Inhibition of Heterotopic Ossification With Radiation Therapy in an Animal Model

Schneider, David J.; Moulton, Mark J.R.; Singapuri, Kishor; Chinchilli, Vernon M.; Deol, Gurvinder S.; Krenitsky, Gabriel; Pellegrini, Vincent D.

doi:10.1097/00003086-199810000-00005

Cited by 39 publications

(31 citation statements)

References 32 publications

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“…However, the model is a realistic model of blast injury endured by service members during combat. Although larger animals (ie, rabbit and sheep models) may be better representatives of human HO formation, previous traumatic models using larger animals have had limited success [14,22,26,27]. This model uses a realistic mechanism of injury and reliably induces heterotopic bone without exogenous growth factors.…”

Section: Discussionmentioning

confidence: 99%

Does Blast Medium Affect Heterotopic Ossification in a Blast-amputation Model?

Yoo

Blevins

Gasbarro

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Heterotopic ossification (HO) develops after nearly 2 .3 of traumatic blast amputations in the contemporary battlefield. This phenomenon has potentially devastating consequences for servicemen and women and its pathophysiology warrants further investigation using a previously developed animal blast model. Questions/purposesWe asked, what is the (1) severity (quantity) and (2) type (location) of HO bone formation after a hindlimb blast amputation with two distinct blast media. We hypothesized that a more ''war-relevant'' blast medium could be a more accurate model and potentially intensify the development of HO. Methods Using a Sprague-Dawley rat model, the pathophysiology of ectopic bone formation in a traumatic hindlimb blast amputation was evaluated. Twenty-four animals underwent blast amputations and closure based on a previously established experimental model. Half the amputations were subjected to blasted sand and the other 1/2 to blasted water. Serial orthogonal radiography was performed on each animal until euthanasia at 24 weeks to track the development of HO. Heterotopic bone severity and type were assessed by three independent graders at each time using a novel grading scale to assess quantity and quality of HO. Results All animals had radiographic evidence of HO develop. No differences were observed in ectopic bone development between sand and water blasting regarding severity or type at any time. Animals that received water and sand blasting had moderate HO develop at 24 weeks (median, 2.0 and 2.5 weeks, respectively; range, 1-3 weeks; difference of medians, 0.5; p = 0.67). At the time of euthanasia, 10 animals that were water blasted had Type 3 HO compared with 11 in the sand-blasted group (p = 1.00).The institution of one or more of the authors (DEJ, VDP) has received, during the study period, funding from the United States Department of Defense Congressionally Directed Medical Research Program (Washington, DC, USA). 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 100,000-USD 1,000,000, from the United States Department of Defense Congressionally Directed Medical Research Program (Washington, DC, USA), an amount of USD 100,000-USD 1,000,000 from DePuy Orthopaedics (Warsaw, IN, USA), and USD 100,000-USD 1,000,000 from the Agency for Healthcare Research and Quality (Rockville, MD, USA). Conclusions Our study showed a clear development of HO after hindlimb blast amputation in a Sprague-Dawley rat model; however, no difference was observed in HO development based on the type of blast media. This suggests it is the blast mechanism that induces ectopic bone development, regardless of the blasted medium. The grading scale we developed for our animal-model study provided a reliable means of assessing HO severity and type. Clinical Relevance We anticipate that future investigations will elucidate similarities between service members' wartime extremity injuries and the animal...

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Section: Discussionmentioning

confidence: 99%

Does Blast Medium Affect Heterotopic Ossification in a Blast-amputation Model?

Yoo

Blevins

Gasbarro

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…Thirty 3-kg male New Zealand White rabbits underwent bilateral induction procedures that included femoral reaming with controlled periosteal disruption and intentional gluteal myonecrosis, performed per protocol [39]. No exogenous osteogenic agents were added to the wound.…”

Section: Methodsmentioning

confidence: 99%

“…We previously described an animal model that mimics the human condition of ectopic bone formation after THA by crushing the gluteal muscles and without the use of an exogenous induction agent; the procedure reliably produced HO [39]. However, the progressive cellular process leading to mature HO has been described only in models using exogenous induction agents (eg, BMP or bone matrix).…”

Section: Introductionmentioning

confidence: 99%

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

Tannous¹,

Stall²,

Griffith³

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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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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“…Class 4 shows apparent bone ankylosis of the hip. Brooker did not describe a Class 0 in his original manuscript, but subsequent studies using the Brooker classification have defined Class 0 as the absence of radiographic HO [17,18,23].…”

Section: Descriptionmentioning

confidence: 99%

“…These studies have also incorporated CT scans into radiographic evaluation of HO. Furthermore, a modified Brooker classification has been applied to HO in animal models [18] but these applications have not yet been validated. Topics of ongoing research include HO prophylaxis and optimal surgical treatment of HO, and the Brooker classification continues to be an integral component of research in the field [4,15].…”

Section: Limitationsmentioning

confidence: 99%