Description: OTA 2002 - Session 1 Session I - Combined Session (International Society for Fracture Repair) Fri., 10/11/02 Combined Session, Paper #6, 8:53 AM Growth Factor Expression in a New Atrophic Nonunion Model: Implications
for the Treatment of Fractures Anita Reed, DPhil; Clive Joyner, DPhil; Harry Brownlow, FRCS Orth; Hamish Simpson, Prof/FRCS Orth ; Nuffield Department of Orthopaedic
Surgery, University of Oxford, Oxford, United Kingdom Purpose: The presence and distribution of important growth factors
such as TGF-b, FGF, PDGF and BMP 2/4 has not previously been documented
during abnormal bone healing at both early and late time points. Therefore,
the aims of this study were to develop and validate a clinically relevant
small animal atrophic nonunion model and to test the hypothesis that growth
factor expression is diminished in atrophic nonunions. Methods: Twenty-eight adult female Wistar rats underwent application
of a novel circular-frame external fixator to the right tibia. The periosteum
was removed from 14 of the 28 animals and the intramedullary canal was curetted.
Both insults were performed proximally and distally for a distance equivalent
to one diameter of the tibia. A -mm gap was introduced. Animals were sacrificed
at 1, 3, 8, and 16 weeks. Paraffin sections were immunohistochemically stained
for TGF-b, FGF basic, PDGF and BMP 2/4. Results: At 8 and 16 weeks, all animals in which stripping was
performed went on to form an atrophic nonunion. Those in which stripping
was not performed united successfully. The immunohistochemical results were
as follows. At 1 week, positive staining was observed in the hematoma in
both groups and in the new bone matrix of the healing group. At 3 weeks,
staining was similar in the two groups, with most tissues continuing to
express growth factors. At 8 weeks, the periosteum in the healing group
no longer expressed TGF-b and BMP 2/4 as it began to remodel. The nonunion
group continued to express all four growth factors. At 16 weeks, as the
healing group remodeled, staining of growth factors became weaker in all
tissues and cells. The fibrous tissue in the nonunion group appeared to
be more weakly stained than at earlier time points. Conclusion: These results may have relevance for new therapies
that can be aimed at delivering growth factors to treat fracture nonunions.
At 1, 3, and 8 weeks, the nonunion group appeared to stain similarly to
the healing group. At 16 weeks, however, consistent with our hypothesis,
there was less staining of the fibrous tissue in the nonunion gap than at
earlier time points. These results may suggest that, at 16 weeks, the fibrous
tissue within the nonunion gap had reached a steady state. Therefore, this
may be a suitable time for the delivery of growth factors to the nonunion
site.
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