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Osteoporosis International

Published in:

01-11-2007 | Original Article

Effects of bisphosphonate treatment on bone repair under immunosuppression using cyclosporine A in adult rats

Authors: T. Matsunaga, M. Shigetomi, T. Hashimoto, H. Suzuki, T. Gondo, H. Tanaka, T. Sugiyama, T. Taguchi

Published in: Osteoporosis International | Issue 11/2007

Abstract

Summary

The effect of cyclosporine A on bone turnover remains unclear. Using adult rats with vascularized bone transplantation, we show that long-term cyclosporine A administration increases bone turnover and zoledronic acid treatment enhances the reconstruction of cyclosporine A-administered skeleton. Bisphosphonates might be efficacious in human bone repair under immunosuppression using cyclosporine A.

Introduction

Bisphosphonate treatment effectively prevents bone loss after transplantation. However, recent evidence from gain- and loss-of-function experiments has indicated that calcineurin inhibitors, such as cyclosporine A (CsA), reduce bone turnover, and severely suppressed bone turnover might delay the union of human fractured bone. The purpose of this study was to investigate the effects of bisphosphonate treatment on the repair of CsA-administered skeleton.

Methods

After skeletal reconstruction by vascularized tibial grafting, adult recipient rats were treated with intramuscular CsA (10 mg/kg/day) and low-dose (0.2 μg/kg/week) or high-dose (2 μg/kg/week) subcutaneous zoledronic acid alone or in combination for 8 weeks. Biochemical parameters were measured in blood and urine. The reconstructed skeleton was analyzed using soft X-ray, histology, dual energy X-ray absorptiometry, and three-point bending test.

Results

CsA induced mild renal dysfunction, hyperparathyroidism and high bone turnover. High-dose zoledronic acid delayed cortical bone union at the distal host-graft junction, but its combination with CsA did not cause such a delay. High-dose zoledronic acid prevented CsA-induced bone loss and bone fragility in the reconstructed skeleton.

Conclusion

In this rat model, long-term CsA administration increases bone turnover, at least partly, through hyperparathyroidism and high-dose zoledronic acid treatment does not impair the union of CsA-administered bone.

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Title: Effects of bisphosphonate treatment on bone repair under immunosuppression using cyclosporine A in adult rats
Authors: T. Matsunaga
M. Shigetomi
T. Hashimoto
H. Suzuki
T. Gondo
H. Tanaka
T. Sugiyama
T. Taguchi
Publication date: 01-11-2007
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 11/2007
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-007-0387-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of bisphosphonate treatment on bone repair under immunosuppression using cyclosporine A in adult rats

Abstract

Summary

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

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