Session III - Polytrauma Fracture Healing

·*Recombinant Growth Hormone Accelerates the Healing of Segmental Bone Defects: An Animal Study in Minipigs

Stefan Kolbeck, MD; Hermann Bail, MD; Kirsten Raun, PhD; (e-NOVO Nordisk A/S Copenhagen, Denmark) Gerhard Schmidmaier, MD; Norbert P. Haas, MD; Michael Raschke, MD, Department of Trauma & Reconstructive Surgery, Charité, Humboldt-University, Berlin, Germany

Purpose: Treatment of segmental bone loss in long bones is one of the most challenging problems in orthopaedic surgery. Procedures such as bone grafting or bone transport implicate a considerable donor side morbidity and require a long treatment period.

A previous animal study clearly demonstrated acceleration of regenerate consolidation in distraction osteogenesis by application of recombinant growth hormone. Up to now the effect of r-pGH on secondary fracture healing in a large animal model with a segmental bone defect remains unclear. To address this problem we asked the following research question: Does systemic administration of recombinant growth hormone accelerate bone formation in a defect model with secondary fracture healing?

Methods: 24 mature Yucatan micropigs were ranked according to their age and weight and equally distributed into two treatment groups. The animals in the study group received a daily subcutaneous injection of r-pGH (100 µg/kg bodyweight) starting the day of surgery, while the animals in the control group received sodium-chloride as a placebo. A standardized 1cm defect in the mid-shaft area of the right tibia was created with an oscillating saw, the periosteum was incised longitudinally and sutured after stabilizing the osseous defect with plate fixation. The animals were sacrificed 6 weeks post surgery. After plate removal high resolution computertomography of the defect zone was performed. Using a standardized hydroxyl-apatite phantom the bone mineral density (BMD) and the bone mineral content (BMC) of the defect zone was calculated. After CT-analysis the tibiae were embedded and torsional stiffness and torsional failure load were determined in a material testing machine. For statistical analysis of both groups, the Mann Whitney U test was used.

Results: The tibiae of the r-pGH- treated group exhibited 70% higher torsional failure load than the tibiae of the placebo group (GH: 18.06 ± 5.91 Nm; placebo: 10.62 ± 5.2 Nm; p < 0.05). Compared to the intact contralateral tibia, torsional stiffness and torsional failure load values of the GH-group were significant higher than in the placebo group (torsional stiffness: GH: 135 ± 68%, placebo: 65 ± 30%, p = 0.005; torsional failure load: GH: 75 ± 30%, pacebo: 41 ± 22%, p = 0.006) (Fig.1).

Figure 1: Torsional stiffness and maximum torsional moment in % of the contralateral tibia: GH-treated vs. placebo group.

The CT-measurements revealed a significant difference for the BMC data of the defect zone between the GH-group and the placebo-group (GH: BMC=2833 ± 679 mg; placebo: BMC=2215 ± 636 mg; p < 0.05) (Fig.2).

Figure 2: Bone Mineral Content of the defect in the GH-treated and placebo group.

The BMD in the defect zone was similar in both groups (GH: BMD=668 ± 60 mg/ml; placebo: BMD=629 ± 52 mg/ml; p = 0.12) (Fig.3).

Figure 3: Bone Mineral density of the defect in the GH-treated and placebo group

Discussion: The biomechanical data demonstrate that the administration of r-pGH increases both the torsional stiffness as well as the torsional failure load in this model. These results confirm previous investigations where in distraction osteogenesis systemic administration of growth hormone resulted in an accelerated regenerate consolidation.

The quantitative CT measurements of the callus in the defect zone demonstrated that a larger amount of mineralized tissue could be observed in the GH treated group. The BMD values for both groups were very similar, indicating that the structure of the callus tissue in both groups is comparable.

Conclusion: Our results strongly suggest that systemic administration of homologous growth hormone accelerates new bone formation in secondary fracture healing. This could be a future clinical tool for cases of segmental bone loss to prevent delayed union or pseudarthrosis.