MGUS occurs in 5% of individuals over 70 yrs of age and these pts have been found to have increased rates of bone resorption. Osteoporosis associated with MGUS have higher bone resorption compared to sex and aged-matched pts with osteoporosis but without evidence of MGUS. Not only do pts with MGUS have a higher prevalence of osteopenia/osteoporosis than the normal population but they also have an increased risk of fractures (fx). ZOL has been shown to increase BMD in the treatment of gonadotropin agonist-induced osteoporosis in men with prostate cancer without metastatic bone disease when administered every 3 mos at 4 mg. The rationale for the use of ZOL for pts with osteopenia/osteoporosis in the setting of MGUS is based on these studies coupled with the knowledge that pts with this disorder have a higher prevalence of bone loss and fx risk. To date, no agents have been formally studied in the treatment of osteopenia/osteoporosis associated with MGUS. A schedule of 4 mg every 6 mos has been shown to be safe and effective in increasing BMD for other cancer pts without metastatic bone disease but with significant bone loss. This open-label study was designed to evaluate the efficacy and safety of this dose and schedule of ZOL for MGUS pts with significant loss of bone. Pts had to have osteopenia/osteoporosis (T-score worse than -1) as verified by a DEXA scan and a diagnosis of MGUS. Pts with prior use of oral bisphosphonates (BIS) or fluorides for more than three mos within the last two yrs or prior use of intravenous (IV) BIS within the last two yrs were excluded. ZOL at 4 mg was administered IV at 0, 6, and 12 mos. To assess the efficacy of ZOL therapy, DEXA scans and skeletal surveys were conducted at screening and one mo after the final ZOL infusion (13 mos). Fifty-four pts were enrolled on this trial with an average age of 68 (range, 50 to 91 yrs). The starting L-spine T-scores ranged from −3.97 to −1.10 (mean = −2.16). After one year of ZOL therapy, T-scores improved by a mean of +0.55 (range, −0.40 to +3.90; P = 0.0042). This corresponded to a mean increase in BMD of +25.5% (range, −19.0% to +134%). Similar evaluation in the hip showed baseline T-scores of −3.50 to −1.00 (mean = −1.88). The mean change in T-score was +0.27 (range, −0.60 to +2.00; P = 0.0046) corresponding to a mean increase of +14.4% (range, −54.5% to +163%). One pt developed chronic lymphocytic leukemia while on study whereas no other pt showed progression to myeloma or a related B-cell disorder. No pt developed osteonecrosis of the jaw or a significant adverse renal event. During the study, no pt developed a new fx. This trial suggests that ZOL administered at 4 mg every 6 mos significantly improves BMD in MGUS pts with bone loss (osteopenia/osteoporosis); and, thus, suggests that this is a safe and effective treatment to prevent the development of new fxs in this high risk population.
Disclosure: Consultancy: Novartis. Research Funding: Novartis. Honoraria Information: Novartis. Membership Information: Novartis.