Interaction between active motion and exogenous transforming growth factor Beta during tibial fracture repair.

OBJECTIVE

Evaluate the effects of axial motion and transforming growth factor beta (TGF-beta) on callus formation and fracture healing.DESIGN Prospective experimental design with a 39-day postfracture recovery.

SETTING

Unrestricted cage activity with weight bearing as tolerated.

ANIMALS

Twenty-two skeletally mature, female New Zealand White rabbits.

INTERVENTIONS

Displaced, closed tibial fractures were reduced and stabilized in external fixators on the fourth day following fracture. Half of the fixators were locked for the duration of healing. The other fixators were locked for one week, then unlocked for the remaining four weeks. Half of the fractures in each fixator group received two injections of recombinant human TGF-beta1 (rhTGF-beta1). One injection was administered at the time of reduction, and the second was given 48 hours later.

MAIN OUTCOME MEASUREMENTS

Interfragmentary axial motion was measured during floor activity. Biomechanical properties were measured during a torsion test to failure. Callus area and the distribution of tissues within the callus were determined by computer-aided histomorphometry.

RESULTS

The administration of TGF-beta1 did not alter callus size, mechanical properties, or the distribution of tissues in the callus of fractures that were stabilized in locked external fixators. Recoverable axial motion fixation increased callus size, quantity of mineralized bone bridging the fracture, and maximum torque relative to locked fixation. The injection of TGF-beta1 negated the beneficial effects of axial motion by promoting the formation of a peripheral callus bridged by fibrous tissue rather than mineralized trabecular bone.

CONCLUSIONS

Injection of rhTGF-beta1 during the first postfracture week does not provide a biologic boost that improves fracture healing. Injection of TGF-beta1 may be detrimental to healing under conditions when fracture motion is present. The results suggest that there is a tendency for exposure to TGF-beta1 to inhibit the normal development of peripheral callus in response to axial interfragmentary motion.