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Characterization of a rat osteotomy model with impaired healing.

Kratzel C, Bergmann C, Duda G, Greiner S, Schmidmaier G, Wildemann B - BMC Musculoskelet Disord (2008)

Bottom Line: The healing progress of the osteotomy model was compared to a previously described closed fracture model.The dimensions of whole reactive callus and the amounts of vessels in defined regions of the callus differed significantly between osteotomized and fractured animals at 10 d post surgery.Moreover, the osteotomy technique is associated with cellular and vascular signs of persistent inflammation within the first 10 d after bone defect and may be a contributory factor to impaired healing.

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Affiliation: Julius Wolff Institut, BCRT, CMSC Charité-Universitätsmedizin Berlin Augustenburger Platz 1, 13353 Berlin, Germany. chris.kratzel@web.de

ABSTRACT

Background: Delayed union or nonunion are frequent and feared complications in fracture treatment. Animal models of impaired bone healing are rare. Moreover, specific descriptions are limited although understanding of the biological course of pathogenesis of fracture nonunion is essential for therapeutic approaches.

Methods: A rat tibial osteotomy model with subsequent intramedullary stabilization was performed. The healing progress of the osteotomy model was compared to a previously described closed fracture model. Histological analyses, biomechanical testing and radiological screening were undertaken during the observation period of 84 days (d) to verify the status of the healing process. In this context, particular attention was paid to a comparison of bone slices by histological and immunohistological (IHC) methods at early points in time, i.e. at 5 and 10 d post bone defect.

Results: In contrast to the closed fracture technique osteotomy led to delayed union or nonunion until 84 d post intervention. The dimensions of whole reactive callus and the amounts of vessels in defined regions of the callus differed significantly between osteotomized and fractured animals at 10 d post surgery. A lower fraction of newly formed bone and cartilaginous tissue was obvious during this period in osteotomized animals and more inflammatory cells were observed in the callus. Newly formed bone tissue accumulated slowly on the anterior tibial side with both techniques. New formation of reparative cartilage was obviously inhibited on the anterior side, the surgical approach side, in osteotomized animals only.

Conclusion: Tibial osteotomy with intramedullary stabilisation in rats leads to pronounced delayed union and nonunion until 84 d post intervention. The early onset of this delay can already be detected histologically within 10 d post surgery. Moreover, the osteotomy technique is associated with cellular and vascular signs of persistent inflammation within the first 10 d after bone defect and may be a contributory factor to impaired healing. The model would be excellent to test agents to promote fracture healing.

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(a and b). Safranin O/von Kossa staining to detect mineralized bone (black staining) of comparable areas in representative tibiae 84 d after osteotomy (a) and fracture (b) and intramedullary stabilization demonstrating nonunion and regular healing respectively. Cavities correspond to the 1 mm wire diameter. Asterisks indicate the proximal and anterior tibial side.
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Figure 2: (a and b). Safranin O/von Kossa staining to detect mineralized bone (black staining) of comparable areas in representative tibiae 84 d after osteotomy (a) and fracture (b) and intramedullary stabilization demonstrating nonunion and regular healing respectively. Cavities correspond to the 1 mm wire diameter. Asterisks indicate the proximal and anterior tibial side.

Mentions: Histological screening at 28, 42 and 84d post surgery revealed microscopically a nonunion of osteotomized tibiae (Fig. 2a) except in 3 out of 6 examined animals at 84 d. These bone samples revealed incomplete union whereby only the periosteal callus was bridged. Histological slices of fractured tibiae [24] revealed bony bridging and status of remodelling until 84 d (Fig. 2b).


Characterization of a rat osteotomy model with impaired healing.

Kratzel C, Bergmann C, Duda G, Greiner S, Schmidmaier G, Wildemann B - BMC Musculoskelet Disord (2008)

(a and b). Safranin O/von Kossa staining to detect mineralized bone (black staining) of comparable areas in representative tibiae 84 d after osteotomy (a) and fracture (b) and intramedullary stabilization demonstrating nonunion and regular healing respectively. Cavities correspond to the 1 mm wire diameter. Asterisks indicate the proximal and anterior tibial side.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2571093&req=5

Figure 2: (a and b). Safranin O/von Kossa staining to detect mineralized bone (black staining) of comparable areas in representative tibiae 84 d after osteotomy (a) and fracture (b) and intramedullary stabilization demonstrating nonunion and regular healing respectively. Cavities correspond to the 1 mm wire diameter. Asterisks indicate the proximal and anterior tibial side.
Mentions: Histological screening at 28, 42 and 84d post surgery revealed microscopically a nonunion of osteotomized tibiae (Fig. 2a) except in 3 out of 6 examined animals at 84 d. These bone samples revealed incomplete union whereby only the periosteal callus was bridged. Histological slices of fractured tibiae [24] revealed bony bridging and status of remodelling until 84 d (Fig. 2b).

Bottom Line: The healing progress of the osteotomy model was compared to a previously described closed fracture model.The dimensions of whole reactive callus and the amounts of vessels in defined regions of the callus differed significantly between osteotomized and fractured animals at 10 d post surgery.Moreover, the osteotomy technique is associated with cellular and vascular signs of persistent inflammation within the first 10 d after bone defect and may be a contributory factor to impaired healing.

View Article: PubMed Central - HTML - PubMed

Affiliation: Julius Wolff Institut, BCRT, CMSC Charité-Universitätsmedizin Berlin Augustenburger Platz 1, 13353 Berlin, Germany. chris.kratzel@web.de

ABSTRACT

Background: Delayed union or nonunion are frequent and feared complications in fracture treatment. Animal models of impaired bone healing are rare. Moreover, specific descriptions are limited although understanding of the biological course of pathogenesis of fracture nonunion is essential for therapeutic approaches.

Methods: A rat tibial osteotomy model with subsequent intramedullary stabilization was performed. The healing progress of the osteotomy model was compared to a previously described closed fracture model. Histological analyses, biomechanical testing and radiological screening were undertaken during the observation period of 84 days (d) to verify the status of the healing process. In this context, particular attention was paid to a comparison of bone slices by histological and immunohistological (IHC) methods at early points in time, i.e. at 5 and 10 d post bone defect.

Results: In contrast to the closed fracture technique osteotomy led to delayed union or nonunion until 84 d post intervention. The dimensions of whole reactive callus and the amounts of vessels in defined regions of the callus differed significantly between osteotomized and fractured animals at 10 d post surgery. A lower fraction of newly formed bone and cartilaginous tissue was obvious during this period in osteotomized animals and more inflammatory cells were observed in the callus. Newly formed bone tissue accumulated slowly on the anterior tibial side with both techniques. New formation of reparative cartilage was obviously inhibited on the anterior side, the surgical approach side, in osteotomized animals only.

Conclusion: Tibial osteotomy with intramedullary stabilisation in rats leads to pronounced delayed union and nonunion until 84 d post intervention. The early onset of this delay can already be detected histologically within 10 d post surgery. Moreover, the osteotomy technique is associated with cellular and vascular signs of persistent inflammation within the first 10 d after bone defect and may be a contributory factor to impaired healing. The model would be excellent to test agents to promote fracture healing.

Show MeSH
Related in: MedlinePlus