Effect of neridronate in osteopenic patients after heart, liver or lung transplant: a multicenter, randomized, double-blind, placebo-controlled study.

ABSTRACT

BACKGROUND: Transplantation (Tx) is an effective therapeutic option in patients with end-stage organ failure and osteoporosis and related fractures are a recognized complication in these patients. Aim of this study was to evaluate the efficacy of neridronate in patients with reduced bone mass after Tx of the heart, liver or lung. METHODS: In this multicenter randomized double-blind controlled trial (RCT), 22 patients were treated with neridronate (25 mg i.m./month) and 17 received placebo. All patients received daily oral calcium (500 mg) and vitamin D (400 IU). Dual-energy X-ray absorptiometry (DXA) was evaluated at 0, 6 and 12 months and markers of bone turnover at 0, 3, 6, 9 and 12 months. RESULTS: Thirty-nine patients (11 heart Tx, 21 liver Tx, 7 lung Tx), aged 49.3±9.1 years, with a T-score <-2.0 SD at lumbar spine or femoral level were included. In neridronate-treated patients, a significant increase in lumbar bone mineral density (BMD) was observed after 12 months vs. placebo control (0.92±0.13 g/cm2 vs. 0.84±0.08 g/cm2; P=0.005). Femur and hip BMD remained unchanged between groups. Total alkaline phosphatase, bone alkaline phosphatase and beta-cross-laps significantly decreased over the 12 months in neridronate-treated patients vs. placebo, respectively (107.4±74 U/L vs. 157.6±107.1 U/L, P=0.002; 5.7±3.3 µg/L vs. 11.7±4.3 µg/L, P<0.001 and 0.25±0.13 ng/mL vs. 0.73±0.57 ng/mL, P<0.001). No difference was observed between neridronate and placebo groups regarding safety profile. CONCLUSIONS: This is the first RCT that demonstrates the efficacy of neridronate in increasing bone density and reducing bone turnover in organ Tx recipients with significant skeletal morbidity.