title: Immunosuppression with FK506 has no influence on fracture healing in the rat.
abstract: Immunosuppressant drugs like cyclosporine A and FK506 are widely used for solid organ transplantation. They are accelerating bone remodeling but cause net bone loss. The aim of this study was to investigate the effect of FK506 on fracture healing in the rat. Eighty Lewis rats were divided into four groups, which received FK506 (1 mg/kg BW) or no treatment for 2 or 4 weeks, beginning after production of a closed, nondisplaced unilateral tibial fracture. Radiographic, histological, and biomechanical studies were used to evaluate fracture healing and histomorphometric analysis of the tibial metaphysis of the intact contralateral side was performed. Radiographs revealed no difference of the healing of the control fractures compared with the fractures in the FK506-treated group at 2 and 4 weeks. The mechanical parameters of the tested contralateral intact tibiae and of the fracture callus demonstrated no difference between control and immunosuppressed animals. Tibial bone histomorphometry revealed increased measures of bone formation and bone resorption, accompanied by a significant reduction of percent trabecular area. At 4 weeks, the fractures showed osseous healing with woven bone at the fracture site and only minimal amounts of cartilage. Histological grading was not different between the control and the FK506 group at both time points. We conclude that systemic application of FK506 has no biomechanical and histological effects of experimental fracture healing in the rat. However, resorption far in excess of formation leads to a net bone loss in the trabecular bone of the tibia that has no effect on the stability of the intact bone.
authors.affiliation: Department of Trauma Surgery and Laboratory for Experimental Orthopaedics, University Hospital Mannheim, Ruprecht-Karls-University of Heidelberg, D-68165 Mannheim, Germany. gregor.voggenreiter@uch.ma.uni-heidelberg.de
authors.forename: Gregor
authors.initials: G
authors.lastname: Voggenreiter
authors.forename: Patrizia
authors.initials: P
authors.lastname: Siozos
authors.forename: Eva
authors.initials: E
authors.lastname: Hunkemöller
authors.forename: Stefan
authors.initials: S
authors.lastname: Heute
authors.forename: Markus
authors.initials: M
authors.lastname: Schwarz
authors.forename: Udo
authors.initials: U
authors.lastname: Obertacke
mesh_terms: D000818:Animals; D017102:Fracture Healing / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000627:therapeutic use*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D013978:Tibial Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus