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Dental implants are essential for the prosthetic rehabilitation of edentulous patients, requiring adequate bone volume and density for osseointegration and load support. The posterior region of the maxilla, commonly deficient in bone quality and quantity, represents a clinical challenge. This case series reports an analysis involving 69 dental implants in the atrophic maxilla of nine patients. The procedures adopted combined alloplastic hydroxyapatite grafting and leukocyte platelet-rich fibrin (L-PRF) applied to the alveolar ridge and maxillary sinus lift. With an average follow up of three years after the installation of the prostheses, an implant success rate of 98.5% was observed, showing integration and functional stability. The strategy of combining hydroxyapatite with L-PRF proved to be effective in increasing bone volume and promoting osseointegration. These findings indicate that the technique and biomaterials are viable for rehabilitating atrophic maxillae in the posterior region, offering long-lasting clinical results and a high success rate.

Statins have demonstrated positive results in alveolar repair after induced osteoporosis in humans and rats. This study aimed to evaluate the osteogenic potential of rosuvastatin (RSV) solution associated with collagen sponge in post-extraction rat alveoli. An experimental study was carried out at the Fluminense Federal University in 30 Wistar rats (female) randomly distributed into three experimental groups: group I—dental sockets filled with a blood clot (CS); group II—dental sockets filled with collagen sponge (EC); and group III—collagen sponge associated with RSV. Slides stained with hematoxylin and eosin (HE) were used for histomorphometric analysis to evaluate newly formed bone, connective tissue, and biomaterial in the respective groups, comparing them over different periods (7 and 42 days). The Shapiro–Wilk test was used to evaluate the same experimental period, and the Mann–Whitney test was used to compare the different periods between the groups. At 7 days, the clot group showed greater new bone formation (median 23.27; IQR 10.62–4.74) than the sponge group (median 2.25; IQR 3.42–1.53) and RSV group (median 0; IQR 0–0; p = 0.03), respectively. At 42 days, the clot group (median 63.90; IQR 7.54–3.73) showed better results regarding newly formed bone compared to the RSV group (median 26.33; IQR 4.78–2.24; p = 0.003). The present study demonstrated no advantages in the use of RSV in relation to the control group and no statistical difference between groups II and III.

A midpalatal suture contention after rapid maxillary expansion (RME) is a major orthodontic challenge. The objective of this study is to evaluate the effect of systemic simvastatin on suture bone remodeling after disjunction. For that, 15 Wistar rats were used. In 10, orthodontic appliances were installed and activated for 5 days for RME. These animals were randomly divided into two groups: control (CT, n = 5) and simvastatin (SVT, n = 5). Also, animals without intervention (HG, n = 5) were used. In the SVT and CT groups, 5 mg/kg of simvastatin and distilled water were administered by gavage, respectively, for 20 consecutive days. Then, the animals were euthanized and scanned in micro-computed tomography (µCT). The images were analyzed through pixel linear measurement at four different points (P1, P2, P3 and P4), in the intra-incisor distance (DI) and in the suture distance (SD). Microtomographic parameters, such as cortical bone area (Ct.Ar), cortical area fraction (Ct.Ar/Tt.Ar), and cortical thickness (Ct.Th), were obtained. Also, bone volume fraction (BV/TV) and empty space (EV) were extracted. Then, histological slides were prepared for descriptive and histomorphometric analysis. There was a statistically significant difference in the linear measurements, microtomographic parameters, and histomorphometric results between the experimental groups. In conclusion, simvastatin demonstrated an osteoinductive and antiresorptive effect in the palatine suture region after RME.

Bone tissue engineering seeks biomaterials that enable cell migration, angiogenesis, matrix deposition, and tissue regeneration. Blood concentrates like platelet-rich fibrin (L-PRF) offer a cost-effective source of cells and growth factors to enhance healing. The present study aimed to evaluate heated serum albumin with liquid PRF (Alb-PRF) and L-PRF clinically and biochemically after placement in dental sockets following mandibular third molar extraction. In a controlled, split-mouth study involving 10 volunteers, 20 extracted molars were treated with either Alb-PRF or L-PRF. Post-extraction, pain, trismus, infection presence, and swelling were measured. The concentrations of different analytes in the surgical sites were also examined. The data were statistically analyzed, with significance defined at p < 0.05 (t-test). No significant difference was noted between the groups for pain and trismus, but Alb-PRF showed a significant reduction in swelling on day seven. The Alb-PRF group showed lower levels of pro-inflammatory cytokines (GM-CSF, IL-1b, IL-6, IFNy, IL-8, IL-15, RANTES, and MIP-1a) after seven days, with only higher expressions of MIP-1b, IL-1b, and MCP-1 found in the L-PRF group. Differences were observed in the release of analytes between L-PRF and Alb-PRF, with Alb-PRF significantly reducing edema after seven days. Alb-PRF reduced edema, while L-PRF increased inflammatory cytokines. When compared to L-PRF, Alb-PRF reduced edema and the release of inflammatory cytokines, suggesting promising effects in socket healing while underscoring the role of growth factors and cytokines in potential applications of blood concentrates.

Background and objectives: Although it is very uncommon, medication-induced osteonecrosis of the jaw (also known as MRONJ) can have serious consequences. Traditionally, this adverse event has been recognised in patients who were treated with bisphosphonate (BP) drugs. Nevertheless, in recent years, it has been established that individuals having treatment with various types of medications, such as a receptor activator of nuclear factor kappa-Β ligand inhibitor (denosumab) and antiangiogenic agents, have had the same issue. The purpose of this research is to determine if the application of human amniotic membrane (hAM) may be used as a therapy for MRONJ. Material and Methods: A multi-source database (MEDLINE, EMBASE, AMED, and CENTRAL) systematic search was performed. The major objective of this study is to obtain an understanding of the efficacy of hAM when it is employed as a treatment modality for MRONJ. The protocol of this review was registered in the INPLASY register under the number NPLASY202330010. Results: The authors were able to include a total of five studies for the quality analysis, whereas for the quantity evaluation, only four studies were eligible. A total of 91 patients were considered for the investigation. After treatment with human amniotic membrane (hAM), a recurrence of osteonecrosis was observed in n = 6 cases (8.8%). The combined efficacy of surgical therapy and the use of hAM resulted in an overall success rate of 91.2%. Intraoperative complications were only documented in one article, and they were mostly caused by the positioning of the hAM, which led to wound breakdown at the surgical site. Conclusions: Based on the small amount of data and low-quality research included in this study, using human amniotic membranes to treat MRONJ might represent a feasible option. Nevertheless, further studies with a wider patient population are required to understand the long-term impacts.

Background: Antiresorptive and antiangiogenic medications can cause a serious adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). In recent years, a new trend of research has emerged emphasizing the potential relation of MRONJ and genetic predisposition. Current evidence-based science of this adverse reaction is associated with poorly performed studies. Additionally, MRONJ research has recently observed a new trend of studies orientated towards the misuse of reviews. This quality meta-review intends to summarize the results of all systematic reviews and meta-analyses that have been published on MRONJ in relation to genetic and pharmacogenomics risk factors. Methods: The research study protocol was registered into the database of the International Network for the Registration of Systematic Reviews and Meta-Analyses (INPLASY) INPLASY202230002. A comprehensive search across several databases (PubMed, EMBASE, MEDLINE, and CINAHL) was conducted to locate multi-language papers published between January 2003 and November 2022. Data were collected from relevant research studies and appraised in accordance with the precise outcomes described in this evaluation. Results: Only five systematic reviews and meta-analyses were analysed in this meta-review. All the reviews included in this research presented qualities mistakes and shortcomings. Two quality assessment tools (Confidence in Evidence from Reviews of Qualitative research (CERQual) and Assessment of Multiple Systematic Reviews 2 (AMSTAR-2)) were used to evaluate each study included in this research. Conclusions: The data evaluated by this meta-review confirmed the poor-quality secondary research underpinning the genetic/pharmacogenomics aspect of MRONJ. Moreover, this study highlighted the many flaws of the current published systematic and meta-analysis studies published so far.

Medication-related osteonecrosis of the jaw (MRONJ) is considered as a severe adverse side effect of specific drugs such as anti-resorptive and anti-angiogenic medications. Evidence suggests that MRONJ is linked to invasive dental procedures, mainly dentoalveolar surgery. Several preventive strategies to minimize the risk of developing MRONJ have been investigated. However, no investigation has been attempted to evaluate the therapeutic effect of local drug-delivery technology as a preventive strategy protocol. The aim of this study is to evaluate the efficacy of hydroxyapatite-containing doxycycline (HADOX) in rats with high-risk MRONJ development. All the rats used in this study were divided into seven groups. Six groups of rats out of seven were exposed to two different doses of antiresorptive drug therapy for four weeks before undergoing an upper incisor extraction. After 28 days, all the animals were euthanized, and the bone blocks were processed for histological and histomorphometrical evaluation. The histomorphometric analysis confirmed that newly formed bone (NFB) was present in all groups, with significant differences. NFB in the HADOX group treated with zoledronic acid at 4% showed (28.38; C.I. 22.29–34.48), which represents a significant increase compared to HA (15.69; C.I. 4.89–26.48) (p = 0.02). A similar pattern was observed in the HADOX group treated with zoledronic acid 8% ZA treatment (p = 0.001). Conclusions: HADOX did not inhibit any bone repair and reduced early inflammatory response. Hence, HADOX could promote bone healing in patients undergoing antiresorptive drug therapy.

Background: The degree of biodegradation and the inflammatory response of membranes employed for guided bone regeneration directly impact the outcome of this technique. This study aimed to evaluate four different experimental versions of Poly (L-lactate-co-Trimethylene Carbonate) (PTMC) + Poly (L-lactate-co-glycolate) (PLGA) membranes, implanted in mouse subcutaneous tissue, compared to a commercially available membrane and a Sham group. Methods: Sixty Balb-C mice were randomly divided into six experimental groups and subdivided into 1, 3, 6 and 12 weeks (n = 5 groups/period). The membranes (1 cm2) were implanted in the subcutaneous back tissue of the animals. The samples were obtained for descriptive and semiquantitative histological evaluation (ISO 10993-6). Results: G1 and G4 allowed tissue adhesion and the permeation of inflammatory cells over time and showed greater phagocytic activity and permeability. G2 and G3 detached from the tissue in one and three weeks; however, in the more extended periods, they presented a rectilinear and homogeneous aspect and were not absorbed. G2 had a major inflammatory reaction. G5 was almost completely absorbed after 12 weeks. Conclusions: The membranes are considered biocompatible. G5 showed a higher degree of biosorption, followed by G1 and G4. G2 and G3 are considered non-absorbable in the studied periods.

Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is rare. It is a serious adverse effect of certain drugs, of which bisphosphonates (BPs) are the most widely known. The aim of this systematic review was to analyze all published evidence for the reported adverse outcomes as a result of orthodontic treatment in patients undergoing antiresorptive therapy. Data: All types of studies involving patients undergoing orthodontic treatment and treated with antiresorptive drugs were considered. A meta-analysis was not conducted due to the high amount of variability and heterogeneity in the reporting and presentation of data among the studies meeting the inclusion criteria. Sources: A systematic search was performed using 4 databases (PubMed, MEDLINE, EMBASE and CINAHL). Study selection: Seven studies matched the inclusion criteria for this review, reporting a total of 29 patients. MRONJ was only reported in 1 patient. The adverse outcomes following orthodontic treatment included difficulty achieving root parallelism (n = 4), difficulty achieving complete space closure (n = 3), exaggerated tooth mobility post-debond (n = 2), increased duration of orthodontic treatment beyond expected completion (n = 1), sclerotic alveolar bone changes seen on post-op radiographic images (n = 2), and an increased amount of root resorption (n = 1). Conclusions: The high amount of heterogeneity and limited evidence precluded a valid interpretation and analysis of the results through pooling of data. Additional data with sufficient quality, a reduction of bias, and a greater prospective cohort of patients is crucial to assess adverse effects, mechanisms of action, and associated risk factors in at-risk patients. Clinical significance: Based on the limited evidence available in the literature, it is unclear whether orthodontic treatment alone can precipitate MRONJ. However, antiresorptive drug therapy may be associated with a sub-optimal treatment outcome.

Background: Osteonecrosis of the jaw (ONJ) is a condition affecting patients exposed to medications used to treat benign and malignant conditions of bone tissue. Many studies have highlighted that ONJ is a severe condition, which is very challenging to manage, especially in individuals with oncologic disease. The aim of this umbrella review is to analyze all available interventional and non-interventional systematic reviews published on medication-related osteonecrosis of the jaw (MRONJ) and summarize this evidence. Material and methods: A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until June 2021. An additional manual search was also performed in systematic review registries (PROSPERO, INPLASY, JBI and OFS) to identify possible missing reviews. Data were extracted from relevant papers and analyzed according to the outcomes selected in this review. Results: The search generated 25 systematic reviews eligible for the analysis. The total number of patients included in the analysis was 80,840. Of the reviews, 64% (n = 16) were non-interventional and 36% (n = 9) were interventional. Study designs included case series 20.50% (n = 140), retrospective cohort studies 12.30% (n = 84) and case reports 12.20% (n = 83). It was unclear what study design was used for 277 studies included in the 25 systematic reviews. Conclusions: The data reviewed confirmed that the knowledge underpinning MRONJ in the last 20 years is still based on weak evidence. This umbrella review highlighted a widespread low-level quality of studies and many poorly designed reviews.

Medication related osteonecrosis of the jaw (MRONJ) is a severe condition affecting the jaws of patients exposed to specific drugs, and is primarily described in patients receiving bisphosphonate (BP) therapy. However, more recently it has been observed in patients taking other medications, such as the RANK ligand inhibitor (denosumab) and antiangiogenic drugs. It has been proposed that the existence of other concomitant medical conditions may increase the incidence of MRONJ. The primary aim of this research was to analyze all available evidence and evaluate the reported outcomes of osteonecrosis of the jaws (ONJ) due to antiresorptive drugs in immunosuppressed patients. A multi-database (PubMed, MEDLINE, EMBASE and CINAHL) systematic search was performed. The search generated twenty-seven studies eligible for the analysis. The total number of patients included in the analysis was two hundred and six. All patients were deemed to have some form of immunosuppression, with some patients having more than one disorder contributing to their immunosuppression. Within this cohort the commonest trigger for MRONJ was a dental extraction (n=197). MRONJ complications and recurrence after treatment was sparsely reported in the literature, however a total of fourteen cases were observed. The data reviewed have confirmed that an invasive procedure is the commonest trigger of MRONJ with relatively high frequency of post-operative complications or recurrence following management. However, due to low-quality research available in the literature it is difficult to draw a definitive conclusion on the outcomes analysed in this systematic review.

Many biomaterials are used for Bone Morphogenetic Proteins (BMPs) delivery in bone tissue engineering. The BMP carrier system’s primary function is to hold these growth factors at the wound’s site for a prolonged time and provide initial support for cells to attach and elaborate the extracellular matrix for bone regeneration. This study aimed to evaluate the nanostructured carbonated hydroxyapatite microspheres (nCHA) as an rhBMP-2 carrier on rats calvaria. A total of fifteen male Wistar rats were randomly divided into three groups (n = 5): clot (control group), rhBMP-2 associated with collagen membrane (COL/rhBMP-2) or associated with the microspheres (nCHA/rhBMP-2). After 45 days, the calvaria defect samples were evaluated through histological, histomorphometric, and SR-µCT analyses to investigate new-formed bone and connective tissue volume densities. The descriptive histological analysis showed that nCHA/rhBMP-2 improved bone formation compared to other groups. These results were confirmed by histomorphometric and SR-µCT analysis that showed substantially defect area filling with a higher percentage of newly formed (36.24 ± 6.68) bone than those with the COL/rhBMP-2 (0.42 ± 0.40) and Clot (3.84 ± 4.57) (p < 0.05). The results showed that nCHA is an effective carrier for rhBMP-2 encouraging bone healing and an efficient alternative to collagen membrane for rhBMP-2 delivery.

This overview aimed to evaluate the methods, quality, and outcomes of systematic reviews (SRs) conducted to investigate the effects of platelet-rich fibrin (PRF) in dental sockets on promoting bone regeneration and soft tissue healing and diminishing the incidence of pain, swelling, trismus, and alveolar osteitis after tooth extraction. An electronic search without date or language restriction was done in PubMed/MEDLINE, Cochrane, and Web of Science until March 2020. Eligibility criteria included SRs that assessed the effect of PRF for human alveolar socket preservation. The quality assessment of the included studies was performed using AMSTAR 2 guidelines. The protocol of this overview was recorded in PROSPERO under the number CRD42018089617. The search and selection process yielded 13 studies published between 2011 and 2018. The analysis of the studies showed inconclusive data for the effect of the PRF and the dimensional changes. There is no definitive evidence for the impact of using PRF alone on bone regeneration in post-extraction sockets. The use of PRF improves soft tissue healing and reduces pain, bleeding, and osteitis in post-extraction sockets.

ABSTRACT Objective: This study aimed to evaluate bone repair in rat dental sockets after implanting nanostructured carbonated hydroxyapatite/sodium alginate (CHA) and nanostructured carbonated hydroxyapatite/sodium alginate containing 5% strontium microspheres (SrCHA) as bone substitute materials. Methods: Twenty male Wistar rats were randomly divided into two experimental groups: CHA and SrCHA (n=5/period/group). After one and 6 weeks of extraction of the right maxillary central incisor and biomaterial implantation, 5 μm bone blocks were obtained for histomorphometric evaluation. The parameters evaluated were remaining biomaterial, loose connective tissue and newly formed bone in a standard area. Statistical analysis was performed by Mann-Withney and and Wilcoxon tests at 95% level of significance. Results: The histomorphometric results showed that the microspheres showed similar fragmentation and bio-absorbation (p>0.05). We observed the formation of new bones in both groups during the same experimental periods; however, the new bone formation differed significantly between the weeks 1 and 6 (p=0.0039) in both groups. Conclusion: The CHA and SrCHA biomaterials were biocompatible, osteoconductive and bioabsorbable, indicating their great potential for clinical use as bone substitutes.