Clinical efficacy and safety of pamidronate therapy on bone mass density in early post-renal transplant period: a meta-analysis of randomized controlled trials

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.

Results: 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.

Conclusions: 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.

Figure 1. Flow diagram.

Flow chart of trial selection.

Figure 2. Forest plot of lumbar spine and femoral neck BMD change.

(A). The administration of pamidronate was associated with significant benefit to the intervention group, compared to the control group. (SMD  = 24.62 [16.25, 32.99], p for effect <0.001, p for heterogeneity <0.001, I² = 98.4%). Five studies with 188 patients were analyzed. (B). No significant difference was found in the BMD of the intervention and control groups (SMD  = 3.53 [−1.84, 8.90], p for effect  = 0.198, p for heterogeneity <0.001, I² = 97.6%). Four studies with 129 patients were analyzed. BMD: bone mineral density; SMD: standardized mean difference.

Figure 3. Forest plot of the change in serum creatinine, calcium and iPTH.

(A). There was a significant increase in the serum creatinine of the intervention group (SMD  = −3.101 [−5.33, −0.89], p for effect  = 0.006, p for heterogeneity <0.001, I² = 97.1%). Four studies with 221 patients were analyzed.(B). No significant difference was detected in the serum calcium of the intervention and control groups (serum calcium: SMD  = 2.18 [−0.8, 5.16], p for effect  = 0.151, p for heterogeneity <0.001, I² = 98.3%). Five studies with 246 patients were analyzed. (C). There was no difference in the serum iPTH of the intervention and control groups at 1-year follow-up (SMD  = 0.06 [−0.19, 0.31], p for effect  = 0.646, p for heterogeneity  = 0.836, I² = 0.00%). Five studies with 246 patients were analyzed. iPTH: intact parathyroid hormone. SMD: standardized mean difference.