scholarly journals Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration

2021 ◽  
Vol 22 (23) ◽  
pp. 12823
Author(s):  
Yukie Tanaka ◽  
Kyaw Thu Aung ◽  
Mitsuaki Ono ◽  
Akihiro Mikai ◽  
Anh Tuan Dang ◽  
...  

Medication-related osteonecrosis of the jaw (MRONJ) is related to impaired bone healing conditions in the maxillomandibular bone region as a complication of bisphosphonate intake. Although there are several hypotheses for the onset of MRONJ symptoms, one of the possible causes is the inhibition of bone turnover and blood supply leading to bone necrosis. The optimal treatment strategy for MRONJ has not been established either. BMP-2, a member of the TGF-β superfamily, is well known for regulating bone remodeling and homeostasis prenatally and postnatally. Therefore, the objectives of this study were to evaluate whether cyclophosphamide/zoledronate (CY/ZA) induces necrosis of the bone surrounding the tooth extraction socket, and to examine the therapeutic potential of BMP-2 in combination with the hard osteoinductive biomaterial, β-tricalcium phosphate (β-TCP), in the prevention and treatment of alveolar bone loss around the tooth extraction socket in MRONJ-like mice models. First, CY/ZA was intraperitoneally administered for three weeks, and alveolar bone necrosis was evaluated before and after tooth extraction. Next, the effect of BMP-2/β-TCP was investigated in both MRONJ-like prevention and treatment models. In the prevention model, CY/ZA was continuously administered for four weeks after BMP-2/β-TCP transplantation. In the treatment model, CY/ZA administration was suspended after transplantation of BMP-2/β-TCP. The results showed that CY/ZA induced a significant decrease in the number of empty lacunae, a sign of bone necrosis, in the alveolar bone around the tooth extraction socket after tooth extraction. Histological analysis showed a significant decrease in the necrotic alveolar bone around tooth extraction sockets in the BMP-2/β-TCP transplantation group compared to the non-transplanted control group in both MRONJ-like prevention and treatment models. However, bone mineral density, determined by micro-CT analysis, was significantly higher in the BMP-2/β-TCP transplanted group than in the control group in the prevention model only. These results clarified that alveolar bone necrosis around tooth extraction sockets can be induced after surgical intervention under CY/ZA administration. In addition, transplantation of BMP-2/β-TCP reduced the necrotic alveolar bone around the tooth extraction socket. Therefore, a combination of BMP-2/β-TCP could be an alternative approach for both prevention and treatment of MRONJ-like symptoms.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae-Young Kim ◽  
Hyo-Won Jang ◽  
Jung-In Kim ◽  
In-Ho Cha

AbstractThe purpose of this study was to investigate the effect of administering intermittent parathyroid hormone (iPTH) before tooth extraction versus after tooth extraction on the risk of developing MRONJ in experimental animal model. Twenty-five ovariectomized rats received 6 weeks of bisphosphonate therapy. They were classified into 3 groups, based on the timing of the medication, as Control, Pre-PTH and Post-PTH groups. For Control group, normal saline was administered before and after tooth extraction. iPTH was administered during 4 weeks before tooth extraction for Pre-PTH group and after tooth extraction for Post-PTH group. The animals were euthanized 8 weeks after tooth extraction. Macroscopic, histological, micro-computed tomography (micro-CT), and histomorphometric examinations were conducted. The incidences of impaired healing were 11.11% both in Pre-PTH and Post-PTH groups, which was lower than the Control group (42.86%). Bone healing in the extraction socket, based on micro-CT and histomorphometry evaluations, was best in Post-PTH and worst in Control group. The Pre-PTH group showed moderate healing pattern. Despite of limitations in this study, the authors identified Pre-PTH group seems to have positive effect on extraction socket healing. With regard to timing, administering iPTH after tooth extraction was superior to applying it before tooth extraction.


Author(s):  
Michael Josef Kridanto Kamadjaja ◽  
Sherman Salim ◽  
Birgitta Dwitya Swastyayana Subiakto

Objective: This study was to determine OPG and RANKL expression after hydroxyapatite (HA) scaffold from crab shells (Portunus pelagicus) application in tooth socket of Cavia cobaya. Methods: This study was a post-test only control group design. Twenty four Cavia cobaya was divided into 4 groups. The lower left incisor was extracted and given a combination of HA and gelatin scaffold. Experimental animals were sacrificed on the 7th and 14th day. The amount of OPG and RANKL expression was calculated under a light microscope at 1000x magnification. The statistical analysis was done by One Way ANOVA Test and Tukey HSD. Results: Compared to other groups, the lowest and the highest level of OPG and RANKL were in P14 group. Conclusion: HA scaffold from crab shells (Portunus pelagicus) can increase OPG expression and decrease RANKL expression in the process of regenerating alveolar bone after tooth extraction.


2017 ◽  
Vol 50 (1) ◽  
pp. 36
Author(s):  
Bayu Indra Sukmana ◽  
Theresia Indah Budhy ◽  
I Gusti Aju Wahju Ardani

Background: The main oral health problem in Indonesia is the high number of tooth decay. Tooth extraction is the treatment often received by patients who experience tooth decay and the wound caused by alveolar bone resorption. Bark of Mangifera casturi has been studied and proven to contain secondary metabolite which has the ability to increase osteoblast’s activity and suppress osteoclast’s activity. Purpose: The purpose of this study was to analyze interleukin-1 beta (IL-1β) and bone morphogenic protein-2 (BMP-2) activities during bone remodeling after Mangifera casturi’s bark extract treatment. Method: This study was laboratory experimental research with randomized post-test only control group design. The Mangifera casturi bark was extracted using 96% ethanol maceration and n-hexane fractionation. This study used 40 male Wistar rats which are divided into 4 groups and the tooth extraction was performed on the rats’ right mandible incisive tooth. The four groups consisted of 6.35%, 12.7%, 25.4% extract treatment group, and a control group. Wistar’s mandibles were decapitated on the 7th and 14th day after extraction. Antibody staining on preparations for the examination of IL-1β and BMP-2 expressions was done using immunohistochemistry. Result: There was a significant difference of IL-1β and BMP-2 expressions in 6,35%, 12,7%, and 25,4% treatment groups compared to control group with p<0.05. Conclusion: Mangifera casturi’s bark extract was able to suppress the IL-1β expression and increase the BMP-2 expression during bone remodeling after tooth extraction.


2021 ◽  
Vol 24 (1) ◽  
pp. 1-5
Author(s):  
Olivia Avriyanti Hanafiah ◽  
Denny Satria ◽  
Avi Syafitri

Tooth extraction is a process of removing teeth from the alveolar bone. In wound healing, fibroblast are very important cells. The main purpose of this study was to determine the effect of mobe leaf 1% and 3% extract gel (Artocarpus lakoocha) on fibroblast proliferation in post extraction tooth socket wound healing. This research used 16 samples of wistar rats, divided into 4 groups, a positive control group, a negative control group and a 1% and 3% mobe leaf extract gel group. The left mandibular incisors were extracted, then 1% and 3% gels of mobe leaf extract were applied on day 1 to day 7. Data analysis was calculated using the Kruskal-Wallis test on clinical data and one way ANOVA test for microscopic. The result of the socket wound healing activity test for a good concentration of mobe leaf extract gel was 3%. This research shows significant resultith p-value of 0.018 (< 0.05) on the closure of the socket wound clinically which means the closure of the wound accelerates because of the mobe leaf 3% extract gel treatment. The distance of fibroblast on microscopically shows significant resultith a p-value of 0.002 (< 0.05), which means that there was an enlargement of the distance fibroblast at the socket wound closure with application of mobe leaf 3% extract gel. From the results of the study it can be concluded that mobe leaf 3% extract gel has the best ability to show acceleration the closure of the socket wound either clinically or microscopically.


2020 ◽  
Vol 99 (4) ◽  
pp. 402-409 ◽  
Author(s):  
G. Avila-Ortiz ◽  
M. Gubler ◽  
M. Romero-Bustillos ◽  
C.L. Nicholas ◽  
M.B. Zimmerman ◽  
...  

Alveolar ridge preservation (ARP) therapy is indicated to attenuate the physiologic resorptive events that occur as a consequence of tooth extraction with the purpose of facilitating tooth replacement therapy. This randomized controlled trial was primarily aimed at testing the efficacy of ARP as compared with unassisted socket healing. A secondary objective was to evaluate the effect that local phenotypic factors play in the volumetric reduction of the alveolar bone. A total of 53 subjects completed the study. Subjects were randomized into either the control group, which involved only tooth extraction (EXT n = 27), or the experimental group, which received ARP using a combination of socket grafting with a particulate bone allograft and socket sealing with a nonabsorbable membrane (dPTFE) following tooth extraction (ARP n = 26). A set of clinical, linear, volumetric, implant-related, and patient-reported outcomes were assessed during a 14-wk healing period. All linear bone assessments (horizontal, midbuccal, and midlingual reduction) revealed that ARP is superior to EXT. Likewise, volumetric bone resorption was significantly higher in the control group (mean ± SD: EXT = −15.83% ± 4.48%, ARP = −8.36% ± 3.81%, P < 0.0001). Linear regression analyses revealed that baseline buccal bone thickness is a strong predictor of alveolar bone resorption in both groups. Interestingly, no significant differences in terms of soft tissue contour change were observed between groups. Additional bone augmentation to facilitate implant placement in a prosthetically acceptable position was deemed necessary in 48.1% of the EXT sites and only 11.5% of the ARP sites ( P < 0.004). Assessment of perceived postoperative discomfort at each follow-up visit revealed a progressive decrease over time, which was comparable between groups. Although some extent of alveolar ridge remodeling occurred in both groups, ARP therapy was superior to EXT as it was more efficacious in the maintenance of alveolar bone and reduced the estimated need for additional bone augmentation at the time of implant placement (ClinicalTrials.gov NCT01794806).


2020 ◽  
Vol 21 (19) ◽  
pp. 7028
Author(s):  
Akihiro Mikai ◽  
Mitsuaki Ono ◽  
Ikue Tosa ◽  
Ha Thi Thu Nguyen ◽  
Emilio Satoshi Hara ◽  
...  

Medication-related osteonecrosis of the jaw (MRONJ) is a severe pathological condition associated mainly with the long-term administration of bone resorption inhibitors, which are known to induce suppression of osteoclast activity and bone remodeling. Bone Morphogenetic Protein (BMP)-2 is known to be a strong inducer of bone remodeling, by directly regulating osteoblast differentiation and osteoclast activity. This study aimed to evaluate the effects of BMP-2 adsorbed onto beta-tricalcium phosphate (β-TCP), which is an osteoinductive bioceramic material and allows space retention, on the prevention and treatment of MRONJ in mice. Tooth extraction was performed after 3 weeks of zoledronate (ZA) and cyclophosphamide (CY) administration. For prevention studies, BMP-2/β-TCP was transplanted immediately after tooth extraction, and the mice were administered ZA and CY for an additional 4 weeks. The results showed that while the tooth extraction socket was mainly filled with a sparse tissue in the control group, bone formation was observed at the apex of the tooth extraction socket and was filled with a dense connective tissue rich in cellular components in the BMP-2/β-TCP transplanted group. For treatment studies, BMP-2/β-TCP was transplanted 2 weeks after tooth extraction, and bone formation was followed up for the subsequent 4 weeks under ZA and CY suspension. The results showed that although the tooth extraction socket was mainly filled with soft tissue in the control group, transplantation of BMP-2/β-TCP could significantly accelerate bone formation, as shown by immunohistochemical analysis for osteopontin, and reduce the bone necrosis in tooth extraction sockets. These data suggest that the combination of BMP-2/β-TCP could become a suitable therapy for the management of MRONJ.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Beatriz Hernández-Monjaraz ◽  
Edelmiro Santiago-Osorio ◽  
Edgar Ledesma-Martínez ◽  
Itzen Aguiñiga-Sánchez ◽  
Norma Angélica Sosa-Hernández ◽  
...  

Periodontal disease (PD) is one of the main causes of tooth loss and is related to oxidative stress and chronic inflammation. Although different treatments have been proposed in the past, the vast majority do not regenerate lost tissues. In this sense, the use of dental pulp mesenchymal stem cells (DPMSCs) seems to be an alternative for the regeneration of periodontal bone tissue. A quasi-experimental study was conducted in a sample of 22 adults between 55 and 64 years of age with PD, without uncontrolled systemic chronic diseases. Two groups were formed randomly: (i) experimental group (EG) n=11, with a treatment based on DPMSCs; and a (ii) control group (CG) n=11, without a treatment of DPMSCs. Every participant underwent clinical and radiological evaluations and measurement of bone mineral density (BMD) by tomography. Saliva samples were taken as well, to determine the total concentration of antioxidants, superoxide dismutase (SOD), lipoperoxides, and interleukins (IL), before and 6 months after treatment. All subjects underwent curettage and periodontal surgery, the EG had a collagen scaffold treated with DPMSCs, while the CG only had the collagen scaffold placed. The EG with DPMSCs showed an increase in the BMD of the alveolar bone with a borderline statistical significance (baseline 638.82±181.7 vs. posttreatment 781.26±162.2 HU, p=0.09). Regarding oxidative stress and inflammation markers, salivary SOD levels were significantly higher in EG (baseline 1.49±0.96 vs. 2.14±1.12 U/L posttreatment, p<0.05) meanwhile IL1β levels had a decrease (baseline 1001.91±675.5vs. posttreatment 722.3±349.4 pg/ml, p<0.05). Our findings suggest that a DPMSCs treatment based on DPMSCs has both an effect on bone regeneration linked to an increased SOD and decreased levels of IL1β in aging subjects with PD.


2022 ◽  
Author(s):  
Siying Li ◽  
Hongyi Yang ◽  
Qinyu Duan ◽  
Hongyu Bao ◽  
Aodi Li ◽  
...  

Abstract Background:Autologous platelet concentrate has been widely used to encourage the regeneration of hard and soft tissues. Up to now, there are three generations of autologous platelet concentrates. Many studies have shown that different autologous platelet concentrates have different healing effects. However, these differences still need to be further verified and discussed. The purpose of this study was to explore and compare the effects of platelet-rich fibrin, concentrated growth factor and platelet-poor plasma on the healing of tooth extraction sockets in New Zealand rabbits. Methods:A total of 24 healthy male New Zealand white rabbits aged 8-12 weeks were selected. The experimental animals were randomly divided into four groups: three experimental groups were respectively implanted with PPP, CGF and PRF gel after bilateral mandibular anterior teeth were extracted, and the control group did not implant any material. The alveolar bone of the mandibular anterior region was taken at 2, 4 and 8 weeks after operation. The height and width of the extraction wound were detected by CBCT, the growth of the new bone was observed by HE and Masson staining, and the expression of osteogenic genes was detected by real-time PCR. Data were analyzed using IBM SPSS statistical package 22.0.Results: The radiological results showed that alveolar bone absorption in all groups gradually increased over time. However, the experimental groups showed lower amounts of bone absorption. The histological results showed that new bone formation was observed in all groups. Over time, the new bone trabeculae of the CGF group became closely aligned while those in the PPP and PRF groups remained scattered. PCR results showed that the expression of BMP-2 and ALP was higher in the experimental groups than the control group.Conclusion: In conclusion, the application of PRF, CGF and PPP in tooth extraction sockets effectively promoted bone regeneration. CGF showed more effective bone induction and tissue regeneration ability in the long term.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2398-2398
Author(s):  
André Pelegrini ◽  
Maria Elvira P Corrêa ◽  
Thiago Oliveira ◽  
Carmino De Souza ◽  
José Francisco Marques

Abstract Abstract 2398 Introduction: Autologous bone marrow has mesenchymals stem cells that can differentiate into osteoblasts. Therefore, the use of these cells in bone reconstruction therapy is becaming promising. Purpose: The first aim of this study was to evaluate the potential of autologous bone marrow graft aspirate containing mesenchymal stem cells in preserving the alveolar ridges following tooth extraction. A second aim was to clinically and radiographically evaluate the outcomes of dental implants installed in the healed sockets after one year in function. Methods: 13 healthy patients requiring upper anterior teeth extractions were enrolled in this study. They were randomized into two groups: Test group: 7 patients (n = 15 teeth); Control group: 6 patients (n = 15 teeth). 5 ml of autologous bone marrow from the iliac posterior crest were collected by haematologists immediately before the extractions and it was placed in alveolar sockets right after the teeth extractions in the test group. Nothing was grafted in the control sites. Following tooth extraction and evaluation of a buccal full-thickness flap, titanium screws were positioned throughout the buccal to the palatal plate and were used as reference points for measuring purposes. After 6 months, the sites were re-opened and bone loss measurements for thickness and height were taken. Additionally, prior to implant placement, bone cores were harvested and prepared for histologic and histomorphometric evaluation. Data of clinical probing and radiographic analysis were done in all sites after 1 year of follow up. Results: The test group had better results in preserving alveolar ridges for thickness showing 1.14+0.87mm of bone loss compared with the control group that showed 2.46+0.4mm (P<0.05). The test group showed also a less height of bone loss on the buccal plate, 0.62+0.51 and 1.17+0.26mm, respectively (P<0.05). Complimentary procedures were required before install the implants in five sites in the control group, but not, in the test group. The histomorphometric analysis showed similar amounts of mineralized bone in both control and test groups, 42.87+11.33% and 45.47+7.21% respectively (P>0,05). The results of 1 year clinical probing follow-up showed deeper probing depths around the control group dental implants when compared to the test group, 4.45+1.58mm and 3.78+1.58mm, respectively (P< 0,05). Radiographic analysis showed more marginal bone level loss in the control group when compared to test group, 3.44+3.39mm and 1.05+0.9mm, respectively (P<0,05). Conclusion: These findings suggest that the autologous bone marrow graft can contribute to alveolar bone repair after tooth extraction and can also minimize the dental implants attachment loss. This study indicate that the participation of mesenchymal stem cell in the alveolar bone healing should be better understanding to explain this process of repairement. Disclosures: No relevant conflicts of interest to declare.


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