Etidronate is a bisphosphonate medication primarily used in the treatment of osteoporosis and Paget's disease of bone. Bisphosphonates like etidronate work by inhibiting the breakdown of bone, thereby increasing bone density and strength.

Osteoporosis is a condition characterized by weakened bones, making them more susceptible to fractures. Paget's disease of bone is a condition where there is excessive and abnormal bone remodeling, leading to weak, misshapen bones.

Etidronate (Etibon) is a bisphosphonate that takes calcium from the blood to the bones. It is used to treat patients with Paget's disease, osteoporosis, and other conditions resulting in hypercalcemia such as multiple myeloma.

Etidronate (Etibon) Uses:

• Paget disease:
  • It is the symptomatic treatment of Paget disease of bone
• Heterotopic ossification:
  • It is the prevention and treatment of heterotopic ossification due to spinal cord injury or after total hip replacement.

Etidronate (Etibon) Dose in Adults

If dietary intake is inadequate patients should receive supplemental calcium and vitamin D.

Etidronate (Etibon) Dose in the treatment of Paget disease: Oral:

• Starting dose:
  • It's usually between 5 to 10 milligrams per kilogram of body weight per day, but not for more than 6 months.
  • Or, it can be between 11 to 20 milligrams per kilogram of body weight per day, but not for more than 3 months.
  • The suggested starting dose is 5 milligrams per kilogram of body weight per day, but again, not for more than 6 months.
• Higher doses:
  • If the lower doses aren't working or if there's a need to slow down bone turnover quickly to prevent possible nerve damage or reduce elevated heart output, then higher doses can be used.
  • But doses above 10 milligrams per kilogram per day should only be used if lower doses didn't work.
  • Doses over 20 milligrams per kilogram per day aren't recommended.
• Re-treatment:
  • If a person needs more treatment after stopping etidronate, they should wait at least 90 days before starting again.
  • Doctors should check on patients every 3 to 6 months.
  • The re-treatment doses are the same as the starting doses.
  • If the original dose didn't work well enough, doctors might consider increasing it within the recommended limits.

Etidronate (Etibon) Dose in the treatment of Heterotopic ossification: Oral:

• Caused by spinal cord injury:
  • Start with 20 milligrams per kilogram of body weight per day for 2 weeks.
  • Then, reduce the dose to 10 milligrams per kilogram of body weight per day for 10 weeks.
  • The total treatment time is 12 weeks.
• Complicating total hip replacement:
  • Take 20 milligrams per kilogram of body weight per day for 1 month before the hip replacement surgery.
  • After surgery, continue with the same dose (20 mg/kg/day) for 3 months.
  • The total treatment time is 4 months.

For re-treatment:

• There isn't enough study data available for re-treatment. This means there are no established guidelines for using etidronate again after completing a course of treatment for heterotopic ossification.

Etidronate (Etibon) Dose in Children

Etidronate (Etibon) Dose in the treatment of Heterotopic ossification, traumatic brain injury: 

When treating heterotopic ossification caused by traumatic brain injury in children and adolescents with etidronate taken by mouth, here's how the dosage typically works based on the limited available data:

• Initial dose: Start with 20 milligrams per kilogram of body weight per dose, once daily, for 2 to 4 weeks.
• Maintenance dose: After the initial period, decrease the dose to 10 milligrams per kilogram of body weight per dose, once daily, for 12 weeks to 1 year.

Pregnancy Risk Factor: C

• Bisphosphonates, like other medications, have a rating for their risk during pregnancy, which is category C.
• While studies in animals have shown some adverse effects, it's not clear if bisphosphonates can pass through the placenta to the fetus, but it's expected that they can.
• Bisphosphonates are stored in the bone and gradually released over time.
• While there's theoretical concern about potential harm to the fetus if a woman becomes pregnant after completing bisphosphonate therapy, available data haven't shown a significant increase in fetal risks.
• However, it's generally recommended to stop bisphosphonate treatment in women planning to become pregnant, especially since hypocalcemia (low calcium levels) has been reported in babies exposed to bisphosphonates in the womb.
• Close monitoring of babies born to mothers who took bisphosphonates during pregnancy is advised.

Etidronate use during breastfeeding:

• It's uncertain whether etidronate passes into breast milk.
• The manufacturer advises caution when giving etidronate to breastfeeding women.
• This means that while there isn't enough information to confirm whether etidronate is present in breast milk, it's still suggested to be careful when considering its use in nursing mothers.

Dose in Kidney Disease:

• The manufacturer's instructions advise reducing the dose of etidronate when the glomerular filtration rate (GFR), which measures kidney function, is decreased.
• However, they don't specify the exact dosage adjustments to make.
• It's crucial to use etidronate cautiously and to closely monitor individuals with reduced kidney function because etidronate is eliminated from the body through the kidneys without undergoing any changes.

Dose in Liver disease:

In the manufacturer's labeling, no dosage adjustments are provided.

Side effects of Etidronate (Etibon):

• Gastrointestinal:
  • Nausea
  • Diarrhea
• Neuromuscular & skeletal:
  • Ostealgia

Contraindications to Etidronate (Etibon):

• Etidronate should not be used in individuals who have a known hypersensitivity to bisphosphonates or any ingredient in the formulation.
• It's also contraindicated in cases of overt osteomalacia, a condition where bones become weak and soft.
• Additionally, etidronate is not recommended for patients with esophageal abnormalities such as strictures or achalasia, which can slow down the emptying of the esophagus.
• These conditions can increase the risk of complications when taking etidronate, so it's important to avoid its use in such cases.

Warnings and precautions

Bone/ joint/ muscle pain:

• While taking bisphosphonates like etidronate, some individuals may experience bone, joint, or muscle pain, although this occurs infrequently.
• In some cases, this pain can be severe and even debilitating.
• The onset of this pain can vary, occurring from just one day to several months after starting treatment.
• If patients experience severe symptoms, it's advisable to consider discontinuing therapy.
• Typically, these symptoms resolve once the treatment is stopped.
• However, it's important to note that some patients may experience a recurrence of symptoms if they are rechallenged with the same drug or another bisphosphonate.
• Therefore, it's best to avoid using bisphosphonates in patients who have a history of experiencing these symptoms while on bisphosphonate therapy.

Fracture risk

• In patients with Paget's disease, it's important not to exceed the recommended dose or to use etidronate continuously for more than 6 months.
• Doing so may increase the risk of osteomalacia (softening of the bones) or fractures.
• In particular, long bones that have mostly lytic lesions (areas of bone destruction) may be prone to fracture, especially in patients who do not respond well to treatment.
• Therefore, adhering to the prescribed dosage and duration of etidronate treatment is essential to minimize the risk of fractures and other complications in patients with Paget's disease.

Irritation of the gastrointestinal mucosa

• Etidronate can irritate the upper gastrointestinal mucosa, potentially leading to conditions such as esophagitis, dysphagia, esophageal ulcers, erosions, and in rare cases, esophageal stricture.
• This risk is higher in patients who cannot follow dosing instructions properly.
• Caution should be exercised when using etidronate in individuals with conditions like dysphagia, esophageal disease, gastritis, duodenitis, or ulcers, as it may worsen these conditions.

Osteonecrosis in the jaw:

• Osteonecrosis of the jaw (ONJ), sometimes called medication-related osteonecrosis of the jaw (MRONJ), has been reported in patients taking bisphosphonates like etidronate.
• This condition is often seen after dental procedures such as tooth extractions, particularly in cancer patients receiving intravenous bisphosphonates.
• However, it can also occur in patients with osteoporosis taking oral bisphosphonates.
• Factors that increase the risk of ONJ include invasive dental treatments, cancer diagnosis, chemotherapy, radiation therapy, and certain medical conditions like anemia or infections.
• The American Association of Maxillofacial Surgeons (AAOMS) recommends considering discontinuing bisphosphonate therapy before invasive dental procedures, especially in patients taking bisphosphonates for over 4 years or those also using corticosteroids or antiangiogenic medications.
• However, there's no clear evidence that stopping oral bisphosphonates reduces ONJ risk after tooth extraction.
• If ONJ develops during therapy, care by an oral surgeon is recommended, and discontinuing bisphosphonate therapy may be considered based on individual risk and benefit assessment.

Enterocolitis

• Etidronate should be used cautiously in patients with enterocolitis (inflammation of the intestines), as diarrhea has been reported at high doses.
• In some cases, it may be necessary to withhold therapy if diarrhea occurs.
• Monitoring for symptoms of enterocolitis and adjusting treatment accordingly is important to ensure the safety and effectiveness of etidronate in these patients.

Renal impairment

• Etidronate should be used with caution in patients with renal impairment (reduced kidney function).
• Monitoring kidney function and adjusting the dosage accordingly may be necessary to ensure the safe use of etidronate in these patients.

Etidronate: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Paget Disease Monitoring:

• Alkaline Phosphatase Levels:
  • Check at 6 to 12 weeks after starting treatment to assess initial response, as bone turnover should have decreased substantially by this time.
  • Consider rechecking at 6 months to ensure maximal suppression of high bone turnover.
  • After completing treatment, monitor at approximately 6- to 12-month intervals.
• Biochemical Markers of Bone Turnover:
  • Generally, specific markers like serum P1NP, NTX, or serum beta-CTx are only necessary in patients with Paget disease who have abnormal liver or biliary tract function, or when an early assessment of treatment response is needed, such as in cases of spinal compression or very active disease.
• Pain Assessment:
  • Regularly assess the patient's pain levels to monitor response to treatment.
• Serum Calcium and 25(OH)D:
  • Monitor serum calcium levels to ensure they remain within normal range.
  • Also, check 25-hydroxyvitamin D levels periodically to assess vitamin D status, which is important for bone health.

How to administer Etidronate (Etibon)?

• Timing:
  • Take the tablet on an empty stomach, at least 2 hours before eating.
• Fluid Intake:
  • Swallow the tablet with a full glass of plain water, about 6 to 8 ounces.
• Posture:
  • After taking the medication, remain upright and avoid lying down for at least 2 hours.
• Dividing Dose:
  • If gastrointestinal discomfort happens, consider dividing the dose as advised.

Mechanism of action of Etidronate (Etibon):

• Etidronate works by reducing bone resorption, which is the process where osteoclasts break down bone tissue.
• It does this by inhibiting osteoclastic osteolysis, the process where bone cells break down bone minerals and collagen.
• By decreasing mineral release and collagen breakdown in bone, etidronate helps to maintain bone density and strength.

Onset of Action:

• It typically takes 1 to 3 months to see the effects of etidronate after starting treatment.

Duration:

• Effects can last for up to 12 months even without continuous therapy.

Absorption:

• Etidronate is poorly absorbed, with approximately 3% of the administered dose being absorbed into the bloodstream.

Metabolism:

• There is no significant metabolism of etidronate in the body.

Half-life Elimination:

• The half-life of etidronate, which represents the time it takes for half of the drug to be eliminated from the body, ranges from 1 to 6 hours.

Excretion:

• Etidronate is primarily excreted through urine, with about 50% of the drug being eliminated unchanged. Some of the drug may also be excreted in the feces as unabsorbed drug.

International Brand Names of Etidronate:

• Etibon
• Etidron
• Etidronat Jenapharm
• Etronel
• Oestrodidronel
• Osbone
• Ostedron
• Osteotop
• Osteum
• Yilin
• ACT Etidronate
• APO-Etidronate
• CO Etidronate
• MYLAN-Etidronate
• Bonatronil
• Dainol
• Didronat
• Didronate
• Didronel
• Difosfen
• Dinol
• Diosfen
• Diphos
• Disonate

Etidronate Brand Names in Pakistan: