İlker Özeç

Effects of Simvastatin on Mandibular Distraction Osteogenesis

PURPOSE The aim of this study was to evaluate the effects of local and systemic simvastatin application on distraction osteogenesis. MATERIALS AND METHODS Eighteen New Zealand white rabbits underwent unilateral mandibular distraction osteogenesis. After 7 days of neutral fixation, 0.4 mm twice per day, distraction was performed for 10 days. Simvastatin was applied locally during the osteotomy phase with a gelatin sponge carrier and systemically during the distraction osteogenesis period by oral gavage. All animals were killed at the end of the consolidation period of 14 days. The distracted mandibles were harvested and evaluated by plain radiography, by peripheral quantitative computed tomography, and with histomorphometry. RESULTS Radiographic evaluation with peripheral quantitative computed tomography showed that the area of the regenerate increased by 9.6% in the local simvastatin group and by 19.3% in the systemic simvastatin group as compared with the control group. In both experimental groups the density of the regenerate increased by 6.7% as compared with the control group. Statistical evaluation of radiographic data showed that all of these changes were not significant. Histomorphometric evaluation determined that there was no statistical difference among groups with regard to the ratios of bone tissue volume to fibrous tissue volume and bone tissue volume to marrow tissue volume. CONCLUSIONS The results of this study suggest that simvastatins effect on enhancing distraction regenerate is limited with the applied doses and methods.

Is It Possible to Anesthetize Palatal Tissues With Buccal 4% Articaine Injection?

PURPOSE The aim of this study was to evaluate the presence of probable diffused local anesthetic solution at and anesthesia of palatal tissues after buccal injection of 4% articaine hydrochloride (HCl) with 1:100,000 epinephrine or 1:200,000 epinephrine at the premolar and molar region. MATERIALS AND METHODS Thirty volunteers received maxillary buccal injections of 4% articaine HCl with 1:100,000 epinephrine or 1:200,000 epinephrine bilaterally to the first premolar or first molar. Magnetic resonance images were obtained before and 5 minutes after local anesthetic injections, and a visual evaluation was done to determine the presence of local anesthetic solution at palatal tissues. Anesthesia of palatal tissues after buccal injection was assessed by needle-prick stimulation pain with a visual analog scale (VAS). The Kruskal-Wallis test was used for comparison of the VAS values. RESULTS The visual evaluation of the magnetic resonance images did not show any signal change as an indicator of the presence of local anesthetic solution at the palatal region. Most of the volunteers described moderate or severe pain with needle-prick stimulation. The mean VAS score for needle-prick stimulation was 86.33 +/- 39.45 mm (1:100,000 epinephrine) and 87.0 +/- 36.28 mm (1:200,000 epinephrine) in the first premolar region and 57.20 +/- 46.69 mm (1:100,000 epinephrine) and 75.53 +/- 49.78 mm (1:200,000 epinephrine) in the molar region (P > .05). CONCLUSION We could not establish the presence of anesthesia or 4% articaine HCl at the palatal tissues after buccal injection. Maxillary tooth removal without palatal injection requires further objective investigations.

The influence of rifamycin decontamination on incorporation of autologous onlay bone grafts in rats: A histometric and immunohistochemical evaluation

OBJECTIVE Although it has been shown that rifamycin is an effective agent for bone graft decontamination, no information exists on the effects of rifamycin decontamination on bone graft incorporation. The aim of this study was to evaluate the influence of rifamycin decontamination on the incorporation of autologous onlay bone grafts quantitatively. DESIGN In 30 rats, a standardized 5.0-mm-diameter bone graft was harvested from the right mandibular angle, contaminated with saliva, decontaminated with rifamycin solution, and augmented to the left as an onlay graft. Ten animals were sacrificed at 7, 14, and 21 days after surgery. In the control group (10 rats), the onlay grafts were neither contaminated nor decontaminated, and the rats were sacrificed at 21 days after surgery. Histological slides were prepared from each grafted site for both immunohistochemistry analysis (bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) antibodies) and histometric analysis. Images obtained from the graft incorporation area with the light microscope were transferred to a PC, and they were evaluated using Clemex PE 3.5 image analysis software. RESULTS The grafts were fully incorporated in all specimens. The results showed that rifamycin decontamination has no detrimental effect on graft incorporation and the findings revealed a tendency for earlier revascularization and osteogenesis in the decontamination group. Data were analyzed using variance analysis and Tukeys test. CONCLUSIONS Rifamycin decontamination has no detrimental effect on autogenous graft incorporation, and it can be used for graft decontamination with confidence.

Re: Statin-induced bone morphogenetic protein (BMP) 2 expression during bone regeneration: an immunohistochemical study

To the Editor: In their recent article, Alam et al. compared the osteoinductive activity of statin/atelocollagen sponge (ACS) implants and recombinant human bone morphogenetic protein 2 (rhBMP-2)/ACS implants in an immunohistochemical study. Because locally applied statins (specific inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the production of cholesterol) were discovered to be potent stimulators of bone formation by inducing BMP-2, these compounds were used as practical bone anabolic agents in different studies by several researchers, including us. Alam et al. used pravastatin, which is a member of the statin family as an anabolic agent. They showed the osteoinductive activity of statin/ACS implants but couldn’t observe new bone formation clearly. Statins differ in their lipophilicity/hydrophilicity, which reflects their potential to cross cellular membranes and their potency. Lipophilic statins, such as simvastatin, easily cross the cellular membrane to enter cells, but hydrophilic statins, such as pravastatin, rely on specific carrier mechanisms for entry into cells. In 2000, Sugiyama et al. reported that compactin and simvastatin, but not pravastatin, selectively induced human BMP-2 promoter activity, and they associated this result to pravastatin’s structure. I think this statement also explains why Alam et al. could not see new bone formation clearly at the fourth week. Further investigations are needed to confirm the effect of pravastatin on regeneration of hard tissue defects in vivo. Alam et al. determined no findings suggestive of inflammation at 10 mg local pravastatin application. I think this dose is very high for local statin application. It is known that local high-dose statin application causes considerable soft tissue inflammation. Stein et al. applied a single dose of 0.1, 0.5, 1.0, 1.5, or 2.2 mg simvastatin in methylcellulose gel on the lateral aspect of the mandible and determined that reducing simvastatin dose from 2.2 mg to 0.5 mg reduced inflammation to a more clinically acceptable level without sacrificing bone-growth potential. Lee et al. also confirmed that 0.5 mg statin produced the best bone growth/inflammation ratio. Pravastatin’s related inflammatory reactions also need further investigations. In the discussion section, Alam et al. wrote that Wong and Rabie reported newly formed bone observed after implantation of 10 mg simvastatin in rabbit bone defect. Wong and Rabie prepared a simvastatin solution at the concentration of 2.5 mg/mL by using a 10 mg simvastatin tablet and then used 0.2 mL from this solution to prepare the statin/collagen implant. I think the dose used in the Wong and Rabie’s work was misunderstood. In addition to their cholesterol-lowering activity, statins have pleiotropic effects, including antiinflammatory effect. Although statins have antiinflammatory effects, local high-dose statin application causes considerable inflammation. This conflict needs clarification to prevent future clinical problems.

Trombosit Zengin Fibrin ve Rifamisinin Bir Allogreft ile Kombinasyonda Kemik Büyütme Üzerindeki Etkilerinin Tavşan Tibiasında Eşzamanlı İmplant Yerleştirmesiyle Histomorfometrik Olarak Değerlendirilmesi

Amac: Yuksek profilli dental implant yerlestirilmesinde yonlendirilmis doku augmentasyonunu gelistirmek icin plateletten zengin fibrin (PRF) ve rifamisin uygulamasinin potansiyelinin degerlendirilmesi. Materyal ve metod: Iki mm’lik koronal kismi kemik disinda kalan dental implantlar kubbe seklinde sert kaplayici titanyum membran ile kapatilmis ve membranin ici demineralize dondurularak kurutulmus kemik allogrefti (DFDBA)+salin (7 tavsan), DFDBA+rifamisin (8 tavsan) veya DFDBA+PRF (8 tavsan) ile doldurulmustur. Bulgular: Kemik implant kontagi (KIK) salin grubunda 58.43±1.92%, rifamisin grubunda 68.34±20.37% ve PRF grubunda 80.70±2.55% olarak tespit edilmistir. Sirasiyla yeni kemik olusum yuzdesi de 36.90±0.94, 45.26±0.60 ve 51.82±0.82 olarak bulunmustur. Sonuc: Hem PRF hem de rifamisinin yonlendirilmis doku augmentasyonunu gelistirici potansiyeli oldugu ve yuksek profilli dental implant uygulamalarinda sert kaplayici titanyum membran altinda DFDBA + PRF veya DFDBA + rifamisin kullanilmasinin hem KIK degerini hem de yeni kemik olusum yuzdesini artirabilecegi gorulmustur.

EFFECT OF LOCAL RIFAMYCIN APPLICATION ON EXPRESSION OF BMP-2 AND BONE REGENERATION

Amac: Bu calismanin amaci lokal rifamisin uygulamasinin kemik iyilesmesi sirasinda BMP–2 salinimi uzerine etkisinin degerlendirilmesidir. Materyal ve method: Rat mandibula angulus bolgesinde standart olarak 5 mm capinda kritik boyutta kemik defektleri olusturulmustur. Kontrol grubunda (8 rat) defektlere herhangi bir uygulama yapilmamistir. Birinci deney grubunda (8 rat) defekt bolgesi rifamisin solusyonu ile irrige edildikten sonra, defekt bolgesine 1, 3 ve 7. gunlerde 25 mg rifamisin solusyonu enjekte edilmistir. Ikinci deney grubunda (8 rat) defekt bolgesi 25 mg rifamisin solusyonu ile karistirilmis gelatin sponge ile greftlenmistir. Cerrahiden 21 gun sonra ratlar sakrifiye edilmistir. Defekt bolgesinden hem immunhistokimyasal analiz (kemik morfogenetik protein –2 antibody) icin hem de histomorfometrik analiz icin histolojik kesitler hazirlanmistir. Elde edilen verilerin analizi Mann Whitney U ve Kruskall Wallis testi kullanilarak yapilmistir. Bulgular: Deney grubunda kontrol grubuna gore ortalama yeni kemik formasyonu, osteoblast sayisi ve yeni damar olusum sayisinda artis oldugu gorulmustur. Her iki deney grubunda da anti–bmp–2 ile isaretlenmenin (hucre sayma) kontrol grubuna gore daha fazla oldugu gorulmustur. Sonuc: Kritik boyutta kemik defektlerine lokal olarak rifamisin uygulamasinin BMP–2 salinimi uzerine pozitif etkileri oldugu tespit edilmistir.