Effects of bisphosphonates on bone loss in the first year after renal transplantation - A meta-analysis of randomized controlled trials
Department of Internal Medicine III, Division of Nephrology, Medical University Vienna, Vienna, Austria. Nephrology Dialysis Transplantation
(Impact Factor: 3.58).
09/2006; 21(8):2275-81. DOI: 10.1093/ndt/gfl104
Bone loss remains a serious problem after kidney transplantation and is most pronounced during the first months after engraftment. Bisphosphonates are frequently used to treat post-transplant osteodystrophy, but data of large randomized controlled trials (RCTs) are missing.
We, therefore, conducted this systematic review of the literature, searching electronic databases, reference lists and abstracts from scientific meetings to identify RCTs in all languages. The primary outcome assessed was the change in bone mineral density (BMD) during the early post-transplantation period. Based on the mean BMD change presented in the identified publications, the authors were asked for the individual BMD results of all randomized patients, determined at lumbar spine and femoral neck before and after bisphosphonate therapy. Data were pooled for summary estimates by using weighted mean differences of absolute change in BMD. An analysis of covariance was performed, adjusted for individual baseline values, treatment arm and individual trial.
Five studies involving 180 participants were included in our meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing post-transplant osteodystrophy. BMD decline at the lumbar spine within 6-12 months after transplantation was significantly reduced by 0.06 g/cm(2) in patients treated with bisphosphonates (95% CI 0.05-0.08 g/cm(2)). At the femoral neck, the loss of BMD was reduced by 0.05 g/cm(2) during this period (95% CI 0.0-0.11 g/cm(2)), reaching just non-statistical significance. This benefit of bone loss prevention could be reached without major side effects.
Bisphosphonates are effective in preventing bone loss in the early post-transplant period.
Available from: PubMed Central
- "Pamidronate significantly reduces the rate of bone reabsorption and turnover and increases BMD. It maintains or improves the structural and material properties of bone and reduces the risk of fractures , . Studies comparing pamidronate with traditional medicines, such as vitamin D and calcium, demonstrated pamidronate's effectiveness in protecting against early post-transplant bone loss , . "
[Show abstract] [Hide abstract] ABSTRACT: Introduction
The overall effect of pamidronate on bone mass density (BMD) in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined.
Materials and Methods
A comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the “Cochrane Handbook for Systematic Reviews of Interventions 5.0.2” were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH) levels. Fixed or random effect models were used as appropriate.
Six randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD) = 24.62 [16.25, 32.99]). There was no difference between the pamidronate treated and control femoral neck BMD (SMD = 3.53 [−1.84, 8.90]). A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD = −3.101 [−5.33, −0.89]; serum calcium: SMD = 2.18 [−0.8, 5.16]; serum iPTH: SMD = 0.06 [−0.19, 0.31]). Heterogeneity was low for serum calcium and iPTH and high for serum creatinine.
This meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the relationship between serum creatinine and pamidronate.
Available from: onlinelibrary.wiley.com
- "Therefore, tools such as meta-analysis can be applied to pool results, providing a more precise estimate of the effect. For this reason, we recently analyzed the results of the available randomized controlled trials, which investigated the efficacy of bisphosphonate therapy in prevention and treatment of post-transplant ROP within the first year after successful engraftment . This time frame was chosen because of the observation that bone loss is the highest in this early post-transplant period with subsequent slowing and in some cases even stabilization of bone density. "
[Show abstract] [Hide abstract] ABSTRACT: Post-transplant renal osteopathy (ROP) remains a serious problem, which contributes to substantial long-term morbidity of the graft recipients. Bone loss is most pronounced during the first months after engraftment; concerning bone density development in long-term transplant recipients, controversial data exist. The clinical impact of ROP is a marked increase in fracture rate following kidney transplantation compared with both general population and patients on dialysis treatment. The following review will focus on post-transplant ROP and discuss its epidemiology, the clinical features, factors contributing to the pathogenesis of this complication, as well as the evaluation, prevention and treatment options available for kidney allograft recipients.
[Show abstract] [Hide abstract] ABSTRACT: New-onset diabetes mellitus in a previously non-diabetic transplant recipient is a serious adverse event that confers significant morbidity and mortality. The most significant consequences of post-transplant diabetes mellitus (PTDM) in solid organ transplant recipients include decreased patient and graft survival, an increased risk of infectious complications, and morbid cardiovascular events. The development of PTDM in the elderly is of particular concern because this group is already at increased risk of progression of cardiovascular disease. Because the elderly, especially those aged >65 years, are the fastest-growing segment of the renal transplant population, attention needs to be given to PTDM risk reduction and post-transplant management. PTDM develops as a consequence of both impaired insulin production and enhanced peripheral insulin resistance. A number of non-modifiable factors such as age, race, family history, hepatitis C, polycystic kidney disease and emerging genetic causes have been identified as risk factors for PTDM. However, a number of modifiable factors can be targets for intervention in high-risk patients, including bodyweight (through dietary restriction and exercise), hypertension, hyperlipidaemia and the effects of certain immunosuppressive agents. The two agents most responsible for PTDM are tacrolimus and corticosteroids, especially when used in combination. Attempts to modify doses and regimens designed to eliminate or avoid these drugs should be considered. Use of HMG-CoA reductase inhibitors ('statins') and ACE inhibitors is particularly helpful in controlling hypertension and hyperlipidaemia in the elderly because these agents confer protection against future adverse cardiovascular events. Bisphosphonates are also advantageous in controlling the progression of osteoporosis and possible increased risk of bone fractures. Future trials in the elderly should focus on such endpoints as PTDM, post-transplant neoplasia, cardiovascular events and bone fracture events in order to identify the safest regimens that provide the optimal control of rejection while limiting the morbidity from these secondary events.
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