Prolonged Efficacy of a Single Dose of the Bisphosphonate Zoledronic Acid

• Published in: Clinical cancer research 2007-09, Vol.13 (18), p.5406-5410
• Main Authors: BROWN, Janet E, ELLIS, Susan P, LESTER, James E, GUTCHER, Sandra, KHANNA, Tina, PUROHIT, Om-Prakesh, MCCLOSKEY, Eugene, COLEMAN, Robert E
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Adult; Aged; Antineoplastic agents; Biological and medical sciences; Bisphosphonate; Bone and Bones - diagnostic imaging; Bone Density; Bone Density Conservation Agents - administration & dosage; Bone Diseases, Metabolic - diagnostic imaging; Bone Diseases, Metabolic - drug therapy; Bone Diseases, Metabolic - etiology; Breast cancer; Cancer treatment–induced bone loss; Diphosphonates - administration & dosage; Female; Humans; Imidazoles - administration & dosage; Male; Medical sciences; Middle Aged; Neoplasms - complications; Osteoporosis; Pharmacology. Drug treatments; Zoledronic acid
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-0247

Purpose: Bisphosphonates play a central role in the management of bone loss due to a range of disorders, including metastatic bone disease, cancer treatment–induced bone loss, and postmenopausal osteoporosis. With potent bisphosphonates, such as zoledronic acid, it may be possible to maintain efficacy with relatively infrequent administration. Experimental Design: Sixty-six patients who were osteopenic at >1 year following curative cancer therapy received a single i.v. 4 mg dose of the bisphosphonate zoledronic acid. Bone mineral density (BMD) was measured using double-beam X-ray absorptiometry scan and the bone resorption marker N-telopeptide of type II collagen was determined using a chemiluminescence ELISA assay. Results: The single dose of zoledronic acid induced mean increases in bone BMD at the lumbar spine of 3.1%, 5.2%, and 5.3% and at the total hip of 2.7%, 3.5%, and 4.3% after 12, 24, and 36 months of follow-up, respectively ( P < 0.001 at all time points). By 36 months, 84% of patients had achieved increase in BMD at the spine and 90% at the hip. The mean percentage decrease in the bone resorption marker N-telopeptide was ∼58% at 6 weeks and 42%, 33%, and 31% at 12, 24, and 36 months, respectively ( P < 0.001). Conclusions: A single dose of zoledronic acid in patients with low BMD results in a sustained increase in BMD and a corresponding decrease in bone resorption. Very infrequent administration of zoledronic acid may have clinical benefits in terms of convenience, reduced toxicity, improved compliance, and cost.