, Volume 470, Issue 9, pp 2478-2487
Date: 24 Apr 2012

Quantifying Massive Allograft Healing of the Canine Femur In Vivo and Ex Vivo: A Pilot Study

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Abstract

Background

Allograft integration in segmental osseous defects is unpredictable. Imaging techniques have not been applied to investigate angiogenesis and bone formation during allograft healing in a large-animal model.

Questions/purposes

We used dynamic contrast-enhanced (DCE)-MRI and cone beam (CB)-CT to quantify vascularity and bone volume in a canine femoral allograft model and determined their relationship with biomechanical testing and histomorphometry.

Methods

Femoral ostectomy was performed in three dogs and reconstructed with a 5-cm allograft and compression plate. At 0.5, 3, and 6 months, we performed DCE-MRI to quantify vascular permeability (Ktrans) and perfused fraction and CB-CT to quantify bone volume. We also performed posteuthanasia torsional testing and dynamic histomorphometry of the grafted and nonoperated femurs.

Results

DCE-MRI confirmed the avascular nature of allograft healing (perfused fraction, 2.08%–3.25%). CB-CT demonstrated new bone formation at 3 months (26.2, 3.7, and 2.2 cm3) at the graft-host junctions, which remodeled down at 6 months (14.0, 2.2, and 2.0 cm3). The increased bone volume in one subject was confirmed with elevated Ktrans (0.22) at 3 months. CB-CT-identified remodeled bone at 6 months was corroborated by histomorphometry. Allografted femurs recovered only 40% of their strength at 6 months.

Conclusions

CB-CT and DCE-MRI can discriminate differences in angiogenesis and bone formation in the canine allograft model, which has potential to detect a small (32%) drug or device effect on biomechanical healing with only five animals per group.

Clinical Relevance

These radiographic tools may have the potential to assess adjuvant effects on vascular invasion and new bone formation after segmental allograft transplantation.

One or more of the authors (BGS, NE, EMS) have received funding from the Musculoskeletal Transplant Foundation (Edison, NJ, USA). One or more of the authors have received funding from the following grants: NIH PHS AR054041 (EMS), AR056696 (EMS), DE019902 (EMS), AR061307 (EMS), and 1R01EB012048-01A1 (BGS).
All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.
Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.
All in vivo work and ex vivo cone beam CT and imaging analyses were performed at the University of Rochester, Rochester, NY, USA. The ex vivo biomechanics, histology, and histomorphometry were performed at Colorado State University, Fort Collins, CO, USA.