What Is Zometa?
Zometa® (zoledronic acid) is a medication known as a bisphosphonate that prevents bone damage in multiple myeloma patients. Our body closely controls cells that build bone (osteoblasts) and cells that break down bone (osteoclasts). For myeloma patients, signals sent by myeloma cells can disturb cell control by stimulating osteoclasts, leading to excess bone breakdown. Myeloma patients may experience various bone problems, including weak bones, lytic lesions (destruction of an area of bone), and fractures or breaks in the bone.
Experts from the International Myeloma Working Group recommend Zometa as the preferred targeted treatment in patients with newly diagnosed myeloma, whether or not they are diagnosed with bone disease.1
In addition to preventing bone damage, research suggests that Zometa may also have an antimyeloma effect. In the Myeloma IX trial of studying bisphosphonate and thalidomide-based therapy in 1,970 patients, Zometa improved progression-free survival by about two months and reduced mortality by about 5.5 months compared to clodronic acid.2,3
Who Is a Candidate for Zometa?
Zometa may be recommended for myeloma patients, even if you do not have current bone disease. Zometa is the preferred bone-targeted treatment in patients with newly diagnosed myeloma, except in certain circumstances, such as patients with impaired kidney function.4 If you have kidney impairment, your doctor may offer another medication, such as Xgeva® (denosumab).
Hypocalcemia or low calcium levels in your blood must be corrected before starting treatment with Zometa. Your doctor will do a blood test to measure your calcium levels before starting treatment. Depending on the results, your doctor may recommend taking calcium and vitamin D supplements. Calcium and vitamin D are often given as pills to take at home.
You may not be eligible to take Zometa if you are pregnant, as Zometa can cause harm to a developing unborn baby.
There are other reasons you may not be a candidate for Zometa. Please see the package insert for more information and discuss Zometa with your doctor.
How Is Zometa Given?
Zometa is administered monthly by an IV infusion. The standard dose is 4 mg infused during 15–45 minutes. Toxicities associated with Zometa are related to dosage, frequency of administration, and duration of infusion. Therefore, your doctor may recommend to reduce your dose and/or frequency of administration, and/or increase the duration of infusion.
What Are Potential Side Effects and Concerns with Taking Zometa?
The kidney toxicity-related concern with the use of Zometa is an increase in serum creatinine. Reports of both increased serum creatinine and occasionally more severe kidney damage called acutetubular necrosis (ATN) have raised questions if Zometa must be used more cautiously to minimize the potential for kidney-related problems.
Your serum creatinine level should be checked before each dose of Zometa, especially if there is concern about kidney function, such as with Bence-Jones myeloma, diabetes, long-standing high blood pressure, and in elderly or frail patients.
If you had normal renal (kidney) function at the outset, and your serum creatinine value increases by 0.5 mg/dL, or if you had abnormal renal function at the outset, and your serum creatinine value increases by 1.0 mg/dL, your doctor should hold the next dose of Zometa until your
serum creatinine value returns to within 10% of the baseline.
If you experienced a mild elevation in serum creatinine value, which then returns to within 10% of the baseline, your doctor may consider adjustments to your treatment schedule, such as increasing the time of infusion from 15 minutes to 30 minutes or more, using a larger volume of diluting fluids, or delaying the administration of the next dose. Ask your doctor which option is most appropriate for your individual case.
The Z-MARK clinical trial, conducted from 2007 through 2012 at 67 centers in the U.S., evaluated the effectiveness and safety of a dosing method for Zometa in preventing skeletal complications in121 patients with advanced myeloma who were on an IV bisphosphonate for about 1–2 years. Participants received the standard dose or a reduced dose of Zometa every 4 weeks or every 12 weeks for up to 96 weeks. Participants in the “every 12 weeks” group who experienced a skeletal-related event (SRE) were switched to the “every 4 weeks” group.
Study results published in 2016 showed that “the use of Zometa every 12 weeks compared with every 4 weeks did not result in an increased risk of skeletal events over 2 years.”
Zometa Side Effects With Multiple Myeloma
The updated ASCO guidelines state that “for patients without active myeloma who are receiving maintenance therapy, receiving bisphos phonates every 3 months, rather than monthly, is an option.” The guidelines note that “there are insufficient data to recommend a specific duration of bisphosphonate therapy” beyond 2 years. Monthly treatment is to be resumed “upon relapse with new-onset SREs.”
Zometa may cause severe reactions in some people. When studied in newly diagnosed myeloma patients, the most common side effects were:
- gastrointestinal effects (such as diarrhea, nausea, constipation, loss of appetite),
- back pain,
- fatigue,
- fever,
- low levels of red blood cells (anemia),
- low levels of platelets (thrombocytopenia),
- low levels of a type of immune cell called neutrophils (neutropenia),
- low levels of potassium (hypokalemia),
- low levels of phosphorus (hypophosphatemia),
- and low levels of calcium (hypocalcemia).
The most common serious side effects were pneumonia and sepsis (a life-threatening infection)5.
Like other bone-targeting medications, Zometa may cause osteonecrosis of the jaw (ONJ). Therefore, you must complete a dental exam before starting Zometa. ONJ may cause you to feel:
- pain,
- numbness,
- unusual drainage,
- or swelling from your jaw, mouth, or teeth.
If you experience any of these symptoms while taking Zometa, it is important to contact your doctor
For a complete list of side effects, please see the Zometa package insert or check out the additional resources below.
Additional Information
- Stenger, “Updated Recommendations on the Treatment of Multiple Myeloma–Related Bone Disease From the Bone Working Group of the International Myeloma Working Group - The ASCO Post.”
- Raje et al., “Denosumab versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma.”
- Morgan et al., “Long-Term Follow-up of MRC Myeloma IX Trial.”
- Stenger, “Updated Recommendations on the Treatment of Multiple Myeloma–Related Bone Disease From the Bone Working Group of the International Myeloma Working Group - The ASCO Post.”
- Raje et al., “Denosumab versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma.”
The International Myeloma Foundation medical and editorial content team
Comprised of leading medical researchers, hematologists, oncologists, oncology-certified nurses, medical editors, and medical journalists, our team has extensive knowledge of the multiple myeloma treatment and care landscape.
Additionally, the content on this page is medically reviewed by myeloma physicians and healthcare professionals.
Last Medical Content Review: February 11, 2025