Interventions for preventing bone disease in kidney transplant recipients: A systematic review of randomized controlled trials

Background: Before renal transplantation complex abnormalities of bone metabolism exist and lead to increased risk for fracture after transplantation. This study was conducted to assess the evidence available to guide targeted treatment to reduce bone disease in transplant recipients. Methods: The Cochrane CENTRAL Registry, MEDLINE, and EMBASE were searched for randomized trials of interventions for bone disease after renal transplantation. Data were extracted on fracture, bone mineral density (BMD) by means of dual-energy X-ray absorptiometry, acute graft rejection, and adverse events. Analysis was performed with a random-effects model, and all results are expressed as relative risk with 95% confidence intervals (CIs). Results: Twenty-three eligible trials (1,209 patients) were identified. No trial found a reduction in risk for fracture. Bisphosphonates (7 trials; 268 patients; weighted mean difference [WMD], 7.66; 95% CI, 4.82 to 10.50), vitamin D analogues (2 trials; 51 patients; WMD, 6.13; 95% CI, 4.97 to 7.29), and calcitonin (1 trial; 31 patients; WMD, 5.00; 95% CI, 0.88 to 9.12) favorably affected the percentage of change in BMD at the lumbar spine compared with no treatment. Bisphosphonates (4 trials; 149 patients; WMD, 7.18; 95% CI, 6.22 to 8.13) and vitamin D analogues (2 trials; 51 patients; WMD, 3.73; 95% CI, 2.71 to 4.75), but not calcitonin (1 trial; 31 patients; WMD, −0.30; 95% CI, −5.00 to 4.40), had a favorable effect on BMD measured at the femoral neck compared with no treatment. The incidence of reported toxicity was low. Conclusion: The trials were inadequately powered to show a reduction in risk for fracture. Bisphosphonates and vitamin D have a beneficial effect on BMD at the lumbar spine and femoral neck. With increasing survival after renal transplantation, this study stresses the importance of randomized controlled trial evidence of interventions of bone disease after renal transplantation.