Zolendronic acid, annual bisphosphate

Zoledronic acid is indicated for the treatment of hypercalcemia of malignancy, bone lesions associated with multiple myeloma and bone metastases from solid tumors, osteoporosis in postmenopausal women, and Paget's disease of bone.

Osteoporosis

In a 3-year, randomized, double-blind, placebo-controlled study of postmenopausal women with evidence of osteoporosis (n=7765), annual intravenous infusions of zoledronic acid were superior to placebo in reducing the risk of vertebral, hip, and other types of fractures.(Black et al, 2007)

A single-intravenous dose of zoledronic acid was noninferior to once daily oral risedronate for the prevention and treatment of glucocorticoid-induced osteoporosis in the multicenter, randomized, double-blind, double-dummy Health Outcomes and Reduced Incidence with Zoledronic acid Once yearly (HORIZON) trial (n=833). (Reid et al, 2009).

Paget Disease

Zoledronic acid, administered as a single intravenous infusion, produced a quicker, more complete and sustained responses in Paget's disease (osteitis deformans) compared to daily oral treatment with risedronate.(Reid et al, 2005).

Malignancy (vs Pamidronate)

Direct comparisons with pamidronate in patients with hypercalcemia of malignancy have shown greater response rates and extended relapse times with zoledronic acid in clinical trials (Major et al, 2001). However, direct comparisons with other bisphosphonates, including alendronate and ibandronate are needed to determine if zoledronic acid offers any significant advantages in either clinical efficacy or safety.

An expert panel from the American Society of Clinical Oncology recommends intravenous pamidronate or intravenous zoledronic acid as a supportive benefit to multiple myeloma patients. The panel also recommends initiating these agents for patients with pain due to osteolytic disease and as adjunctive treatment for patients receiving radiation therapy, analgesics, or surgical intervention to stabilize fractures or impending fractures (Berenson et al, 2002).

Intravenous zoledronic acid and pamidronate were similarly efficacious when used to treat osteolytic and mixed-bone metastases arising from advanced breast cancer (stage IV, with at least 1 metastatic lesion) or multiple myeloma(Rosen et al, 2001).

Zoledronic acid induced higher rates of response compared with pamidronate when used to treat hypercalcemia of malignancy . Fever, anemia, nausea, constipation, and dyspnea were the adverse events most commonly reported, occurring at similar frequencies among patients receiving either zoledronic acid or pamidronate (Major et al, 2001).

Monitoring Parameters:

• biochemical markers of bone formation/resorption
• radiologic evidence of fracture
• serum calcium (albumin-adjusted)
• standard hypercalcemia-related metabolic parameters
• oral examination by the prescriber prior to treatment; a dental examination in patients at risk for osteonecrosis of the jaw (cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene, pre-existing dental disease or infection, anemia, coagulopathy)
• periodic dental exam for signs of osteonecrosis of the jaw
• hemoglobin and hematocrit
• signs and symptoms of incapacitating bone, joint, and/or muscle pain (common as it will appear within few days post infusion)
• urine albumin; every 3 to 6 months
• cardiac function esp to watch out any atrial fibrillation
• monitoring serum creatinine, it is not advisable to initial in patient with CrCl <35ml/min

References:

Black DM, Delmas PD, Eastell R, et al: Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356(18):1809-1822.

Reid DM, Devogelaer JP, Saag K, et al: Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 2009; 373(9671):1253-1263.

Reid IR, Miller P, Lyles K, et al: Comparison of a single infusion of Zoledronic Acid with Risedronate for Paget's disease. N Engl J Med 2005; 353(9):898-908.

Major P, Lortholary A, Hon J, et al: Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001; 19(2):558-567

Berenson JR, Hillner BE, Kyle RA, et al: American society of clinical oncology clinical practice guidelines: the role of bisphophonates in multiple myeloma. J Clin Oncol 2002; 20:3719-3736.

Rosen LS, Gordon D, Kaminski M, et al: Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind comparative trial. Cancer J 2001; 7(5):377-387.