Teruyasu Ohno

Skeletal reconstruction by vascularized allogenic bone transplantation: effects of statin in rats.

Background. Some statins have been reported to suppress the immune system and increase the expression of bone morphogenetic protein-2 gene that plays a pivotal role in bone regeneration. Methods. The effects of cerivastatin on skeletal reconstruction by vascularized bone allograft were investigated in a rat tibia-fibula graft model. After transplantation, the recipient rats were treated with vehicle, low-dose cerivastatin, high-dose cerivastatin, or cyclosporine A. Results. Transplanted bones treated with low-dose cerivastatin and vehicle failed to unite with the recipient bones. In contrast, high-dose cerivastatin induced the bone union as effectively as cyclosporine A. Histologically, high-dose cerivastatin-treated transplanted bones were nonvital, but new bone formation occurred at the outer layer of the nonvital cortex. Conclusion. These results indicate that statins could promote fracture healing. Because transplant recipients have the increased risks of osteoporotic fracture and hypercholesterolemia, statins may be a good choice in the treatment of these patients.

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.

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.

Role of vascularised tissue transfer after oncological resection in the upper extremity

We reviewed 12 patients who had had vascularised tissue transfer after oncological resection in the upper extremity. All patients had immediate reconstruction, and one had a double tissue transfer. Tissues used were skin flaps, free muscles, and vascularised fibulas, for resurfacing the wound, motor recovery, and reconstruction of large bony defects, respectively. All the patients returned early to their daily activities. Although local recurrences were encountered in two patients, they were again rendered disease‐free by salvage operations. Two patients had secondary reconstructions using pedicle latissimus dorsi flaps for late problems, including one of the two patients who developed a local recurrence. The mean functional score using the system devised by the Musculoskeletal Tumor Society was 84%. All the upper extremities were successfully rescued with satisfactory function. Vascularised tissue transfer was invaluable for achieving both curative resection of the tumour and a useful upper extremity.