Interventions for preventing bone disease in kidney transplant recipients.
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.


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


METHODS
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. Date of last search: May 2006


METHODS
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.


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


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.


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.
Palmer
S C
SC
University of Otago, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand. suetoniapalmer@clear.net.nz
McGregor
D O
DO
Strippoli
G F
GF
D015519:Bone Density / Q000187:drug effects; D001847:Bone Diseases / Q000209:etiology / Q000517:prevention & control; D002116:Calcitonin / Q000627:therapeutic use; D002118:Calcium / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000627:therapeutic use
D004164:Diphosphonates; D014807:Vitamin D; D002116:Calcitonin; D002118:Calcium