Effects of short-term cyclosporin-A on biomechanical properties of intact and fractured bone in the rat.

ABSTRACT

Cyclosporin-A is a new immunosuppressant drug being used widely for solid organ transplantation. The systemic effects of Cyclosporin-A on the skeletal system have not previously been defined. This study examined the effects of Cyclosporin-A on biomechanical properties of intact bone and fracture repair in a rat model. Closed midshaft femoral fractures were produced over a preplaced intramedullary pin. Cyclosporin-A, dissolved in olive oil and administered by gavage, was begun the day following surgery and continued for 14 consecutive days at a dose known to prolong solid organ allograft survival in rats (7 mg/kg/day), and a second group of control animals received comparable volumes of plain olive oil under identical circumstances. Groups of both experimental and control animals were killed at 4, 8, 12, or 16 weeks following fracture, after which both intact and fractured femurs were tested to failure in torsion. As judged by torque, angular deformation, stiffness, and energy absorption, Cyclosporin-A did not significantly alter the biomechanical properties of fracture repair or intact bone turnover. Based on current biomechanical data, we can find no reason to discourage the short-term clinical use of Cyclosporin-A in patients with or without fractures. Histomorphometric studies are required to accurately assess the biologic effects of this drug on bone biology and to complete the analysis of skeletal toxicity.