Effects of cerivastatin on vascularized allogenic bone transplantation in rats treated with cyclosporine A.
The aim of the present study was to investigate the effects of oral cerivastatin (0.1 mg/kg/day) on vascularized allogenic transplanted bone that is treated with cyclosporine A (CsA) (10 mg/kg/day) and on vascularized isogenic transplanted bone that is not treated with CsA. Allogenic transplantation was performed on 12-week-old male DA rats with the major histocompatibility antigen (MHC) RT1a (as the donor) and age-matched male Lewis rats with MHC RT1l (as the recipient), and isogenic transplantation was performed on 12-week-old male Lewis rats. After transplantations, 20 rats (10 rats in each transplantation) were randomized into four groups to receive the following treatment for 16 weeks: (1) CsA plus cerivastatin vehicle or (2) CsA plus cerivastatin in the allogenic transplanted rats, and (3) CsA vehicle plus cerivastatin vehicle or (4) CsA vehicle plus cerivastatin in the isogenic transplanted rats. Bone biochemical markers, mineral density, and strength were measured at the end of the study period. Serum levels of osteocalcin (OC) and parathyroid hormone (PTH) and urinary deoxypyridinoline (DPD) level were higher in the allogenic transplanted rats than in the isogenic transplanted rats. In the allogenic transplanted rats, the cerivastatin treatment decreased urinary DPD levels, but not serum OC nor PTH levels. Furthermore, the cerivastatin treatment improved bone mineral density of the allogenic transplanted bones and bone strength of the allogenic reconstructed bones. In contrast, no effect of the cerivastatin treatment was observed in the isogenic transplanted rats. These results suggest that the cerivastatin treatment improves CsA-induced high-turnover osteopenia mainly through the inhibition of bone resorption.
Ohno
T
T
Department of Orthopedic Surgery, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Shigetomi
M
M
Ihara
K
K
Ikeda
K
K
Tsubone
T
T
Matsunaga
T
T
Sugiyama
T
T
Kawai
S
S
D000596:Amino Acids / Q000652:urine; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy / Q000517:prevention & control; D016025:Bone Transplantation / Q000009:adverse effects / Q000379:methods; D016572:Cyclosporine / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D004548:Elasticity / Q000187:drug effects; D005360:Fibula / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D010281:Parathyroid Hormone / Q000097:blood; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013314:Stress, Mechanical; D013977:Tibia / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D014184:Transplantation, Homologous; D016474:Weight-Bearing
D000596:Amino Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D010281:Parathyroid Hormone; D011725:Pyridines; D015675:Osteocalcin; D016572:Cyclosporine; C036020:deoxypyridinoline; C086276:cerivastatin