Rekombinant insan epidermal büyüme faktörü (rhEGF) ve alendronat sodyumun sıçanlarda tibial kirik iyileşmesi üzerindeki etkilerinin karşılaştırılması: deneysel çalışma

Year 2024, Volume: 49 Issue: 3, 703 - 711, 30.09.2024

Hüseyin Emre Tepedelenlioğlu , Ferid Abdullaliyev , Asim Ahmadov , Saadet Özen Akarca Dizakar , Candan Özoğul , Erdinç Esen

https://doi.org/10.17826/cumj.1490881

Abstract

Amaç: Bu çalışmanın amacı rekombinant insan epidermal büyüme faktörünün (rhEGF) kemik iyileşmesi üzerindeki etkilerini pratikte yaygın olarak kullanılan bir bifosfonat olan alendronat ile karşılaştırmaktır.
Gereç ve Yöntem: Osteotom ile 24 Sprague-Dawley sıçanın tibial şaftında iyatrojenik kırık oluşturuldu ve intramedüller Kirschner teli (K-teli) ile tespit edildi. Operasyondan sonra, Grup 1'e postoperatif 1 günden 28. güne kadar 0,2 mg/kg/gün oral alendronat sodyum, Grup 2'ye postoperatif 1 ve 14. günlerde tek doz 0,5 mg/kg intraosseöz rhEGF verilmiş ve Grup 3 ise toplam dört hafta boyunca oral salin ile takip edilmiştir. Dördüncü haftanın sonunda hayvanlara ötenazi uygulandı ve alt ekstremiteler kallusa zarar vermeden yumuşak dokuları sıyrılarak çıkarıldı. Gruplara ait doku örnekleri hazırlandı ve hematoksilen-eozin ile boyandı. Boyama sonrasında kaynama derecesini değerlendirmek için histolojik skorlama yapıldı.
Bulgular: Alendronat sodyum grubu ortalama 6.95± 1.28 histolojik skor gösterdi. RhEGF grubunun ortalama skoru 4.85±1.66 ile daha düşüktü. Plasebo grubu 4.10±1.68 ortalama skor ile kemik iyileşmesinde en az ilerleme gösteren grup olmuştur. Alendronat sodyum grubunda histolojik skor hem rhEGF hem de plasebo gruplarına kıyasla anlamlı derecede yüksekti. Skorlar açısından rhEGF ve plasebo grupları arasında da istatistiksel olarak anlamlı bir fark vardı.
Sonuç: Alendronat sodyum sıçanlarda kırık iyileşme süreçlerini geliştirmiştir. rhEGF'nin kemik iyileşmesindeki rolü daha fazla araştırma gerektirmektedir. Kemik iyileşmesinde bifosfonatlar ve büyüme faktörlerinin anlaşılması geliştikçe, ortopedik ortamlarda hasta bakımını optimize etmek için stratejilerin geliştirilmesi beklenmektedir.

Keywords

Bisfosfonat, rhEGF, Kırık İyileşmesi

Ethical Statement

-

Supporting Institution

-

Project Number

-

Thanks

-

Comparison of the effects of recombinant human epidermal growth factor (rhEGF) and alendronate sodium on tibial fracture healing in rats: an experimental study

Abstract

Purpose: The objective of this study is to compare the effects of recombinant human epidermal growth factor (rhEGF) on bone healing with those of alendronate, a bisphosphonate widely used in practice.
Materials and Methods: An iatrogenic fracture was created in the tibial shaft of 24 Sprague-Dawley rats with osteotome and fixed with an intramedullary Kirschner wire (K-wire). After surgery, Group 1 was given 0.2 mg/kg/day of oral alendronate sodium on postoperative Day 1 to 28, Group 2 received a single dose of 0.5 mg/kg of intraosseous rhEGF on postoperative Days 1 and 14, and Group 3 was followed for a total of four weeks with oral saline. At the end of Week 4, the animals were euthanized and the lower extremities were removed by stripping the soft tissues without damaging the callus. Tissue samples of groups were prepared and and stained with hematoxylin-eosin. After staining, histological scoring was performed to evaluate the degree of union.
Results: Alendronate sodium group demonstrated a mean histological score of 6.95± 1.28. The rhEGF group had a lower mean score of 4.85±1.66. The placebo group exhibited the least progress in bone healing with a mean score of 4.10±1.68. The histological score was significantly higher in the alendronate sodium group compared to both the rhEGF and placebo groups. There was also a statistically significant difference between the rhEGF and placebo groups in terms of scores.
Conclusion: Alendronate sodium enhanced fracture healing processes in rats. The role of rhEGF in bone healing requires further exploration. As the understanding of bisphosphonates and growth factors in bone healing evolves, the strategies for optimizing patient care in orthopedic settings are expected to be developed.

Keywords

bisphosphanate, rhEGF, Fracture, Nonunion, Bone Healing

Ethical Statement

-

Supporting Institution

-

Project Number

-

Thanks

-

References

• Claes LE. Mechanobiology of Fracture Healing: From Basic Science To Clinical Application. Cham, Springer, 2022.
• Giannoudis PV, Einhorn TA, Marsh D. Fracture healing: the diamond concept. Injury. 2007;38:S3-6.
• Birinci Ş, Bingol I, Bakırcıoğlu S, Oral M, Yılmaz ET, Yaşar NE et al. Improving health-care planning for fracture patients in Türkiye: insights from a nationwide study. Ulus Travma Acil Cerrahi Derg. 2023;29:1184-90.
• Dong Y, Zhang Y, Song K, Kang H, Ye D, Li F. What was the epidemiology and global burden of disease of hip fractures from 1990 to 2019? Results from and additional analysis of the global burden of disease study 2019. Clin Orthop Relat Res. 2023;481:1209-20.
• Harris E, Clement N, MacLullich A, Farrow L. The impact of an ageing population on future increases in hip fracture burden. Bone Joint J. 2024;106-B(1):62-8.
• Perut F, Roncuzzi L, Gómez-Barrena E, Baldini N. Association between bone turnover markers and fracture healing in long bone non-union: a systematic review. J Clin Med. 2024;13:2333.
• Bowers KM, Anderson DE. Delayed union and nonunion: current concepts, prevention, and correction: a review. Bioengineering. 2024;11:525.
• Donié C, Reumann MK, Hartung T, Braun BJ, Histing T, Endo S et al. Predictive model development to identify failed healing in patients after non-union fracture surgery. arXiv preprint arXiv. 2024:240411760.
• Wildemann B, Ignatius A, Leung F, Taitsman LA, Smith RM, Pesántez R et al. Non-union bone fractures. Nat Rev Dis Primers. 2021;7:57.
• Virk MS, Lieberman JR. Biologic adjuvants for fracture healing. Arthritis Res Ther. 2012;14:225.
• Nauth A, Lee M, Gardner MJ, Brinker MR, Warner SJ, Tornetta P, 3rd et al. Principles of nonunion management: state of the art. J Orthop Trauma. 2018;32:52-7.
• Toğral G, Arıkan M, Korkusuz P, Hesar RH, Ekşioğlu MF. Positive effect of tadalafil, a phosphodiesterase-5 inhibitor, on fracture healing in rat femur. Eklem Hastalik Cerrahisi. 2015;26:137-44.
• Gao Y, Liu X, Gu Y, Song D, Ding M, Liao L et al. The effect of bisphosphonates on fracture healing time and changes in bone mass density: a meta-analysis. Front Endocrinol (Lausanne). 2021;12:688269.
• Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799-809.
• Aki T, Hashimoto K, Uozumi H, Saito M, Sugawara K, Suzuki M et al. Morphological and morphometrical analyses of fracture-healing sites of an atypical femoral fracture in patients with and without long-term bisphosphonate treatment for osteoporosis: a report of two cases. Tohoku J Exp Med. 2021;253:261-7.
• Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294-301.
• Huo MH, Troiano NW, Pelker RR, Gundberg CM, Friedlaender GE. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res. 1991;9:383-90.
• Prinsloo P, Hosking D. Alendronate sodium in the management of osteoporosis. Ther Clin Risk Manag. 2006;2:235-49.
• Kates SL, Ackert-Bicknell CL. How do bisphosphonates affect fracture healing? Injury. 2016;47:65-8.
• Garcia-Orue I, Gainza G, Gutierrez FB, Aguirre JJ, Evora C, Pedraz JL et al. Novel nanofibrous dressings containing rhEGF and Aloe vera for wound healing applications. Int J Pharm. 2017;523:556-66.
• Oh H, Seong J, Kim W, Park S, Koom WS, Cho NH et al. Recombinant human epidermal growth factor protects radiation-induced intestine injury in murine system. J Radiat Res. 2010;51:535-41.
• Naji MA, Marzook H, El Qashty RMN, Abdel-Rahman FH. Comparison between effect of bisphosphonates, concentrated growth factors or combination on rabbits' tibial bone defects healing: an experimental study. J Contemp Dent Pract. 2022;23:572-81.
• Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc. 2008;2008:pdb.prot4986.
• Han Z, Bhavsar M, Leppik L, Oliveira KMC, Barker JH. Histological scoring method to assess bone healing in critical size bone defect models. Tissue Eng Part C Methods. 2018;24:272-9.
• Bishop JA, Palanca AA, Bellino MJ, Lowenberg DW. Assessment of compromised fracture healing. J Am Acad Orthop Surg. 2012;20:273-82.
• Hegde V, Jo J, Andreopoulou P, Lane J. Effect of osteoporosis medications on fracture healing. Osteoporos Int. 2016;27:861-71.
• Fink EE, Ianssen T, Elling HE. IV. zoledronic acid promotes healing of complicated stress fractures in the foot. Bone Abstracts. 2016;5.
• Roy V, Pandey D, Shah V, N.G H, Ahmed J. Effect of bisphosphonates on fracture healing among the elderly people with intertrochanteric fracture. International Journal of Scientific Research. 2023;12:56-7.
• Reid IR. Bisphosphonates: new indications and methods of administration. Curr Opin Rheumatol. 2003;15:458-63.
• Ayanaoğlu T, Atik O, Tokgöz N, Uçar M. Sacral and pubic insufficiency fractures due to bisphosphonate treatment. Eklem Hastalik Cerrahisi. 2015;26:120-4.
• Yüce MO, Adalı E, Işık G. The effect of concentrated growth factor in the surgical treatment of medication-related osteonecrosis of the jaw in osteoporosis patients: a randomized controlled study. Clin Oral Investig. 2021;25:4529-41.
• Basal O, Atay T, Ciris İ M, Baykal YB. Epidermal growth factor promotes bone healing in surgically induced osteonecrosis of the femoral head . Bosn J Basic Med Sci. 2018;18:352-60.
• Li N, Cornelissen D, Silverman S, Pinto D, Si L, Kremer I et al. An updated systematic review of cost-effectiveness analyses of drugs for osteoporosis. Pharmacoeconomics. 2021;39:181-209.
• Romero Prada M, Roa C, Alfonso P, Acero G, Huérfano L, Vivas-Consuelo D. Cost-effectiveness analysis of the human recombinant epidermal growth factor in the management of patients with diabetic foot ulcers. Diabet Foot Ankle. 2018;9:1480249.