SaO015
INTERVENTIONS FOR PREVENTING BONE DISEASE IN KIDNEY TRANSPLANT RECIPIENTS: COCHRANE SYSTEMATIC REVIEW Free

INTRODUCTION AND AIMS: Patients with CKD develop changes in bone structure, strength, and metabolism. Children experience bone deformity, pain, and delayed or impaired growth. Adults experience limb and vertebral fractures, avascular necrosis and pain. The fracture risk after kidney transplantation is four times that of the general population and may reduce quality of life, and increase pain, and disability. An earlier Cochrane systematic review published in 2007 found low certainty evidence for treatment to prevent bone complications after kidney transplantation. The aim of this systematic review was to update the evidence to include more recent trials.

METHODS: This updated Cochrane systematic review and meta-analysis of randomized controlled trials evaluated the benefits and harms of interventions for bone disease after kidney transplantation. We searched the Cochrane Kidney and Transplant specialized register up to June 2017. Risk of bias was evaluated using the Cochrane tool. Evidence certainty was evaluated using GRADE.

RESULTS: Fifty-three studies (3091 participants) were eligible. Treatments included bisphosphonates, vitamin D compounds, teriparatide, denosumab, cinacalcet, parathyroidectomy, and calcitonin. Median duration of follow-up was 12 months. Nearly all (n=41) studies evaluated bone density or bone-related biomarkers, with more recent studies evaluating proteinuria and hyperparathyroidism. Bisphosphonate therapy was usually commenced in the perioperative transplantation period (within 3 weeks) and regardless of bone mineral density. Risks of bias were generally high or unclear leading to lower certainty in the results. A single study reported outcomes among 60 children and adolescents. Studies were not designed to measure treatment effects on fracture, mortality or cardiovascular outcomes, or graft loss.Compared to placebo, bisphosphonate therapy administered over 12 months in transplant recipients prevents fracture (relative risk [RR] 0.62, 95% confidence interval [CI] 0.38 to 1.01; low certainty evidence) although the 95% confidence interval included the possibility that bisphosphonate therapy might make little or no difference. Fracture events were principally vertebral fractures identified during routine radiographic surveillance. It was uncertain whether any other drug class decreased fracture (low or very low certainty evidence). Bisphosphonate therapy may reduce bone pain (RR 0.20, 95% CI 0.04-0.93; low certainty evidence), while it was very uncertain whether bisphosphonates prevent spinal deformity or avascular bone necrosis (very low certainty evidence). Bisphosphonates may lead to hypocalcaemia (RR 5.59, 95% CI 1.00-31.1; low certainty evidence). It was uncertain whether vitamin D compounds had any effect on skeletal, cardiovascular, mortality, or transplant function outcomes (very low certainty or absent evidence). Evidence for the benefits and harms of all other treatments was of very low certainty.

CONCLUSIONS: Bisphosphonate therapy may reduce fracture and bone pain after kidney transplantation, however low certainty in the evidence indicates it is possible that treatment may make little or no difference. It is uncertain whether bisphosphonate therapy or other bone treatments prevent other skeletal complications after kidney transplantation.