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Zoledronic acid: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on July 5, 2023.

1. How it works

  • Zoledronic acid strengthens bones and may be used for the treatment or prevention of osteoporosis.
  • Zoledronic acid works by inhibiting osteoclasts which are responsible for breaking down and reabsorbing bone (by a process known as bone resorption). It also inhibits increased osteoclastic activity and the release of calcium by the skeleton induced by tumors.
  • Zoledronic acid belongs to the class of medicines known as bisphosphonates.

2. Upsides

  • Zoledronic acid is used for the treatment of high calcium levels (hypercalcemia) associated with cancer.
  • Zoledronic acid (including the Zometa brand) may be used to treat patients with multiple myeloma or bone metastases from solid tumors in addition to standard chemotherapy regimens.
  • The use of zoledronic acid in non-tumor-related hypercalcemic conditions (such as hyperparathyroidism) has not been established.
  • The Reclast brand of zoledronic acid may be used to treat or prevent osteoporosis caused by menopause, steroid use, or low hormone levels due to gonadal failure. Reclast may also be used to increase bone mineral density in men and to treat Paget's disease of the bone in men and women.
  • Zoledronic acid is an injection that only requires administration every year for the treatment of osteoporosis, and every two years for the prevention of osteoporosis. It is administered every three to four weeks when used for the treatment of osteolytic bone lesions of multiple myeloma.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Fever, nausea, constipation, anemia, and shortness of breath are the most frequently reported side effects. Low blood pressure, abdominal pain, and vomiting may also occur.
  • A lowering in the levels of certain electrolytes such as phosphate, potassium, and magnesium may occur.
  • Some people report insomnia, anxiety or confusion, coughing, and skeletal pain with zoledronic acid.
  • The optimal duration of use of zoledronic acid has not been determined. Discontinuation of therapy should be considered by doctors after 3 to 5 years in patients with osteoporosis at low risk of fracture. Patients who discontinue therapy should have their risk for fracture re-evaluated periodically.
  • May not be suitable for some people including those with kidney disease, pre-existing esophageal or gastrointestinal conditions, low blood calcium levels (hypocalcemia), or dental disease. Patients who are being given zoledronic acid for high calcium levels associated with cancer should be adequately hydrated before administration. Rare reports of bronchoconstriction (a narrowing of the airways) have been reported in aspirin-sensitive patients given zoledronic acid.
  • There are concerns about the long-term safety of bisphosphonates (such as zoledronic acid) as long-term use has been associated with atypical femur fractures, osteonecrosis of the jaw, and esophageal cancer. The risk of osteonecrosis of the jaw is greater in those who have received chemotherapy, radiation, or steroids.
  • Rarely may cause other side effects including uveitis (eye inflammation) and other adverse effects. Severe and occasionally incapacitating bone joint or muscle pain has also been reported. Zoledronic acid should be discontinued if this occurs.
  • May interact with some other medicines such as aminoglycosides or calcitonin (may have an additive calcium-lowering effect), loop diuretics (may have an additive sodium-lowering effect) as well as other drugs that may also adversely affect the kidneys. Zoledronic acid should never be given at the same time as other bisphosphonates, such as Reclast.
  • Zoledronic acid is only available as an injection for administration by a healthcare provider.
  • Zoledronic acid must be administered over no faster than 15 minutes because shorter infusion times have been associated with an increased risk of renal toxicity which may progress to kidney failure.
  • Avoid in pregnancy. Bisphosphonates, such as zoledronic acid, can cause fetal harm in animals, such as renal pelvis ureter syndrome and interference with natural delivery. Animal data suggest that the uptake of bisphosphonates into fetal bone is greater than into maternal bone. There are no data on fetal risk and pregnancy in humans. It is unknown if zoledronic acid is excreted into human milk and use should be avoided.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Zoledronic acid is only available as an injection for administration by a healthcare provider. It must be administered over no less than 15 minutes but only needs to be given once a year when used for the treatment of osteoporosis and once every two years when given to prevent osteoporosis.

5. Tips

  • You may need to take supplementary calcium or vitamin D if your dietary intake is inadequate. Your doctor will advise you about this.
  • Tell your doctor if you have ever had kidney problems in the past before taking zoledronic acid.
  • Make sure you get your laboratory tests done to test for creatinine) during your zoledronic acid therapy.
  • Make sure you have a dental check-up before you start zoledronic acid. Talk to both your dentist and doctor if you require dental surgery or tooth extraction and you have been administered zoledronic acid. Keep good oral hygiene and get regular dental check-ups while you are being given zoledronic acid. Report any oral symptoms such as tooth pain, jaw pain, loose teeth, or mouth ulcers to your doctor while you are being administered zoledronic acid.
  • Tell your doctor if you experience any thigh or groin pain, muscle cramps or twitches, severe or debilitating muscle pain, eye inflammation, or any other adverse effects of concern while you are being administered zoledronic acid.
  • Do not take any other medications with zoledronic acid without first talking with your doctor. Never take other bisphosphonates (such as Reclast) while taking zoledronic acid.
  • Tell your doctor if you are sensitive to aspirin before you are administered zoledronic acid. Report any feelings of breathlessness to your doctor if they occur while taking zoledronic acid.
  • Do not take zoledronic acid while pregnant or breastfeeding. If you inadvertently become pregnant while being administered zoledronic acid, tell your doctor immediately.

6. Response and effectiveness

  • The effectiveness of zoledronic acid is comparable to most other bisphosphonates; however, because it has a very favorable dosing regimen its real-life benefits are mainly because people taking oral bisphosphonates are not very compliant.
  • After treatment with zoledronic acid, BMD increased by 11% from baseline after one year of treatment and 20.7% from baseline after two years of treatment.

7. Interactions

Medicines that interact with zoledronic acid may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with zoledronic acid. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with zoledronic acid include:

  • aminoglycoside antibiotics, such as amikacin, gentamicin, kanamycin, neomycin, paromomycin, or tobramycin
  • angiogenesis inhibitors, such as bevacizumab or everolimus
  • aspirin
  • calcitonin
  • deferasirox
  • diuretics, such as bumetanide, ethacrynic acid, or furosemide
  • digoxin
  • chemotherapy agents for cancer
  • NSAIDs, such as ibuprofen, diclofenac, and naproxen
  • oral steroids, such as dexamethasone, prednisone, and methylprednisone
  • proton pump inhibitors, such as omeprazole
  • thalidomide.

Note that this list is not all-inclusive and includes only common medications that may interact with zoledronic acid. You should refer to the prescribing information for zoledronic acid for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use zoledronic acid only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: July 5, 2023.