Zoledronic Acid

Zoledronic acid (zoledronate) is a drug that prevents the breakdown of bone and is used to treat complications affecting bone in prostate and breast cancers. Zoledronic acid is also useful for treating osteoporosis in postmenopausal women. Painful deterioration of the jaw bone has been reported during zoledronic acid use, mainly in patients with cancer who are undergoing dental surgery. It is sold under several brand names, including Zometa, Zomera, Reclast, and Aclasta. It is marketed by Novartis Pharmaceutical Corporation. The Food and Drug Administration (FDA) approved its use in August 2000.

Structure of zometa. Source: Wikimedia Commons

Other Names

• Zometa
• Zomera
• Reclast
• Aclasta

Uses/Indications

Zoledronic acid is used to reduce high blood levels of calcium (hypercalcemia) caused by cancerous tumors. It is also used to prevent painful metastasis (spread) of prostate or breast cancers to bone. In patients with multiple myelomaor solid tumors, it is used to strengthen bone.

Reclast is used to treat the abnormal bone growth in Paget disease. It is also approved to treat osteoporosis (bone softening) during postmenopause.

How Zoledronic Acid is Taken

Zoledronic acid is given as an 4-mg intravenous (IV) infusion. The infusion lasts at least 15 minutes, and the treatment is repeated every three to four weeks.

A 5-mg dose of zoledronic acid, in the Reclast formulation, is given once to patients with Paget disease and every year in women during menopause at risk for osteoporosis.

How Zoledronic Acid Works

Bone is continuously being remodeled, or recycled, by cells called osteoblasts and osteoclasts. Osteoclasts break down and resorb bone, allowing osteoblasts to lay down new bone in the resorption cavity. As the osteoclast resorbs bone, calcium is released into the blood. If bone remodeling is uncontrolled, as it sometimes is after menopause, bones can become weakened and more likely to fracture.

Zoledronic acid belongs to a class of drugs called bisphosphonates. These drugs bind to bone and inhibit the activity of osteoclasts. In this way, they reduce the breakdown of bone. This reduced resorption lowers the level of calcium released from bone and tends to strengthen existing bone.

How the Body Affects Zoledronic Acid

The body does not alter, or metabolize, zoledronic acid. Instead, the drug is excreted unchanged in the urine. Zoledronic acid can be given every few weeks because it is removed very slowly from the body. The half-life of zoledronic acid, or the time it takes for the concentration in the blood to be reduced by half, is about six days.

Side Effects

Below are some common side effects of zoledronic acid:

• back and bone pain
• fever
• flu-like symptoms consisting of fever, chills, and bone, joint or muscle pain
• nausea and vomiting
• itching
• chest pain
• low blood levels of magnesium, phosphorus, and calcium
• fainting

These side effects are usually mild and of short duration. Some rare side effects include kidney dysfunction, inflammation in the eye and redness and swelling at the injection site.

Risks and Precautions

Like many bisphosphanates, zoledronic acid may reduce kidney function. This risk is increased in the following situations:

• doses higher than 4 mg every three to four weeks
• dehydration
• co-administration of drugs that harm the kidney (e.g., gentamycin (Garamycin))
• pre-existing kidney failure

In fact, extreme caution is used in patients with pre-existing kidney damage, and often the dose needs to be adjusted in these individuals.

Painful deterioration of the jaw bone, called osteomalacia, has been reported during use of bisphosphonates, including zoledronic acid. Most often this has occurred in patients who were taking steroids and cancer chemotherapy while undergoing dental surgery.

Complications are more likely in patients with an allergy to acetylsalicylic acid (Aspirin), or to other bisphosponates, including zoledronic acid itself. Asthma also increases the risk for complications.

Zoledronic acid may exacerbate conditions of low magnesium, phosphate, and calcium. Dangerously low calcium levels are morel likely in patients with hypoparathyroidism (low activity of the parathyroid) and those with prior thyroid surgery.

Zoledronic acid may harm the fetus and is not given during pregnancy unless the excessive calcium is life-threatening. Nursing an infant is avoided during treatment.

Drug Interactions

The risk of abnormally low calcium levels is increased if zoledronic acid is taken with “water pills” called loop diuretics (e.g., furosemide (Lasix)).

Toxicity to the kidney may result from the concomitant use of zoledronic acid with non-steroidal anti-inflammatory drugs (NSAIDs), aminoglycoside antibiotics, and thalidomide (Thalomid). Indeed, some cases of kidney toxicity have been reported during treatment with both thalidomide and zoledronic acid. However, a study of 24 patients with myeloma receiving both drugs did not find an increased risk of kidney dysfunction over 16 months of treatment.^[1]

Supplements containing high amounts of magnesium, calcium, or phosphorus may also interact with zoledronic acid.

Research

Zoledronic acid reduces the pain associated with the spread of prostate or breast cancer to bone. In a study of over 400 patients with prostate cancer given either zoledronic acid or placebo, a favorable response in pain relief was seen in 33% and 25% of patients given the drug and placebo, respectively.^[2]

Zoledronic acid improves bone mineral density (a measure of bone strength) and bone turnover (a measure of bone formation and resorption) in postmenopausal women. The increased bone strength can reduce the risk of fracture. A study of postmenopausal women found that two doses of zoledronic acid (given once a year) reduced the risk of developing a fracture in the vertebrae by 70%. ^[3] Zoledronic acid reduced the risk of hip fracture by 41%.

References

1. ↑ Spencer A, Roberts A, Kennedy N, et al. Renal safety of zoledronic acid with thalidomide in patients with myeloma: a pharmacokinetic and safety sub-study. BMC Clin Pharmacol. 2008 Mar 31;8:2. Full Text
2. ↑ Weinfurt KP, Anstrom KJ, Castel LD, Schulman KA, Saad F. Effect of zoledronic acid on pain associated with bone metastasis in patients with prostate cancer. Ann Oncol. 2006 Jun;17(6):986-9. Abstract | Full Text
3. ↑ Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.] N Engl J Med. 2007 May 3;356(18):1809-22. Full Text

External Links

Novartis Oncology: Zometa