Kalça cerrahisi sonrası heterotopik ossifikasyon incelemesi için yeni bir küçük hayvan modeli

Abstract

Amaç: Heterotopik ossifikasyon (HO)–yumuşak dokularda kemik oluşumu–pelvis ve kalça cerrahisi sonrası sık görülen bir sorundur ama temelinde yatan patojenik mekanizmalar hakkında çok az bilinmektedir. Heterotopik ossifikasyona karşı yöneltilen yeni profilaktik tedavi rejimlerini değerlendirmek ve geliştirmek için hayvan modellerinde temelde yatan patojenleri irdelemek önemlidir. Ancak, HO için önceden geliştirilen küçük hayvan modelleri potansiyel olarak HO’ya sebep olan cerrahi ya da travma mekanizmalarını örnek almamıştır. Dolayısıyla, bu çalışmanın amacı eksiksiz bir biçimde HO’ya yol açabilecek bir kalça cerrahisini taklit eden yeni bir küçük hayvan modeli geliştirmekti.

Çalışma planı: Yirmi erkek Wistar sıçan, üç adımda femoral kanal 2 mm’ye kadar delinen ve kas lezyonu oluşturulan bir sağ kalça cerrahisine tabi tutuldu. Operasyondan 12 hafta sonra mikro-bilgisayarlı tomografi kullanılarak heterotopik kemik miktarı değerlendirildi.

Bulgular: Yirmi hayvanın 18’inde, operasyondan 12 hafta sonra kalça çevresinde HO görüldü. Heterotopik kemik miktarı çok küçük parçacıklardan neredeyse ankiloz seviyesine kadar değişkenlik gösterdi.

Çıkarımlar: Ekzojen osteojenik uyarıcı kullanmayan ve eksiksiz bir biçimde HO’ya yol açan kalça/pelvik cerrahisi bir sıçan modeli üzerinde geliştirildi.

 

Keywords

• Endoprotez; hayvan modeli; heterotopik ossifikasyon; kalça; patojen.

A new small-animal model for the study of acquired heterotopic ossification after hip surgery

Abstract

Objective: Heterotopic ossification (HO)—the formation of bone in soft tissues—is a frequent problem after surgery of the hip and pelvis, but little is known about its underlying pathogenic mechanisms.It is vital to study the underlying pathogenesis in animal models to develop and evaluate new prophylactic regimens directed against HO. However, previously developed small-animal models for the study of HO imitate neither surgery nor trauma-mechanisms that potentially cause HO. Hence, the goal of this study was to develop a novel small-animal model imitating hip surgery that can reliably produce HO. Methods: Twenty male Wistar rats were subjected to surgery of the right hip during which the femoral canal was reamed in three steps up to 2 mm, and a muscle lesion was made. Twelve weeks after surgery, the amount of heterotopic bone was assessed using micro-computed tomography. Results: Eighteen of 20 animals showed HO around the hip 12 weeks after surgery. The amount of heterotopic bone varied from very small particles up to near ankylosis. Conclusion: A rat model of hip/pelvic surgery that does not use exogenous osteogenic stimulus and can reliably produce HO was developed.

Keywords

• Animal model
• endoprothesis
• heterotopic ossification
• hip
• pathogenesis

References

1. McCarthy EF, Sundaram M. Heterotopic ossification: a review. Skeletal Radiol 2005;34:609–19.
2. Vanden Bossche L, Vanderstraeten G. Heterotopic ossifi- cation: a review. J Rehabil Med 2005;37:129–36.
3. Shehab D, Elgazzar AH, Collier BD. Heterotopic ossifica- tion. J Nucl Med 2002;43:346–53.
4. Rommens PM, Broos PL, Vanderschot P. Preparation and technique for surgical treatment of 225 acetabulum frac- tures. 2 year results of 175 cases. [Article in German] Un- fallchirurg 1997;100:338–48.
5. Baird EO, Kang QK. Prophylaxis of heterotopic ossifica- tion - an updated review. J Orthop Surg Res 2009;4:12.
6. Griffin SM, Sims SH, Karunakar MA, Seymour R, Haines N. Heterotopic ossification rates after acetabular fracture surgery are unchanged without indomethacin prophylaxis. Clin Orthop Relat Res 2013;471:2776–82.
7. Ahrengart L. Periarticular heterotopic ossification after total hip arthroplasty. Risk factors and consequences. Clin Orthop Relat Res 1991;263:49–58.
8. Brooker AF, Bowerman JW, Robinson RA, Riley LH Jr. Ectopic ossification following total hip replacement. Inci- dence and a method of classification. J Bone Joint Surg Am

9. Ritter MA, Sieber JM. Prophylactic indomethacin for the prevention of heterotopic bone formation following total hip arthroplasty. Clin Orthop Relat Res 1985;196:217– 25.
10. Stover SL, Niemann KM, Tulloss JR. Experience with surgical resection of heterotopic bone in spinal cord injury patients. Clin Orthop Relat Res 1991;263:71–7.
11. Kan L, Kessler JA. Animal models of typical heterotopic ossification. J Biomed Biotechnol 2011;2011:309287.
12. McClure J. The effect of diphosphonates on heterotopic ossification in regenerating Achilles tendon of the mouse. J Pathol 1983;139:419–30.
13. Michelsson JE, Granroth G, Andersson LC. Myositis os- sificans following forcible manipulation of the leg. A rabbit model for the study of heterotopic bone formation. J Bone Joint Surg Am 1980;62:811–5.
14. Volek-Smith H, Urist MR. Recombinant human bone morphogenetic protein (rhBMP) induced heterotopic bone development in vivo and in vitro. Proc Soc Exp Biol Med 1996;211:265–72.
15. 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;25:506–10.
16. Hannallah D, Peng H, Young B, Usas A, Gearhart B, Hua- rd J. Retroviral delivery of Noggin inhibits the formation of heterotopic ossification induced by BMP-4, demineralized bone matrix, and trauma in an animal model. J Bone Joint Surg Am 2004;86-A:80–91.
17. Moed BR, Resnick RB, Fakhouri AJ, Nallamothu B, Wag- ner RA. Effect of two nonsteroidal antiinflammatory drugs on heterotopic bone formation in a rabbit model. J Arthro- plasty 1994;9:81–7.
18. Murat N, Hocaoglu N, Karatosun V, Yorukoglu K, Gidener S, Gunal I. The effects of non-selective and cy- clooxygenase-2-selective non-steroidal anti-inflammatory drugs on heterotopic ossification in rats. Med Sci Monit 2005;11:BR449–51.
19. Vanden Bossche LC, Van Maele G, Wojtowicz I, Bru I, Decorte T, De Muynck M, et al. Free radical scavengers versus methylprednisolone in the prevention of experi- mentally induced heterotopic ossification. J Orthop Res 2009;27:748–51.
20. Anthonissen J, Ossendorf C, Ritz U, Hofmann A, Rom- mens PM. Animal models for acquired heterotopic ossifi- cation. Acta Orthop Belg 2014;80:2–10.
21. Schneider DJ, Moulton MJ, Singapuri K, Chinchilli V, Deol GS, Krenitsky G, et al. The Frank Stinchfield Award. Inhibition of heterotopic ossification with radia- tion therapy in an animal model. Clin Orthop Relat Res 1998;355:35–46.
22. Tannous O, Stall AC, Griffith C, Donaldson CT, Castel- lani RJ Jr, Pellegrini VD Jr. Heterotopic bone formation about the hip undergoes endochondral ossification: a rab- bit model. Clin Orthop Relat Res 2013;471:1584–92.
23. Ritter MA, Vaughan RB. Ectopic ossification after total hip arthroplasty. Predisposing factors, frequency, and effect on results. J Bone Joint Surg Am 1977;59:345–51.
24. Thomas BJ. Heterotopic bone formation after total hip ar- throplasty. Orthop Clin North Am 1992;23:347–58.
25. Toom A, Suutre S, Märtson A, Haviko T, Selstam G, Ar- end A. Lack of a central role for osteoprogenitor cells from the femoral canal in heterotopic ossification of the hip: an experimental study in a rat model. J Bone Joint Surg Br
26. Pape HC, Marsh S, Morley JR, Krettek C, Giannoudis PV. Current concepts in the development of heterotopic ossifi- cation. J Bone Joint Surg Br 2004;86:783–7.
27. Nauth A, Giles E, Potter BK, Nesti LJ, O’brien FP, Bosse MJ, et al. Heterotopic ossification in orthopaedic trauma. J Orthop Trauma 2012;26:684–8.
28. Lin L, Shen Q, Xue T, Yu C. Heterotopic ossification in- duced by Achilles tenotomy via endochondral bone forma- tion: expression of bone and cartilage related genes. Bone 2010;46:425–31.