Interventions for preventing bone disease in kidney transplant recipients

Recipients of a kidney transplants have a pre-existing increase in bone fragility resulting from kidney disease. Bone mineral density decreases rapidly in the first year after engraftment and there is continued bone loss through the period of transplantation. The incidence of fracture following successful transplantation is greater than 2% per annum. Bone loss and fracture risk are significantly higher than both the general and dialysis population. This study examines the benefits and risks of treatments used to reduce bone disease following kidney transplantation. Twenty-four trials (12,99 patients) were included. No individual intervention (bisphosphonate, vitamin D sterol or calcitonin) has been shown in randomised controlled trials to reduce fracture risk after kidney transplantation. Meta analysis of all available such trials combined, however, shows that any intervention (bisphosphonate, vitamin D sterol, or calcitonin) for bone disease in kidney transplant recipients does reduce the risk of fracture in this population. These agents also provide a significant improvement in bone mineral density when given after transplantation, although the clinical significance of this is uncertain due to the lack of validation in bone densitometry in chronic kidney disease. Bisphosphonates have greater efficacy to preserve bone mineral density than vitamin D sterols in head-to-head trials.

Authors' conclusions: 

Treatment with a bisphosphonate, vitamin D sterol or calcitonin after kidney transplantation may protect against immunosuppression-induced reductions in bone mineral density and prevent fracture. Adequately powered trials are required to determine whether bisphosphonates are better than vitamin D sterols for fracture prevention in this population. The optimal route, timing, and duration of administration of these interventions remains unknown.

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Background: 

Patients with chronic kidney disease have significant abnormalities of bone remodeling and mineral homeostasis and are at increased risk of fracture. The fracture risk for a kidney transplant recipient is four times that of the general population and higher than for a patient on dialysis. Randomised controlled trials (RCTs) report the use of bisphosphonates, vitamin D sterols, calcitonin, and hormone replacement therapy to treat bone disease following transplantation.

Objectives: 

To evaluate the use of interventions for treating bone disease following kidney transplantation.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library), Cochrane Renal Group's specialised register, MEDLINE, EMBASE, reference lists, and conference proceedings abstracts without language restriction.

Selection criteria: 

RCTs and quasi-RCTs comparing different treatments for kidney transplant recipients of any age were selected. We excluded all other transplant recipients, including kidney-pancreas transplant recipients.

Data collection and analysis: 

Two authors independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous variables and mean difference (MD) for continuous outcomes.

Main results: 

Twenty-four trials (1,299 patients) were included. No individual intervention (bisphosphonates, vitamin D sterol or calcitonin) was associated with a reduction in fracture risk compared with placebo. Combining results for all active interventions against placebo demonstrated any treatment of bone disease was associated with a reduction in the RR of fracture (RR 0.51, 95% CI 0.27 to 0.99). Bisphosphonates (any route), vitamin D sterol, and calcitonin all had a beneficial effect on the bone mineral density at the lumbar spine. Bisphosphonates and vitamin D sterol also had a beneficial effect on the bone mineral density at the femoral neck. Bisphosphonates had greater efficacy for preventing bone mineral density loss when compared head-to-head with vitamin D sterols. Few or no data were available for combined hormone replacement, testosterone, selective oestrogen receptor modulators, fluoride or anabolic steroids. Other outcomes including all-cause mortality and drug-related toxicity were reported infrequently.

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