ABSTRACT: 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.
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.
After skeletal reconstruction by vascularized tibial grafting, adult recipient rats were treated with intramuscular CsA (10 mg/kg/day) and low-dose (0.2 microg/kg/week) or high-dose (2 microg/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.
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.
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.
Osteoporosis International 12/2007; 18(11):1531-40. · 4.58 Impact Factor
ABSTRACT: We used a new internal fixative implant, the AO clavicle hook-plate, for treatment of unstable fractures of the distal clavicle. This study describes the operative procedure and the clinical results obtained, as well as discussion of the advantages and problems encountered.
Fifteen consecutive patients with unstable fractures of the distal clavicle (Neer type II) were treated using AO clavicle hook-plates. The average age of patients was 47 years and there were 13 males and 2 females. The mean follow-up period was 15.5 months. Plain radiographs of clavicles were used to assess bony union. Functional recovery of the shoulder joint was assessed using the Constant-Murley scoring system.
All fractures eventually achieved solid bony union within 4 months after surgery. Thirteen patients (87%) showed hook migration into the acromion. Clinical results were excellent with a mean Constant-Murley score of 89 points at final follow-up.
AO clavicle hook-plates are useful fixative implants for unstable fractures of the distal clavicle. Static fixation was achieved and physiotherapy can be started immediately after surgery. Early removal of the implant is recommended however because hooks inserted under the acromion migrated into the bone in most cases.
Archives of Orthopaedic and Trauma Surgery 05/2007; 127(3):191-4. · 1.37 Impact Factor
ABSTRACT: 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.
Calcified Tissue International 02/2003; 72(1):50-6. · 2.38 Impact Factor