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Heterotopic Bone Formation About the Hip Undergoes Endochondral Ossification: A Rabbit Model

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Clinical Orthopaedics and Related Research®

Abstract

Background

Heterotopic ossification (HO) occurs most commonly after trauma and surgery about the hip and may compromise subsequent function. Currently available animal models describing the cellular progression of HO are based on exogenous osteogenic induction agents and may not reflect the processes following trauma.

Questions/purposes

We therefore sought to characterize the histologic progression of heterotopic bone formation in an animal model that recapitulates the human condition without the addition of exogenous osteogenic material.

Methods

We used a rabbit model that included intramedullary instrumentation of the upper femur and ischemic crush injury of the gluteal muscle. Bilateral surgical induction procedures were performed on 30 animals with the intention of inciting the process of HO; no supplemental osteogenic stimulants were used. Three animals were sacrificed at each of 10 predetermined times between 1 day and 26 weeks postoperatively and the progression of tissue maturation was graded histologically using a five-item scale.

Results

Heterotopic bone reliably formed de novo and consistently followed a pathway of endochondral ossification. Chondroid elements were found in juxtaposition with immature woven bone in all sections that contained mature osseous elements.

Conclusions

These results establish that HO occurs in an animal model mimicking the human condition following surgical trauma about the hip; it is predictable in its histologic progression and follows a pathway of endochondral bone formation.

Clinical Relevance

By showing a consistent pathway of endochondral ossification leading to ectopic bone formation, this study provides a basis for understanding the mechanisms by which HO might be mitigated by interventions.

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Acknowledgments

We thank Nishant Merchant MD and Brian Duggan MD for assistance with the study and Senior Editor Dori Kelly MA for assistance with the manuscript.

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Authors and Affiliations

  1. Department of Orthopaedics, University of Maryland School of Medicine, 22 South Green Street, Suite S-11B, Baltimore, MD, USA

    Oliver Tannous MD, Alec C. Stall MD, Cullen Griffith MD, Christopher T. Donaldson MD & Vincent D. Pellegrini Jr MD

  2. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA

    Rudolph J. Castellani Jr MD

Authors
  1. Oliver Tannous MD
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  2. Alec C. Stall MD
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  3. Cullen Griffith MD
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  4. Christopher T. Donaldson MD
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  5. Rudolph J. Castellani Jr MD
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  6. Vincent D. Pellegrini Jr MD
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Corresponding author

Correspondence to Vincent D. Pellegrini Jr MD.

Additional information

The institution of one or more of the authors (VDP) has received, during the study period, funding from The Hip Society, The United States Department of Defense, Agency for Healthcare Research and Quality, and Orthopaedic Trauma Association. One of the authors certifies that he (VDP) or a member of his immediate family has or may receive payments or benefits, during the study period, an amount of USD 100,001–USD 1,000,000 from DePuy Orthopaedics, Inc (Warsaw, IN).

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.

Clinical Orthopaedics and Related Research neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use.

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.

This work was performed at the Departments of Orthopaedics and Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.

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Tannous, O., Stall, A.C., Griffith, C. et al. Heterotopic Bone Formation About the Hip Undergoes Endochondral Ossification: A Rabbit Model. Clin Orthop Relat Res 471, 1584–1592 (2013). https://doi.org/10.1007/s11999-013-2801-5

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  • DOI: https://doi.org/10.1007/s11999-013-2801-5

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