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Hypertrophy of Vascularized Bone Isograft in Rats Treated with Cyclosporine A

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Abstract

The aim of this study was to investigate the effects of cyclosporine A (CsA) on vascularized tibio-fibula isograft between 12-week-old male Lewis rats. After transplantation, 45 rats were randomly allocated to one of the following 7 treatment groups: (1) 4-week vehicle (n = 5), (2) 4-week CsA (n = 5), (3) 8-week vehicle (n = 10), (4) 8-week CsA (n = 10), (5) 4-week CsA followed by 4-week vehicle (n = 5), (6) 16-week vehicle (n = 5), or (7) 4-week CsA followed by 12-week vehicle (n = 5). In soft X-ray and micro-computed tomography examination, hypertrophic change of the grafted bones was apparent in the 4- and 8-week CsA groups. Mineral apposition rate and bone formation rate of the grafted bones in the 4-week CsA group were markedly higher than those in the 4-week vehicle group. In the 4- and 8-week CsA groups, however, bone mineral density (BMD) of the grafted bones was lower and strength of the reconstructed bones was weaker than the 4- and 8-week vehicle groups. Urinary deoxypyridinoline (DPD) level was higher in the 4- and 8-week CsA groups than in the 4- and 8-week vehicle groups. The group of 4-week CsA followed by 4-week vehicle had a level of urinary DPD equal to the 8-week vehicle group, but their BMD of the grafted bones was lower and strength of the reconstructed bones was weaker than the 8-week vehicle group. By contrast, the group of 4-week CsA followed by 12-week vehicle had BMD of the grafted bones and strength of the reconstructed bones similar to the 16-week vehicle group. These findings demonstrate that short-term CsA treatment induces hypertrophic change of vascularized bone graft with high-turnover bone loss, and strength of the reconstructed bone is gradually restored after the cessation of CsA treatment.

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Acknowledgements

This study was supported in part by a grant-in-aid for Scientific Research from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan

    T. Tsubone, M. Shigetomi, K. Ihara, K. Ikeda, L. Merida, T. Ohno, T. Sugiyama & S. Kawai

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  1. T. Tsubone
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  2. M. Shigetomi
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  3. K. Ihara
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  4. K. Ikeda
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  5. L. Merida
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  6. T. Ohno
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  7. T. Sugiyama
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  8. S. Kawai
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Correspondence to M. Shigetomi.

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Tsubone, T., Shigetomi, M., Ihara, K. et al. Hypertrophy of Vascularized Bone Isograft in Rats Treated with Cyclosporine A . Calcif Tissue Int 73, 393–399 (2003). https://doi.org/10.1007/s00223-002-2147-6

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  • DOI: https://doi.org/10.1007/s00223-002-2147-6

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