Kritik boyutlu kemik defektlerinde denosumab ve ozon uygulamasının kemik iyileşmesi üzerine etkisinin araştırılması

Yıl 2024, Cilt: 25 Sayı: 2, 38 - 45, 28.06.2024

Ersin Keskin , Beyza Kaya , Ayfer Aktaş

Öz

Amaç: Maksillofasiyal cerrahide herhangi bir sebeple oluşan defektlerin iyileşmesini hızlandırmak amacıyla çeşitli ilaçlar kullanılmaktadır. Bu ilaçlar arasında osteoporoz hastalığında kullanılan bifosfonat grubu ilaçlardan denosumabın , yeni kemik oluşumu üzerinde olumlu etkileri olduğu çeşitli çalışmalarda gösterilmiştir. Genel tıp alanında ve dişhekimliğinde yaygın kullanımı olan ozon ise yine kemik yapımı üzerinde olumlu etkileri olan alternatif bir tedavi olarak son yıllarda yaygın olarak kullanılmaktadır. Bu çalışmanın amacı rat kalvaryumlarında oluşturulan kritik boyutlu defektlerde denosumab ve ozon uygulamaları yaparak, yeni kemik oluşumunun değerlendirilmesidir.
Gereç ve Yöntem: Çalışmamızda 40 adet Spraque Dawley cinsi erkek rat kullanıldı. Ratlar 4 gruba ayrıldı. Kontrol grubuna sadece greft konuldu. Ozon grubu (O) ve ozon ve denosumab (O-D) gruplarına greft uygulandıktan sonra 15 saniye süreyle topikal ozon uygulandı. Denosumab grubu (D) ve ozon ve denosumab(O-D) grubuna 8 hafta süresinde 4 haftada bir olmak üzere subkütan (s.c) 10 mg/kg Prolia(denosumab) enjekte edildi. Her gruptan 5 hayvan 4. hafta sonunda, grupdaki diğer 5 hayvan ise 8. hafta sonunda sakrifiye edildikten sonra histopatolojik incelemeler yapıldı. Gruplar arasındaki farklılıklar istatistiksel analizlerle değerlendirilmiştir.
Bulgular: Yapılan histopatolojik inceleme sonrası greft+ozon ve greft+denosumab uygulanan gruplarda sadece greft yerleştirilen kontrol grubuna kıyasla daha iyi kemik oluşumu gözlendi. Kontrol grubu dışındaki diğer gruplar birbirleriyle kıyaslandığında istatistiksel olarak anlamlı bir fark olmasa da denosumab uygulanan gruplarda ozon grubuna göre daha fazla yeni kemik oluşumu belirlendi.
Sonuç: Çalışmamızın sonucunda ozon ve denosumab uygulamasının yeni kemik yapımı üzerine olumlu katkısı olduğunu ancak bu konuda daha fazla çalışma yapılması gerektiğini düşünmekteyiz.

Anahtar Kelimeler

Rat, ozon, denosumab, yeni kemik yapımı

Investigation of the effect of denosumab and ozone application on bone healing in critical size bone defects

Öz

Aims: In maxillofacial surgery, various drugs are used in order to accelerate the recovery of defects caused by any reason. Several studies have shown that denosumab from bisphosphonate group drugs used in osteoporosis patients has positive effects on new bone formation. In general medicine and dentistry, ozone is in widespread use as an alternative treatment and has positive effects on new bone formation. The aim of this study was to evaluate new bone formation by performing denosumab and ozone on critical-sized rat calvarium defects.
Methods: In our study, 40 Sprague Dawley rats were used. Rats were divided into 4 groups. Only grafts were placed in the control group. After applying graft to ozone group (O) and ozone and denosumab (O-D) groups, topical ozone was applied for 15 seconds. Denosumab group (D) and O-D group were injected subcutaneously (s.c) 10 mg/kg Prolia (denosumab) every 4 weeks for 8 weeks. 5 animals from each group at the end of week 4, while the other five animals in the group at the end of 8 weeks after being sacrificed for histopathological examination was performed. The differences between the groups were evaluated by statistical analysis.
Results: After histopathological examination, better bone formation was observed in the ozone and denosumab treated groups compared to the control group. There was no statistically significant difference between the groups except for the control group, however, new bone formation was determined in the groups treated with denosumab compared to the ozone group.
Conclusion: As a result of our study, we believe that the application of ozone and denosumab has a positive effect on the formation of new bone, but more comprehensive studies on the subject are needed.

Anahtar Kelimeler

Rat, ozone, denosumab, new bone formation

Kaynakça

• Guler R, Dundar S, Bozoglan A, et al. The biomechanical investigation of osseointegration levels in titanium implants simultaniously placed with different bone grafts. Niger J Clin Pract. 2024;27:310 316.
• Korkmaz H, Küçükkolbaşı H. Ozone applications in dentistry. J Dent Fac Ataturk Uni. 2013;7:125-134.
• Gartner LP, Hiatt James I. Color Textbook of Histology 3rd edition. Saunders Elsevier, 2007,114-130.
• Schenk Robert K. Biology of fracture. In: Browner B, Jupiter J, Levine A, Trafton P (Eds) Skeletal Trauma. Saunders, Philadelphia. 2003;1:29-74.
• Kılıçoğlu SS. Fracture healing on microscobic level. Ank Üni Tıp Fak Mec. 2002;55(2):143-150.
• ElHawary H, Baradaran A, Abi-Rafeh J, Vorstenbosch J, Xu L, Ionut Efanov J. Bone healing and inflammation: principles of fracture and repair. Semin Plast Surg. 2021; 35(03):198-203. DOI: 10.1055/s-0041-1732334
• Kendler DL, Cosman F, Stad RK, Ferrari S. Denosumab in the treatment of osteoporosis: 10 years later: a narrative review. Adv Ther. 2022;39:58-74. https://doi.org/10.1007/s12325-021-01936-y
• Colella A, Yu E, Sambrook P, BAgSci TH, Goss A. What is the risk of developing osteonecrosis following dental extractions for patients on denosumab for osteoporosis? J Oral Maxillofac Surg. 2023;81(2):232-237.
• McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354:821-831.
• Bocci V. Scientific and medical aspects of ozone therapy. state of the art. Arch Med Res. 2006;37(4):425-435.
• Polydorou O, Halili A, Wittmer A, Pelz K, Hahn P. The antibacterial effect of gas ozone after 2 months of in vitro evaluation. Clin Oral Investig. 2012;16:545-550.
• Huth KC, Jakob FM, Saugel B et al. Effect of ozone on oral cells compared with established antimicrobials. Eur J Oral Sci. 2006;114(5):435-440.
• Polydorou O, Pelz K, Hahn P. Antibacterial effect of an ozone device and its comparison with two dentin-bonding systems. Eur J Oral Sci. 2006;114(4):349-353.
• Baysan A, Lynch E. Effect of ozone on the oral microbiota and clinical severity of primary root caries. Am J Dent. 2004; 17(1):56-60.
• Azarpazhooh A, Limeback H. The application of ozone in dentistry: a systematic review of literature. J Dent. 2008;36(2):104-116.
• Das S. Application of ozone therapy in dentistry. Indian J Dent Adv. 2011; 3(2): 538-542.
• Kazancioglu HO, Kurklu E, Ezirganli S. Effects of ozone therapy on pain, swelling, and trismus following third molar surgery. Int J Oral Maxillofac Surg. 2014;43(5):644.
• Agın Demircan H, Gunes N, Guler R. A comparative investigation of the effects of resveratrol and dental pulp delivered mesenchimal stem cells on rat tibia bone defect healing. Revista Científica. 2024;34(2):rcfcv-e34372. Doi: 10.52973/rcfcv-e34372
• Ominsky L. Denosumab, a fully human RANKL antibody, reduced bone turnover markers and increased trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys. Bone J. 2011;49(2):162-173.
• HelaS A. Inhibition of receptor activator of NF-B Ligandby Denosumab Attenuates Vascular Calcium Deposition in Mice. Am J Pathol. 2009; 175(2):473-478.
• Kostenuik PJ. Effects of denosumab, alendronate, or denosumab following alendronate on bone turnover, calciumhomeostasis, bone mass and bone strength in ovariectomized cynomolgus monkeys. J Bone Miner Res. 2015;30(4):657-669.
• Kurban S, Mehmetoğlu İ. Osteoprotegerin, rank and rank ligand. Turkish J Biochemist. 2007;32(4):178-184.
• Suresh, Abrahamsen B. Denosumab: a novel antiresorptive drug for osteoporosis. Cleve Clin J Med. 2015;82(2):105-114.
• Alpan, AL, Toker H, Ozer H. Ozone therapy enhances osseous healing in rats with diabetes with calvarial defects: a morphometric and immunohistochemical study. J periodontal. 2016;87(8):982-989.
• Buyuk SK, Ramoglu SI, Sonmez MF. The effect of different concentration of topical ozone administration on bone formation in orthopedically expanded suture in rats. Eur J Orthod. 2016; 38(3):281-285.
• Gerstenfeld LC. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Miner Res. 2009;24:196-208.
• Bernhardsson D. Anti-RANKL treatment improves screw fixation in cancellous bonein rats. Inter J Care Injur. 2015;46:990-995.