Zoledronic Acid for the Prevention of Bone Lesions in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS).

Recent studies have shown that approximately 5% of individuals over the age of 70 years have a monoclonal gammopathy and are at high risk for developing myeloma or a related lymphoproliferative disorder. Patients with monoclonal gammopathy of undetermined significance (MGUS) are at high risk for developing new fractures, particularly vertebral compression fractures. Currently, there is no treatment for this patient population. Among patients with advanced multiple myeloma, zoledronic acid has demonstrated efficacy in reducing skeletal complications. Therefore, a multicenter phase II trial is ongoing to evaluate zoledronic acid for patients with MGUS and a high risk for fractures. A total of 80 patients with MGUS and a T-score of less than −1.0 who have not received intravenous bisphosphonates within the past 2 years or oral bisphosphonates for more than 3 months within the past 2 years are eligible for enrollment. Eligible patients may not have had a change in hormonal therapy within 6 months of study entry. Patients will receive 4 mg zoledronic acid infused over 15 minutes at 0, 6, and 12 months. The primary endpoint is the change in bone mineral density (BMD) in the lumbar spine 1 month following the last infusion of zoledronic acid. Secondary endpoints include the mean change from baseline hip BMD, number of patients with new fractures, changes in serum M protein levels, number of patients who develop myeloma or other related malignancies, and safety of zoledronic acid in this patient population. The study commenced recruitment in 2004 and has enrolled 52 patients to date. Enrollment is continuing and expected to be complete by the end of 2006. This study may provide further support for the use of zoledronic acid in patients with MGUS who are at high risk for fracture development and currently do not receive any treatment.