Hypertrophy of vascularized bone isograft in rats treated with cyclosporine A.
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.
Tsubone
T
T
Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan.
Shigetomi
M
M
Ihara
K
K
Ikeda
K
K
Merida
L
L
Ohno
T
T
Sugiyama
T
T
Kawai
S
S
D000596:Amino Acids / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D016025:Bone Transplantation; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005360:Fibula / Q000098:blood supply / Q000473:pathology / Q000637:transplantation; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D006984:Hypertrophy / Q000000981:diagnostic imaging / Q000473:pathology; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013977:Tibia / Q000098:blood supply / Q000473:pathology / Q000637:transplantation; D014057:Tomography, X-Ray Computed; D014185:Transplantation, Isogeneic / Q000473:pathology
D000596:Amino Acids; D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C036020:deoxypyridinoline