Skip to main content
Top
Published in: Clinical Orthopaedics and Related Research® 8/2015

01-08-2015 | Basic Research

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

Authors: David E. Jaffe, MD, David Yoo, MS, Jason Blevins, BA, Gregory Gasbarro, MS, Tyler Hughes, BA, Ebrahim Paryavi, MD, MPH, Thao Nguyen, MD, William L. Fourney, PhD, Vincent D. Pellegrini Jr, MD

Published in: Clinical Orthopaedics and Related Research® | Issue 8/2015

Login to get access

Abstract

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/purposes

We 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).

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 model used in our study, and with focused future research this model may have beneficial therapeutic implications as the pathophysiology of HO development is further understood.
Literature
1.
go back to reference Baldwin K, Hosalkar HS, Donegan DJ, Rendon N, Ramsey M, Keenan MA. Surgical resection of heterotopic bone about the elbow: an institutional experience with traumatic and neurologic etiologies. J Hand Surg Am. 2011;36:798–803.PubMedCrossRef Baldwin K, Hosalkar HS, Donegan DJ, Rendon N, Ramsey M, Keenan MA. Surgical resection of heterotopic bone about the elbow: an institutional experience with traumatic and neurologic etiologies. J Hand Surg Am. 2011;36:798–803.PubMedCrossRef
2.
go back to reference Billings PC, Fiori JL, Bentwood JL, O’Connell MP, Jiao X, Nussbaum B, Caron RJ, Shore EM, Kaplan FS. Dysregulated BMP signaling and enhanced osteogenic differentiation of connective tissue progenitor cells from patients with fibrodysplasia ossificans progressiva (FOP). J Bone Miner Res. 2008;23:305–313.PubMedCentralPubMedCrossRef Billings PC, Fiori JL, Bentwood JL, O’Connell MP, Jiao X, Nussbaum B, Caron RJ, Shore EM, Kaplan FS. Dysregulated BMP signaling and enhanced osteogenic differentiation of connective tissue progenitor cells from patients with fibrodysplasia ossificans progressiva (FOP). J Bone Miner Res. 2008;23:305–313.PubMedCentralPubMedCrossRef
3.
go back to reference Brooker AF, Bowerman JW, Robinson RA, Riley LH Jr. Ectopic ossification following total hip replacement: incidence and a method of classification. J Bone Joint Surg Am. 1973;55:1629–1632.PubMed Brooker AF, Bowerman JW, Robinson RA, Riley LH Jr. Ectopic ossification following total hip replacement: incidence and a method of classification. J Bone Joint Surg Am. 1973;55:1629–1632.PubMed
4.
go back to reference Cipriano CA, Pill SG, Keenan MA. Heterotopic ossification following traumatic brain injury and spinal cord injury. J Am Acad Orthop Surg. 2009;17:689–697.PubMed Cipriano CA, Pill SG, Keenan MA. Heterotopic ossification following traumatic brain injury and spinal cord injury. J Am Acad Orthop Surg. 2009;17:689–697.PubMed
5.
go back to reference Covey DC. Blast and fragment injuries of the musculoskeletal system. J Bone Joint Surg Am. 2002;84:1221–1234.PubMed Covey DC. Blast and fragment injuries of the musculoskeletal system. J Bone Joint Surg Am. 2002;84:1221–1234.PubMed
6.
go back to reference Covey DC. Combat orthopaedics: a view from the trenches. J Am Acad Orthop Surg. 2006;14(10 spec no):S10–S17. Covey DC. Combat orthopaedics: a view from the trenches. J Am Acad Orthop Surg. 2006;14(10 spec no):S10–S17.
7.
go back to reference Forsberg JA, Pepek JM, Wagner S, Wilson K, Flint J, Andersen RC, Tadaki D, Gage FA, Stojadinovic A, Elster EA. Heterotopic ossification in high-energy wartime extremity injuries: prevalence and risk factors. J Bone Joint Surg Am. 2009;91:1084–1091.PubMedCrossRef Forsberg JA, Pepek JM, Wagner S, Wilson K, Flint J, Andersen RC, Tadaki D, Gage FA, Stojadinovic A, Elster EA. Heterotopic ossification in high-energy wartime extremity injuries: prevalence and risk factors. J Bone Joint Surg Am. 2009;91:1084–1091.PubMedCrossRef
8.
go back to reference Genêt F, Jourdan C, Schnitzler A, Lautridou C, Guillemot D, Judet T, Poiraudeau S, Denormandie P. Troublesome heterotopic ossification after central nervous system damage: a survey of 570 surgeries. PLoS One. 2011;6:e16632.PubMedCentralPubMedCrossRef Genêt F, Jourdan C, Schnitzler A, Lautridou C, Guillemot D, Judet T, Poiraudeau S, Denormandie P. Troublesome heterotopic ossification after central nervous system damage: a survey of 570 surgeries. PLoS One. 2011;6:e16632.PubMedCentralPubMedCrossRef
9.
go back to reference Hofmeister EP, Mazurek M, Ingari J. Injuries sustained to the upper extremity due to modern warfare and the evolution of care. J Hand Surg Am. 2007;32:1141–1147.PubMedCrossRef Hofmeister EP, Mazurek M, Ingari J. Injuries sustained to the upper extremity due to modern warfare and the evolution of care. J Hand Surg Am. 2007;32:1141–1147.PubMedCrossRef
10.
go back to reference Jackson WM, Aragon AB, Bulken-Hoover JD, Nesti LJ, Tuan RS. Putative heterotopic ossification progenitor cells derived from traumatized muscle. J Orthop Res. 2009;27:1645–1651.PubMedCentralPubMedCrossRef Jackson WM, Aragon AB, Bulken-Hoover JD, Nesti LJ, Tuan RS. Putative heterotopic ossification progenitor cells derived from traumatized muscle. J Orthop Res. 2009;27:1645–1651.PubMedCentralPubMedCrossRef
11.
go back to reference Kaplan FS, Glaser DL, Hebela N, Shore EM. Heterotopic ossification. J Am Acad Orthop Surg. 2004;12:116–125.PubMed Kaplan FS, Glaser DL, Hebela N, Shore EM. Heterotopic ossification. J Am Acad Orthop Surg. 2004;12:116–125.PubMed
12.
go back to reference Leiste UH, Fourney WL, Duff T. Experimental studies to investigate pressure loading on target plates. Blasting and Fragmentation Journal. 2013;7:99–126. Leiste UH, Fourney WL, Duff T. Experimental studies to investigate pressure loading on target plates. Blasting and Fragmentation Journal. 2013;7:99–126.
13.
go back to reference Mavrogenis AF, Soucacos PN, Papagelopoulos PJ. Heterotopic ossification revisited. Orthopedics. 2011;34:177.PubMedCrossRef Mavrogenis AF, Soucacos PN, Papagelopoulos PJ. Heterotopic ossification revisited. Orthopedics. 2011;34:177.PubMedCrossRef
14.
go back to reference Michelsson JE, Granroth G, Andersson LC. Myositis ossificans following forcible manipulation of the leg: a rabbit model for the study of heterotopic bone formation. J Bone Joint Surg Am. 1980;62:811–815.PubMed Michelsson JE, Granroth G, Andersson LC. Myositis ossificans following forcible manipulation of the leg: a rabbit model for the study of heterotopic bone formation. J Bone Joint Surg Am. 1980;62:811–815.PubMed
15.
go back to reference Murray CK, Hsu JR, Solomkin JS, Keeling JJ, Andersen RC, Ficke JR, Calhoun JH. Prevention and management of infections associated with combat-related extremity injuries. J Trauma. 2008;64(3 suppl):S239–251.PubMedCrossRef Murray CK, Hsu JR, Solomkin JS, Keeling JJ, Andersen RC, Ficke JR, Calhoun JH. Prevention and management of infections associated with combat-related extremity injuries. J Trauma. 2008;64(3 suppl):S239–251.PubMedCrossRef
16.
go back to reference Owens BD, Kragh JF Jr, Macaitis J, Svoboda SJ, Wenke JC. Characterization of extremity wounds in Operation Iraqi Freedom and Operation Enduring Freedom. J Orthop Trauma. 2007;21:254–257.PubMedCrossRef Owens BD, Kragh JF Jr, Macaitis J, Svoboda SJ, Wenke JC. Characterization of extremity wounds in Operation Iraqi Freedom and Operation Enduring Freedom. J Orthop Trauma. 2007;21:254–257.PubMedCrossRef
17.
go back to reference Pape HC, Marsh S, Morley JR, Krettek C, Giannoudis PV. Current concepts in the development of heterotopic ossification. J Bone Joint Surg Br. 2004;86:783–787.PubMedCrossRef Pape HC, Marsh S, Morley JR, Krettek C, Giannoudis PV. Current concepts in the development of heterotopic ossification. J Bone Joint Surg Br. 2004;86:783–787.PubMedCrossRef
18.
go back to reference Potter BK, Burns TC, Lacap AP, Granville RR, Gajewski DA. Heterotopic ossification in the residual limbs of traumatic and combat-related amputees. J Am Acad Orthop Surg. 2006;14(10 spec no):S191–197. Potter BK, Burns TC, Lacap AP, Granville RR, Gajewski DA. Heterotopic ossification in the residual limbs of traumatic and combat-related amputees. J Am Acad Orthop Surg. 2006;14(10 spec no):S191–197.
19.
go back to reference Potter BK, Burns TC, Lacap AP, Granville RR, Gajewski DA. Heterotopic ossification following traumatic and combat-related amputations: prevalence, risk factors, and preliminary results of excision. J Bone Joint Surg Am. 2007;89:476–486.PubMedCrossRef Potter BK, Burns TC, Lacap AP, Granville RR, Gajewski DA. Heterotopic ossification following traumatic and combat-related amputations: prevalence, risk factors, and preliminary results of excision. J Bone Joint Surg Am. 2007;89:476–486.PubMedCrossRef
20.
go back to reference Rumi MN, Deol GS, Bergandi JA, Singapuri KP, Pellegrini VD Jr. Optimal timing of preoperative radiation for prophylaxis against heterotopic ossification: a rabbit hip model. J Bone Joint Surg Am. 2005;87:366–373.PubMedCrossRef Rumi MN, Deol GS, Bergandi JA, Singapuri KP, Pellegrini VD Jr. Optimal timing of preoperative radiation for prophylaxis against heterotopic ossification: a rabbit hip model. J Bone Joint Surg Am. 2005;87:366–373.PubMedCrossRef
21.
go back to reference Rumi MN, Deol GS, Singapuri KP, Pellegrini VD Jr. The origin of osteoprogenitor cells responsible for heterotopic ossification following hip surgery: an animal model in the rabbit. J Orthop Res. 2005;23:34–40.PubMedCrossRef Rumi MN, Deol GS, Singapuri KP, Pellegrini VD Jr. The origin of osteoprogenitor cells responsible for heterotopic ossification following hip surgery: an animal model in the rabbit. J Orthop Res. 2005;23:34–40.PubMedCrossRef
22.
go back to reference Schneider DJ, Moulton MJ, Singapuri K, Chinchilli V, Deol GS, Krenitsky G, Pellegrini VD Jr. The Frank Stinchfield Award: Inhibition of heterotopic ossification with radiation therapy in an animal model. Clin Orthop Relat Res. 1998;355:35–46.PubMedCrossRef Schneider DJ, Moulton MJ, Singapuri K, Chinchilli V, Deol GS, Krenitsky G, Pellegrini VD Jr. The Frank Stinchfield Award: Inhibition of heterotopic ossification with radiation therapy in an animal model. Clin Orthop Relat Res. 1998;355:35–46.PubMedCrossRef
23.
go back to reference Tannous O, Griffith C, O’Toole RV, Pellegrini VD Jr. Heterotopic ossification after extremity blast amputation in a Sprague-Dawley rat animal model. J Orthop Trauma. 2011;25:506–510.PubMedCrossRef Tannous O, Griffith C, O’Toole RV, Pellegrini VD Jr. Heterotopic ossification after extremity blast amputation in a Sprague-Dawley rat animal model. J Orthop Trauma. 2011;25:506–510.PubMedCrossRef
24.
go back to reference Thomas BJ, Amstutz HC. Results of the administration of diphosphonate for the prevention of heterotopic ossification after total hip arthroplasty. J Bone Joint Surg Am. 1985;67:400–403.PubMed Thomas BJ, Amstutz HC. Results of the administration of diphosphonate for the prevention of heterotopic ossification after total hip arthroplasty. J Bone Joint Surg Am. 1985;67:400–403.PubMed
25.
go back to reference Vasileiadis GI, Sakellariou VI, Kelekis A, Galanos A, Soucacos PN, Papagelopoulos PJ, Babis GC. Prevention of heterotopic ossification in cases of hypertrophic osteoarthritis submitted to total hip arthroplasty: etidronate or indomethacin? J Musculoskelet Neuronal Interact. 2010;10:159–165.PubMed Vasileiadis GI, Sakellariou VI, Kelekis A, Galanos A, Soucacos PN, Papagelopoulos PJ, Babis GC. Prevention of heterotopic ossification in cases of hypertrophic osteoarthritis submitted to total hip arthroplasty: etidronate or indomethacin? J Musculoskelet Neuronal Interact. 2010;10:159–165.PubMed
26.
go back to reference Walton M, Rothwell AG. Reactions of thigh tissues of sheep to blunt trauma. Clin Orthop Relat Res. 1983;176:273–281.PubMed Walton M, Rothwell AG. Reactions of thigh tissues of sheep to blunt trauma. Clin Orthop Relat Res. 1983;176:273–281.PubMed
27.
go back to reference Zaccalini PS, Urist MR. Traumatic periosteal proliferations in rabbits: the enigma of experimental myositis ossificans traumatica. J Trauma. 1964;4:344–357.PubMedCrossRef Zaccalini PS, Urist MR. Traumatic periosteal proliferations in rabbits: the enigma of experimental myositis ossificans traumatica. J Trauma. 1964;4:344–357.PubMedCrossRef
Metadata
Title
Does Blast Medium Affect Heterotopic Ossification in a Blast-amputation Model?
Authors
David E. Jaffe, MD
David Yoo, MS
Jason Blevins, BA
Gregory Gasbarro, MS
Tyler Hughes, BA
Ebrahim Paryavi, MD, MPH
Thao Nguyen, MD
William L. Fourney, PhD
Vincent D. Pellegrini Jr, MD
Publication date
01-08-2015
Publisher
Springer US
Published in
Clinical Orthopaedics and Related Research® / Issue 8/2015
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-015-4320-z

Other articles of this Issue 8/2015

Clinical Orthopaedics and Related Research® 8/2015 Go to the issue

Symposium: Sex Differences in Musculoskeletal Disease and Science

Editorial Comment: Symposium: Sex Differences in Musculoskeletal Disease and Science