderly Patients: No specific dose adjustments are recommended, but caution is advised due to the potential for age-related decline in renal function.
- Patients with Renal Impairment: Dose reduction is recommended, but specific guidelines are not available. Close monitoring is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary, as etidronate is not metabolized in the liver.
- Patients with Comorbid Conditions: Use with caution in patients with gastrointestinal diseases, as etidronate can cause diarrhea. Monitor serum phosphate levels, especially in patients with renal insufficiency.
Clinical Use Cases
Etidronate is not indicated for use in clinical settings such as intubation, surgical procedures (other than total hip replacement), mechanical ventilation, intensive care unit (ICU) use, or emergency situations. Its use is limited to the specific indications mentioned above.
Dosage Adjustments
Dose adjustments may be necessary in patients with renal impairment or gastrointestinal disorders.
Side Effects
Common Side Effects:
- Diarrhea
- Nausea
- Bone pain
- Joint pain
Rare but Serious Side Effects:
- Osteonecrosis of the jaw
- Esophagitis
- Esophageal ulcers
- Atrial fibrillation (with IV administration)
- Osteomalacia (with prolonged high-dose therapy)
Long-Term Effects:
- Increased risk of fractures with prolonged high-dose therapy
- Osteomalacia with prolonged use
Adverse Drug Reactions (ADR):
- Hypersensitivity reactions (rare)
Contraindications
- Hypocalcemia
- Esophageal abnormalities that delay esophageal emptying (e.g., stricture, achalasia)
- Inability to stand or sit upright for at least 30 minutes
Drug Interactions
- Antacids, calcium supplements, and other medications containing polyvalent cations reduce etidronate absorption.
- Aspirin may increase the risk of gastrointestinal side effects.
- Food, especially dairy products, decreases etidronate absorption.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C
- Etidronate crosses the placenta and may pose risks to the developing fetus. Use only if the potential benefit outweighs the risk.
- It is not known if etidronate is excreted in breast milk. Use with caution during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits bone resorption by adsorbing to hydroxyapatite crystals.
- Side Effects: Diarrhea, nausea, bone pain, osteonecrosis of the jaw (rare).
- Contraindications: Hypocalcemia, esophageal abnormalities.
- Drug Interactions: Antacids, calcium supplements, food.
- Pregnancy & Breastfeeding: Category C, use with caution.
- Dosage: See dosage section above.
- Monitoring Parameters: Serum alkaline phosphatase, urinary hydroxyproline, serum calcium, and serum phosphate.
Popular Combinations
Etidronate is not typically used in combination with other drugs for its primary indications. Calcium and vitamin D supplementation is recommended to ensure adequate intake during etidronate therapy.
Precautions
- General Precautions: Monitor for signs of hypocalcemia, esophagitis, and osteonecrosis of the jaw. Ensure adequate calcium and vitamin D intake.
- Specific Populations: Use with caution in patients with renal impairment, gastrointestinal disorders, and during pregnancy and breastfeeding.
- Lifestyle Considerations: Patients should maintain good oral hygiene and avoid invasive dental procedures if possible during treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Etidronate?
A: See the detailed dosage guidelines provided above.
Q2: How should Etidronate be administered?
A: Administer orally on an empty stomach with a full glass of water, at least 2 hours before or after meals. If gastrointestinal discomfort occurs, the dose may be divided.
Q3: What are the most common side effects of Etidronate?
A: The most common side effects include diarrhea, nausea, and bone pain.
Q4: What are the serious side effects of Etidronate?
A: Serious side effects include osteonecrosis of the jaw, esophagitis, and esophageal ulcers.
Q5: Can Etidronate be used during pregnancy?
A: Etidronate is Pregnancy Category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Q6: Is Etidronate safe during breastfeeding?
A: It is not known if etidronate is excreted in breast milk. Use with caution during breastfeeding.
Q7: How does Etidronate interact with other medications?
A: Antacids, calcium supplements, and other medications containing polyvalent cations can decrease etidronate absorption. Separate administration by at least 2 hours.
Q8: What should patients avoid while taking Etidronate?
A: Patients should avoid food, especially dairy products, for at least 2 hours before and after taking etidronate. They should also avoid antacids and mineral supplements containing calcium, iron, magnesium, or aluminum within 2 hours of dosing.
Q9: What monitoring is required during Etidronate therapy?
A: Periodic monitoring of serum alkaline phosphatase, urinary hydroxyproline, serum calcium, and serum phosphate is recommended.
