Zoledronic Acid for Paget’s Disease

The FDA has approved the use of zoledronic acid 5 mg (Reclast®) for the treatment of Paget’s disease, a condition in which excessive osteoclastic bone resorption produces irregular formation of new bone. Patients with Paget’s disease often suffer from bone pain, deformity, or fracture, as well as reduced mobility and quality of life. Now, the approval of zoledronic acid for Paget’s provides patients with their first new therapeutic option in almost 10 years.

Like other bisphosphonate drugs, zoledronic acid inhibits osteoclast-mediated bone resorption; however, it may offer some advantages with respect to ease of use. Zoledronic acid is given as a single 15-minute infusion, whereas most other bisphosphonates are administered orally for up to 6 months. In addition, patients receiving oral bisphosphonates are asked not to eat prior to drug administration (to allow for sufficient absorption of the drug from the digestive tract) and not to lie down for up to 1 hour after drug administration (to reduce the risk of upper GI irritation). Neither of these restrictions is required in patients receiving zoledronic acid. Key considerations for the infusion of zoledronic acid are shown in the accompanying table.

Table. Infusion of zoledronic acid
Prior to infusion:

• Appropriate laboratory tests should be performed, including those assessing kidney function (confirm creatinine clearance >35 mL/min), serum alkaline phosphatase (ALP), and calcium levels.
• Patients should take calcium (1500 mg/day in divided doses) and vitamin D (800 IU/day) supplements, and need to drink sufficient fluids immediately prior to the infusion to make sure they are adequately hydrated.

At the time of infusion, the healthcare provider should:

• Explain the infusion procedure to the patient
• Check the patient’s vital signs
• Follow standard and safe sterile techniques and intravenous (IV) procedures
• First gain IV access with an extension set before spiking the bottle (rather than priming the IV line with zoledronic acid)
• Check that the IV line is secure and not leaking
• Use a vented line with a constant infusion rate of 100 drops/min (based on a tubing drop factor of 15 drops/mL) to achieve an infusion that takes at least 15 minutes
• Help the patient remain comfortable during the infusion
• Confirm that the patient (or caregiver) understands the importance of continuing use of daily vitamin D and calcium supplements for prevention of hypocalcemia, particularly during the first 2 weeks after infusion
• Explain that flu-like symptoms such as muscle aches, headaches, chills, and nausea can occur during the first 2 or 3 days after the infusion, and that these symptoms can be alleviated with appropriate medication (eg, acetaminophen, non-steroidal anti-inflammatory drugs)
• Arrange to meet the patient again in 3 months to check ALP levels

The safety and efficacy of a 4-mg dose of zoledronic acid has already been established in oncology indications (for which it is marketed as Zometa®), and data from two 6-month clinical trials have provided evidence for benefits in patients with Paget’s disease. In these randomized, double-blind studies, patients received either an oral dose of 30 mg risedronate for 60 days or a single infusion of zoledronic acid 5 mg. An analysis of pooled data from the studies found that a therapeutic response was achieved in 96% of patients in the zoledronic acid group, as compared with 74% in the risedronate group. The adverse events most frequently observed in the zoledronic acid group included pain in joints, bone, and muscles; nausea; headache; fatigue; and flu-like symptoms (including chills and fever). These events typically occurred during the first 3 days after infusion and resolved within 3 days. Zoledronic acid was also recently approved as a once-yearly treatment for postmenopausal women with osteoporosis.

Submitted by Betsy McClung, MN RN, member of the Board of Directors for the Paget Foundation and Jacques Brown, MD, member of the Paget’s Foundation Advisory Medical Panel.