Effect of FK‐506 (tacrolimus) therapy on bone healing of titanium implants: a histometric and biomechanical study in mice

Immunosuppressive agents have been recognized as a factor affecting bone metabolism. The aim of the present study was to evaluate the influence of FK‐506 administration on the healing of bone around titanium implants. Thirty‐two male mice were randomly allocated to two groups: the FK‐506 group (n = 16 mice), which received subcutaneous administration of FK‐506 (1 mg kg^?1 d^?1); and the control group (n = 16 mice), which received saline solution by the same route of administration. After 2 wk, one titanium implant with sandblasted/acid‐etched surface was placed in the femur. The therapy continued until the mice were killed 2 and 4 wk after surgery. The femurs with implants were evaluated by biomechanical testing and histologic analysis. The bone–implant contact (BIC) and bone volume (BV/TV) within a 100‐μm‐wide circumferential zone lateral to the implant surface were histomorphometrically analyzed. Compared with the control group, the FK‐506 group showed significantly lower BIC and BV/TV at both 2 and 4 wk. Biomechanical tests showed that FK‐506 significantly impaired the strength of bone–implant integration at both 2 and 4 wk postoperatively. Our data indicate that immunosuppressive therapy with FK‐506 negatively affects the fixation of titanium implants.