Zoledronic acid prevents bone loss after liver transplantation - A randomized, double-blind, placebo-controlled trial

Background: Clinically important rapid bone loss occurs within 3 to 6 months after liver transplantation and may be associated with osteoporotic fractures. Objective: To determine whether bisphosphonate treatment with zoledronic acid reduces transplant-related bone loss more than placebo in adults having liver transplantation for chronic liver disease. Design: 12-month randomized, double-blind, placebo-controlled trial. Setting: 2 large liver transplantation centers in Australia. Patients: 62 adults having liver transplantation for chronic liver disease. Interventions: Infusions of zoledronic acid, 4 mg (n = 32), or saline (n = 30) were given within 7 days of transplantation and again at months 1, 3, 6, and 9 after transplantation. All patients received supplementation with calcium carbonate, 600 mg/d, and ergocalciferol, 1000 U/d. Measurements: The primary outcome was bone mineral density (BMD) measured by dual x-ray absorptiometry before transplantation and 3, 6, and 12 months later. Secondary outcomes included bone turnover markers that were measured before transplantation and 1, 3, 6, 9, and 12 months later. Results: There were statistically significant interactions between treatment effects and time for BMD measurements at the lumbar spine (P = 0.002), femoral neck (P = 0.001), and total hip (P < 0.001). Differences in acute bone loss 3 months after transplantation favored zoledronic acid over placebo. Differences between groups in percentage change from baseline adjusted for baseline weight and serum parathyroid hormone (PTH) level were 4.0% (95% Cl, 1.1 % to 7.0%) for the lumbar spine, 4.7% (Cl, 1.9% to 7.6%) for the femoral neck, and 3.8% (Cl, 1.7% to 6.0%) for the total hip. At 12 months after transplantation, the difference in percentage change from baseline between the 2 groups adjusted for baseline weight and serum PTH level was 1.1 % (Cl, -2.1% to 4.4%) for the lumbar spine, 2.7% (Cl, 0.0% to 5.4%) for the femoral neck, and 2.4% (Cl, 0.1% to 4.7%) for the total hip. Treatment with zoledronic acid induced temporary secondary hyperparathyroidism and postinfusion hypocalcemia statistically significantly more often than did placebo. Limitations: The trial was not powered to assess fractures, and 10 of 62 (16%) patients were not included in adjusted analyses because of missing weight or serum PTH measurements. Conclusion: Treatment with zoledronic acid can prevent bone loss within the first year after liver transplantation.