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Purpose: To evaluate the stability of interdental papilla filling using hyaluronic acid (HA) to treat black triangles in esthetic regions., Methods: The protocol was registered in PROSPERO. Six databases (PubMed, Scopus, Embase, Lilacs, SciELO, and Web of Science) were used as primary search sources, and OpenGrey and OpenThesis were used to capture the "gray literature." Only before-after studies were included. The JBI Checklist assessed the risk of bias. Only four studies met the inclusion criteria and were considered for the analyses. The studies were published from 2010 to 2016. All studies presented a low risk of bias. Considering the studies do not have control groups, a weighted average by sample size was calculated to obtain a general estimate of the percentage of papillary filling after 6 months and the number of HA applications., Results: The studies showed the percentage of papillary reconstruction after 6 months of application, the weighted average by sample size was 77.41% (SD = 20.68), with an average number of applications of 3.17 (SD = 0.31)., Conclusion: The application of HA may be used to repair anesthetic defects in the papilla., Clinical Significance: Interdental papilla reconstruction with injectable HA is an option of nonsurgical treatment for interdental papilla deficiencies. However, there is still concern about the quality of the evidence available, considering that studies with different experimental designs can produce contradictory results. Moreover, further understanding is required on the stability of tissue gain promoted by HA in black triangles., (© 2020 Wiley Periodicals LLC.)

Objective: The aim of this study was to investigate the effects of the long-term alendronate administration on bone healing in defects created in rat calvarias., Materials and Methods: Female Wistar rats were randomly distributed into 2 groups: Control (CTL): animals received saline solution once a week; and Alendronate (ALD): rats underwent alendronate treatment (1 mg/kg/weekly). After 120 days from the commencement of treatment, a critical size defect was created in all animals, and 10 animals from each group were sacrificed at 5, 10, 15, 20, 25, 30, 45 and 60-days after the defect creation. On the day of sacrifice, urine and blood samples were collected for determination of the serum levels of bone resorption and formation markers by enzyme linked immunosorbent assay, and the urinary concentration of deoxypyridinoline. Bone mineral density (BMD) in the femurs, descriptive histology, tartrate-resistant acid-phosphatase staining and immunohistochemical analyzes were assessed in the calvaria., Results: Alendronate group showed increased BMD compared to the test group. The concentration of C-terminal telopeptide of type I collagen and deoxypyridinoline decreased significantly, and the concentration of aminoterminal propeptide of procollagen type 1 and osteocalcin were significant lower in the alendronate group. Immunohistochemical analysis showed significant downregulation in the inducible nitric oxide synthase, runt-related transcription factor-2, cathepsin-K and receptor activator of nuclear factor kappa-B ligand expression in the alendronate group. Vascular endothelial growth factor and osteopontin were upregulated in the later periods of alendronate group., Conclusions: Our results suggest that long-term treatment with alendronate did not compromise the repair processing of critical size defects in rat., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to assess the volumetric stability and bone formation in grafts with Bio-Oss and autogenous bone at different proportions in rabbit calvaria. Material and Methods . Ten rabbits received four titanium cylinders in their calvaria and randomly divided into the following groups: Group I: Bio-Oss (100%), Group II: Bio-Oss (75%) + autogenous bone (25%), Group III: Bio-Oss (50%) + autogenous bone (50%), and Group IV: autogenous bone (100%). After twelve weeks, the animals were euthanized, and samples were collected for clinical and histological analysis., Results: Clinical analysis showed that Groups I (90.43 ± 8.99) and II (90.87 ± 7.43) had greater dimensional stability compared to Group IV ( P =0.0005). Histologically, Groups I, II, and III showed areas of bone formation with particles of biomaterial remaining in close contact with the newly formed bone. However, there were no significant differences between the groups regarding the newly formed bone area., Conclusion: It was concluded that the use of Bio-Oss either alone or associated with the autogenous bone at a proportion of 25% showed superior dimensional stability compared to the use of autogenous bone in the proposed experimental model., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Yeon Jung Kim et al.)

Considering the higher number of bisphosphonate prescriptions worldwide and the risk of medicine-related osteonecrosis of the jaws (MRONJs) associated with these drugs, this study aims to report a patient who had weekly used sodium alendronate for 7 years and was submitted to an implant-supported rehabilitation. The alendronate intake was interrupted by the physician 1 year prior to the beginning of the procedures until the whole dental treatment was finished. Moreover, the bone markers procollagen type 1 N-terminal propeptide and C-terminal cross-linking telopeptide of type 1 collagen were also evaluated and showed the following values, respectively: 150 pg/mg and 27.3 μg/L. The rehabilitation consisted of a careful extraction of teeth 34 and 48, external hexagon implants placement at 34, 36, 37, 46, and 47 sites and cone morse at 41 tooth region. During implants insertion, portions of the bone were collected. It was also performed, a gingival graft at 41 region. After 4 months, it was installed the provisional crowns and 1 year later, the definitive ones. It was observed success of the dental rehabilitation, without any clinical or radiographic signs of MRONJ. Moreover, mandibular bone showed normality aspects, with several osteocytes. Although, alendronate use was restarted after the rehabilitation had been finished, the 2-year follow-up has proved the success of the treatment. Based on these findings, it is possible to consider that the clinical protocol ensured the success of the dental rehabilitation, even with the long-term use of a bisphosphonate.

This study was performed to investigate sinus floor augmentation with two different particle sizes of demineralized bovine bone mineral (DBBM) by means of histological and immunohistochemical (IHC) analysis. A randomized clinical trial was conducted involving 10 individuals requiring two-stage bilateral maxillary sinus augmentation for implant installation. The patients were randomly divided into two groups following a split-mouth design: the maxillary sinus on one side was filled with small-sized particles (0.25-1mm) and on the contralateral side with large-sized particles (1-2mm). After a healing period of 8 months, 25 implants were placed. During implant site preparation, bone biopsies were obtained from each sinus, perpendicular to the long axis of the implant (buccal-palatal direction), for descriptive and histomorphometric analyses. IHC staining for protein expression of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and tartrate-resistant acid phosphatase (TRAP) was also performed. Histomorphometric analysis revealed no statistically significant difference in the percentage of biomaterial (32.4±8.56% and 38.0±6.92%), newly formed bone (36.1±9.60% and 36.7±5.79%), or connective tissue (30.4±8.63% and 23.8±6.16%) between the small- and large-sized particle groups, respectively. IHC analysis did not reveal differences in the expression of OCN, VEGF, or TRAP. These findings suggest that both particle sizes of DBBM are effective for bone augmentation in the maxillary sinus., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Purpose: The objective of this investigation was to assess vertical bone augmentation using deproteinized bovine bone mineral (DBBM) infused or not with recombinant human bone morphogenetic protein (rhBMP-2) in rabbit tibiae., Materials and Methods: A total of 18 female rabbits (New Zealand) received two blocks of DBBM in each tibia. The DBBM blocks were randomly assigned into four experimental groups: DBBM (only the bone graft); DBBM associated with absorbable collagen sponge (ACS); DBBM plus rhBMP-2 (1.5 mg/mL); and DBBM infused with rhBMP-2 (1.5 mg/mL) in an ACS carrier. Animals were sacrificed after 12 weeks, and the tibiae containing the DBBM blocks were dissected and analyzed radiographically (microcomputed tomography [micro-CT]), histologically, and immunohistochemically., Results: Micro-CT analysis showed a considerable increase in bone volume (BV) and BV/tissue volume in the rhBMP-2/ACS group compared with all the others. Trabeculae thickness also increased in the rhBMP-2/ACS group compared with the DBBM/ACS group. Trabecular number, separation, and bone mineral density were not different among groups. Histomorphometric evaluation showed increased newly formed bone in the rhBMP-2/ACS group compared with the DBBM and DBBM/ACS groups. The amount of residual bone graft was statistically higher in the rhBMP-2 groups compared with the DBBM/ACS group. Immunohistochemical analysis showed that the vascular endothelial growth factor (VEGF) expression was more intense in the rhBMP-2/ACS group compared with the DBBM/ACS group. The immunopositivity for type 1 collagen tended to be higher in the two groups with rhBMP-2., Conclusion: Collectively, the results of this study suggest that the addition of rhBMP-2 in an ACS carrier placed on top of the DBBM graft enhanced bone formation in this animal model.

Aim: The aim of this nonrandomized controlled preliminary clinical trial was to compare treatment using short and conventional implants in the posterior region of the mandible after prosthesis installation by means of clinical, resonance frequency, and radiographic analyses., Materials and Methods: A total of 10 patients with 40 dental implants already installed were included in this study. Four implants were installed for each subject, in which the length of the implants (short and conventional) was distributed according to the reminiscent alveolar bone in the left and right side of the mandible. All implants received splinted prosthesis after the osseointegration period. Analyses were performed immediately after prosthesis installation (T1), and 3 (T2) and 6 months (T3) after prosthesis placement., Results: The 6-month survival and success rates were 100% for the short and conventional implants. Probing depths (PDs) after 6 months did not show statistical differences between short and conventional implants. All groups showed mean implant stability quotient (ISQ) values above 60 in all periods evaluated, demonstrating great implant stability, and no differences were found between groups at T3. Radiographic measurements showed an increased bone loss for conventional implants compared with short implants in all the three periods evaluated., Conclusion: Our findings suggest that treatment of resorbed posterior regions in the mandible with shorter dental implants is as reliable as treatment with conventional implants after 6 months of splinted prosthesis installation., Clinical Significance: Short implants might be considered a predictable treatment alternative to bone augmentation or extensive surgical techniques in regions of restricted vertical bone height in the posterior region of the mandible.

Purpose: We sought to evaluate the effectiveness of bone substitutes in circumferential peri-implant defects created in the rabbit tibia., Methods: Thirty rabbits received 45 implants in their left and right tibia. A circumferential bone defect (6.1 mm in diameter/4 mm depth) was created in each rabbit tibia using a trephine bur. A dental implant (4.1 mm × 8.5 mm) was installed after the creation of the defect, providing a 2-mm gap. The bone defect gaps between the implant and the bone were randomly filled according to the following groups: blood clot (CO), particulate Bio-Oss(®) (BI), and Bio-Oss(®) Collagen (BC). Ten animals were euthanized after periods of 15, 30, and 60 days. Biomechanical analysis by means of the removal torque of the implants, as well as histologic and immunohistochemical analyses for protein expression of osteocalcin (OC), Runx2, OPG, RANKL, and TRAP were evaluated., Results: For biomechanics, BC showed a better biological response (61.00±15.28 Ncm) than CO (31.60±14.38 Ncm) at 30 days. Immunohistochemical analysis showed significantly different OC expression in CO and BC at 15 days, and also between the CO and BI groups, and between the CO and BC groups at 60 days. After 15 days, Runx2 expression was significantly different in the BI group compared to the CO and BC groups. RANKL expression was significantly different in the BI and CO groups and between the BI and BC groups at 15 days, and also between the BI and CO groups at 60 days. OPG expression was significantly higher at 60 days postoperatively in the BI group than the CO group., Conclusions: Collectively, our data indicate that, compared to CO and BI, BC offered better bone healing, which was characterized by greater RUNX2, OC, and OPG immunolabeling, and required greater reversal torque for implant removal. Indeed, along with BI, BC presents promising biomechanical and biological properties supporting its possible use in osteoconductive grafts for filling peri-implant gaps.

Background: The erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser has been widely used in the dental clinic; however, few studies have demonstrated the advantages of the use of this laser for bone osteotomies. The purpose of this study is to evaluate and compare the bone repair process of defects generated by the Er,Cr:YSGG laser or conventional drills., Methods: Ninety-six rats were divided into two groups of 48 animals (drill group and laser group). After surgical exposure of the right tibia, the animals were subjected to a 2-mm-diameter osteotomy created by conventional drills (drill group) or by the Er,Cr:YSGG laser (laser group). The animals were sacrificed 0, 3, 7, 14, 30, and 60 days after the creation of the defect, and histologic sections were obtained and used for histomorphometric and immunohistochemical analyses for the detection of osteocalcin, osteoprotegerin, receptor activator of nuclear factor κ-B ligand, vascular endothelial growth factor, and caspase-3., Results: The osteotomy with the drill produced well-delimited and smooth walls, whereas the osteotomies in the laser group were irregular and presented an amorphous basophilic line and bone necrosis that was slowly resorbed during the repair process. Despite these characteristics, bone repair was similar between groups at various time points, and, at 60 days, the defects in both groups were completely repaired by newly formed bone., Conclusion: The repair process of osteotomies created by the Er,Cr:YSGG laser, despite producing thermal damage to bone tissue, is comparable to that with conventional drills.

Objective: Short implants are increasingly used, but there is doubt about their performance being similar to that of regular implants. The aim of this study was to compare the mechanical stability of short implants vs. regular implants placed in the edentulous posterior mandible., Material and Methods: Twenty-three patients received a total of 48 short implants (5 × 5.5 mm and 5 × 7 mm) and 42 regular implants (4 × 10 mm and 4 × 11.5 mm) in the posterior mandible. Patients who received short implants had <10 mm of bone height measured from the bone crest to the outer wall of the mandibular canal. Resonance frequency analysis (RFA) was performed at time intervals T0 (immediately after implant placement), T1 (after 15 days), T2 (after 30 days), T3 (after 60 days), and T4 (after 90 days)., Results: The survival rate after 90 days was 87.5% for the short implants and 100% for regular implants (P < 0.05). There was no significant difference between the implants in time intervals T1, T2, T3, and T4. In T0, the RFA values of 5 × 5.5 implants were higher than values of 5 × 7 and 4 × 11.5 implants (P < 0.05). A total of six short implants that were placed in four patients were lost (three of 5 × 5.5 mm and three of 5 × 7 mm). Three lost implants started with high ISQ values, which progressively decreased. The other three lost implants started with a slightly lower ISQ value, which rose and then began to fall., Conclusions: Survival rate of short implants after 90 days was lower than that of regular implants. However, short implants may be considered a reasonable alternative for rehabilitation of severely resorbed mandibles with reduced height, to avoid performing bone reconstruction before implant placement. Patients need to be aware of the reduced survival rate compared with regular implants before implant placement to avoid disappointments., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Piezosurgery is an osteotomy system used in medical and dental surgery. Many studies have proven clinical advantages of piezosurgery in terms of quality of cut, maneuverability, ease of use, and safety. However, few investigations have tested its superiority over the traditional osteotomy systems in terms of dynamics of bone healing. Therefore, the aim of this study was to evaluate the dynamics of bone healing after osteotomies with piezosurgery and to compare them with those associated to traditional bone drilling., Methods: One hundred and ten rats were divided into two groups with 55 animals each. The animals were anesthetized and the tibiae were surgically exposed to create defects 2 mm in diameter by using piezosurgery (Piezo group) and conventional drilling (Drill group). Animals were sacrificed at 3, 7, 14, 30 and 60 days post-surgery. Bone samples were collected and processed for histological, histomorphometrical, immunohistochemical, and molecular analysis. The histological analysis was performed at all time points (n = 8) whereas the histomorphometrical analysis was performed at 7, 14, 30 and 60 days post-surgery (n = 8). The immunolabeling was performed to detect Vascular Endothelial Growth Factor (VEGF), Caspase-3 (CAS-3), Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), and Osteocalcin (OC) at 3, 7, and 14 days (n = 3). For the molecular analysis, animals were sacrificed at 3, 7 and 14 days, total RNA was collected, and quantification of the expression of 21 genes related to BMP signaling, Wnt signaling, inflammation, osteogenenic and apoptotic pathways was performed by qRT-PCR (n = 5)., Results: Histologically and histomorphometrically, bone healing was similar in both groups with the exception of a slightly higher amount of newly formed bone observed at 30 days after piezosurgery (p < 0.05). Immunohistochemical and qRT-PCR analyses didn't detect significant differences in expression of all the proteins and most of the genes tested., Conclusions: Based on the results of our study we conclude that in a rat tibial bone defect model the bone healing dynamics after piezosurgery are comparable to those observed with conventional drilling.

Purpose: To evaluate the effect of implant osteotomy on immediate bone cell viability, comparing guided surgery for implant placement with the classic drilling procedure., Materials and Methods: For this study, 20 rabbits were used. The animals were divided into a guided surgery group (GG) and a control group (CG) and were then divided into 4 subgroups--subgroups 1, 2, 3, and 4--corresponding to drills used 10, 20, 30, and 40 times, respectively. All animals received 5 osteotomies in each tibia, by use of the classic drilling procedure in one tibia and guided surgery in the other tibia. The osteotomized areas were removed and processed immunohistochemically for detection of osteocalcin, receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and caspase 3., Results: Immunohistochemical analysis showed that osteocalcin expression was initially higher in the CG and remained constant after drill reutilization. Although the expressions of RANKL and OPG were not statistically different for the GG and CG, the RANKL/OPG ratio tended to be higher for the GG. Moreover, caspase 3 expression was elevated in the GG, proportionally to the number of osteotomies, indicating an increase in the apoptosis index in the GG., Conclusions: The classic drilling procedure is more favorable to cell viability than guided surgery., (Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

It has been demonstrated that histamine interferes with the recruitment, formation and activity of osteoclasts via H(1)- and H(2)-receptors. Cimetidine is a H(2)-receptor antagonist used for treatment of gastric ulcers that seems to prevent bone resorption. In this study, a possible cimetidine interference was investigated in the number of alveolar bone osteoclasts. The incidence of osteoclast apoptosis and immunoexpression of RANKL (receptor activator of nuclear factor κB ligand) was also evaluated. Adult male rats were treated with 100 mg kg(-1) of cimetidine for 50 days (CimG); the sham group (SG) received saline. Maxillary fragments containing the first molars and alveolar bone were fixed, decalcified and embedded in paraffin. The sections were stained by H&E or submitted to tartrate-resistant acid phosphatase (TRAP) method. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) method and immunohistochemical reactions for detecting caspase-3 and RANKL were performed. The number of TRAP-positive osteoclasts, the frequency of apoptotic osteoclasts and the numerical density of RANKL-positive cells were obtained. Osteoclast death by apoptosis was confirmed by transmission electron microscopy (TEM). In CimG, TRAP-positive osteoclasts with TUNEL-positive nuclei and caspase-3-immunolabeled osteoclasts were found. A significant reduction in the number of TRAP-positive osteoclasts and a high frequency of apoptotic osteoclasts were observed in CimG. Under TEM, detached osteoclasts from the bone surface showed typical features of apoptosis. Moreover, a significant reduction in the numerical density of RANKL-positive cells was observed in CimG. The significant reduction in the number of osteoclasts may be due to cimetidine-induced osteoclast apoptosis. However, RANKL immunoexpression reduction also suggests a possible interference of cimetidine treatment in the osteoclastogenesis., (© 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.)

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is not completely understood and difficult to treat. Even though the occurrence of BRONJ is mainly related to the therapy with intravenous bisphosphonates (BPs), this article reports a case of long-term oral BP use and BRONJ occurrence. In addition, a literature review provides some additional information about BPs, BRONJ, and also a guideline for the prevention and treatment of BRONJ stages. A 79-year-old patient presented intense and persistent pain, purulent secretion, and exposed bone at the right side of the lower jaw. Thus, she was submitted to anamnesis, radiologic and tomographic examinations, and bacterial culture and sensitivity tests. These procedures were followed by surgical debridement of the bone and surrounding tissues/cyst and antibiotic prescription and histopathologic analysis of the fragments. Together, the examinations performed showed the occurrence of stage 2 BRONJ. Moreover, the antibiotic prescription, discontinuation of oral BP, and surgical procedures ensure that the patient had no more symptoms. Therefore, considering the presented case, we believe that an accurate approach is promising to diagnose and treat stage 2 BRONJ and other associated pathologic findings.

Increasing evidence suggests the existence of osteoclast diversity. Here we investigated whether precursors obtained from marrow of the mandibula or long bone could give rise to phenotypically different osteoclasts. Formation of multinucleated cells was assessed after culturing mouse marrow cells of the two bone types with macrophage colony stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL) for up to 10days on plastic, bone or dentin. Two times more osteoclasts formed from long bone marrow cells on bone compared to dentin, whereas higher numbers of jaw osteoclasts formed on dentin. Resorption of dentin or bone was similar for osteoclasts formed from both types of precursors. In contrast to jaw marrow derived osteoclasts, long bone osteoclasts predominantly had a multi-compartmented shape, with at least two nuclei containing compartments per cell. Osteoclasts on bone contained two times more actin rings than osteoclasts on dentin, regardless of their precursor origin. However, the area per osteoclast covered by actin rings was similar (20%) for both substrates. This study suggests that marrow cells obtained from different bones give rise to different osteoclasts. The substrate on which the osteoclasts are generated plays a role in steering their formation rather than their resorption., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Osteoclasts, the multinucleated bone-resorbing cells, arise through fusion of precursors from the myeloid lineage. However, not all osteoclasts are alike; osteoclasts at different bone sites appear to differ in numerous respects. We investigated whether bone marrow cells obtained from jaw and long bone differed in their osteoclastogenic potential. Bone marrow cells from murine mandible and tibiae were isolated and cultured for 4 and 6 days on plastic or 6 and 10 days on dentin. Osteoclastogenesis was assessed by counting the number of TRAP(+) multinucleated cells. Bone marrow cell composition was analyzed by FACS. The expression of osteoclast- and osteoclastogenesis-related genes was studied by qPCR. TRAP activity and resorptive activity of osteoclasts were measured by absorbance and morphometric analyses, respectively. At day 4 more osteoclasts were formed in long bone cultures than in jaw cultures. At day 6 the difference in number was no longer observed. The jaw cultures, however, contained more large osteoclasts on plastic and on dentin. Long bone marrow contained more osteoclast precursors, in particular the myeloid blasts, and qPCR revealed that the RANKL:OPG ratio was higher in long bone cultures. TRAP expression was higher for the long bone cultures on dentin. Although jaw osteoclasts were larger than long bone osteoclasts, no differences were found between their resorptive activities. In conclusion, bone marrow cells from different skeletal locations (jaw and long bone) have different dynamics of osteoclastogenesis. We propose that this is primarily due to differences in the cellular composition of the bone site-specific marrow.