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Radiation treatment plays a mainstream role in the management of head and necksquamous cell carcinomas (HNSCCs). Adverse effects from radiation therapy include osteoradionecrosis of the jaw, and rarely, pathologic fracture. Immune checkpoint inhibitors (ICI) such as pembrolizumab are of growing relevance to the management of metastatic and recurrent HNSCCs. Adverse impacts on bone secondary to medications such as pembrolizumab and nivolumab have been sporadically documented in the literature. The objective of this manuscript is to raise awareness of possible increase in risk for adverse jaw outcomes in patients with HNSCCs exposed to both radiation treatment to the jaws and ICI therapy. This manuscript documents adverse jaw outcomes including osteonecrosis and pathologic fracture of the mandible in two patients receiving pembrolizumab for management of HNSCC who had received prior radiation treatment. A potential link between immunotherapy and adverse jaw outcomes is consistent with the growing understanding of osteoimmunology, investigating the closely interrelated processes in bone remodeling and immune system function, in health and disease. It is important to ascertain if pembrolizumab poses an incremental risk for such outcomes, beyond the risk from prior radiation, for patients managed with radiation treatment and ICI therapy for HNSCC. The general dental practitioner may encoun-tersuch patients either in the context of facilitating dental clearance prior to initiation of chemotherapy, or rarely, with poorly explained jaw symptoms and must be alert to the possibility of occurrence of such adverse jaw events to facilitate timely diagnosis and optimal patient management. [ABSTRACT FROM AUTHOR]

Background: Osteonecrosis (ON) is a debilitating orthopedic condition characterized by bone cell death due to impaired blood supply, leading to structural changes and disability. Osteoporosis (OP), a systemic skeletal disease, results in reduced bone density and quality, making bones fragile and prone to fractures. Although distinct, OP and ON share several risk factors such as corticosteroid use and smoking. This study aims to investigate the causal relationships between OP, bone mineral density (BMD), and ON using a bidirectional two-sample Mendelian randomization (MR) approach. Methods: This study utilized genome-wide association study (GWAS) data for OP from the FinnGen database, and BMD data for the lumbar spine and femoral neck from the Genetic Factors for Osteoporosis (GEFOS) consortium. ON data were also obtained from the FinnGen database. All participants were of European descent. Genetic instruments were selected based on genome-wide significance, linkage disequilibrium, and strength (F-statistic). Bidirectional MR analysis was performed using inverse-variance weighted (IVW), MR-Egger regression, and weighted median methods to assess causality. Sensitivity analyses, including Cochran's Q test and MR-PRESSO, were conducted to evaluate heterogeneity and pleiotropy. Results: MR analysis demonstrated a positive causal effect of OP on ON using the IVW method, with an odds ratio (OR) of 1.223 (95% CI: 1.026–1.459, P = 0.025). The weighted median method also confirmed this result with an OR (95% CI) 1.290 (1.021–1.630), P = 0.033. No significant causal effects were found between BMD (lumbar spine and femoral neck) and ON. Furthermore, ON did not exhibit a causal effect on OP or BMD. Sensitivity analyses confirmed the robustness of the results, showing no evidence of heterogeneity or pleiotropy. Conclusion: This study provides evidence of a unidirectional causal relationship between OP and ON, suggesting that individuals with a genetic predisposition to OP have an increased risk of developing ON. These findings highlight the importance of early OP detection and management to potentially reduce ON incidence. The lack of a significant causal relationship between BMD and ON indicates that factors other than bone density, such as vascular health, may play a crucial role in ON development. Future research should explore these mechanisms further to inform clinical interventions. [ABSTRACT FROM AUTHOR]

Background: Understanding the intraosseous vascularity of the femoral head is important for preserving its structural integrity and function. Disruptions in microcirculation can lead to osteonecrosis of the femoral head (ONFH). This anatomical study aimed to quantify the regional distribution of the microvessels within the trabecular bone of the femoral head. Methods: Eleven beagles (five males, six females) were infused with intra-aortic radiopaque silicon, followed by micro-computed tomography imaging and 3D modelling using Avizo. EXAKT non-decalcified plastinated tissue histology of the proximal femur was performed and quantified using the Bioquant Osteo semi-automated histomorphometry with ImageJ. Vascular diameter, density, length density, and osteochondral parameters were calculated and compared within the subcortical and central zones of the femoral head in both sexes. Results: A well-developed intraosseous microvascular network was identified within the trabecular struts, resembling Volkmann's canals and integrating into Haversian system at the subchondral compact bone. Dense capillary networks traversed both trabecular and cortical bone to supply articular cartilage. Subcortical microvasculature was denser, with thinner diameters and shorter lengths compared to the central zone. The middle part of the femoral head displayed higher subcortical vascular density compared to superior and inferior parts. Strong positive correlations were observed between the endocortical area, tissue area, mean cortical width, bone surface and trabecular spacing. A moderate negative correlation was found between quiescent surface and cartilage density. No significant sex differences were observed in vascularity or bone metrics. Conclusion: Based on the spatial distribution of the microvasculature, the central zone serves as a conduit for primary intraosseous blood vessels, supplying the subcortical zone, including the cortex and articular cartilage. These findings establish baseline reference values for normal intraosseous microvessels and bone metrics in canine anatomy, which can be utilized for diagnosing and treating osteochondral diseases. [ABSTRACT FROM AUTHOR]

Purpose: Distinguishing between Osteonecrosis of the femoral head (ONFH) and Osteoarthritis (OA) can be subjective and vary between users with different backgrounds and expertise. This study aimed to construct and evaluate several Radiomics-based machine learning models using MRI to differentiate between those two disorders and compare their efficacies to those of medical experts. Methods: 140 MRI scans were retrospectively collected from the electronic medical records. They were split into training and testing sets in a 7:3 ratio. Handcrafted radiomics features were harvested following the careful manual segmentation of the regions of interest (ROI). After thoroughly selecting these features, various machine learning models have been constructed. The evaluation was carried out using receiver operating characteristic (ROC) curves. Then NaiveBayes (NB) was selected to establish our final Radiomics-model as it performed the best. Three users with different expertise and backgrounds diagnosed and labeled the dataset into either OA or ONFH. Their results have been compared to our Radiomics-model. Results: The amount of handcrafted radiomics features was 1197 before processing; after the final selection, only 12 key features were retained and used. User 1 had an AUC of 0.632 (95% CI 0.4801-0.7843), User 2 recorded an AUC of 0.565 (95% CI 0.4102-0.7196); while User 3 was on top with an AUC of 0.880 (95% CI 0.7753-0.9843). On the other hand, the Radiomics model attained an AUC of 0.971 (95% CI 0.9298-1.0000); showing greater efficacy than all other users. It also demonstrated a sensitivity of 0.937 and a specificity of 0.885. DCA (Decision Curve Analysis displayed that the radiomics-model had a greater clinical benefit in differentiating OA and ONFH. Conclusion: We have successfully constructed and evaluated an interpretable radiomics-based machine learning model that could distinguish between OA and ONFH. This method has the ability to aid both junior and senior medical professionals to precisely diagnose and take prompt treatment measures. [ABSTRACT FROM AUTHOR]

Objective: Although some patients may experience collapse progression while others may not in post-collapse osteonecrosis of the femoral head (ONFH) with a necrotic lesion located within the weight-bearing part of the acetabulum (Type B/C1), few studies have focused on the natural course after collapse. This study aimed to clarify the correlation between necrotic volume (NV) and necrotic depth (ND) in predicting collapse progression in patients with post-collapse ONFH Type B/C1. Materials and methods: We retrospectively reviewed 54 hips with post-collapse ONFH Type B/C1 from 52 consecutive patients who were conservatively followed up for more than 1 year. We measured the amount of femoral head collapse using biplane radiographs at each follow-up period, and produced Kaplan–Meier survival curves with collapse progression (≥ 1 mm) as the endpoint. We compared NV and ND, which were calculated as the ratio of the distance from the articular surface of the femoral head to the deepest point of a necrotic lesion to the femoral head diameter in the mid-coronal slice of T1-weighted magnetic resonance imaging (MRI). Results: We observed collapse progression in 31 hips (57.4%). The NV and ND were significantly greater in hips with collapse progression than in those without collapse progression (p = 0.0127 and 0.0047, respectively). Necrotic volume was significantly correlated with ND (rs = 0.56, p < 0.0001). Conclusion: This study suggests that necrotic depth on the mid-coronal slice of T1-weighted MRI can be a substitute for necrotic volume to predict collapse progression in ONFH Type B/C1. [ABSTRACT FROM AUTHOR]

Objectives: To determine the impact of alveolar socket surface area and number of root extractions for developing medication-related osteonecrosis of the jaw (MRONJ) in polypharmacy patients following multiple tooth extractions. Materials and methods: A retrospective sample of 40 patients was recruited, including 20 polypharmacy patients (109 tooth extractions) who developed MRONJ in at least one of the extraction sites, matched with 20 controls (100 tooth extractions). Tooth-specific alveolar socket surface areas were assessed using CBCT scans from the control group to establish reference values for alveolar socket surface areas in polypharmacy patients with MRONJ. Correlations between the number of extracted tooth roots, alveolar socket surface area, and development of MRONJ were analysed within the polypharmacy group. Results: 40% of tooth extractions in polypharmacy patients undergoing multiple extractions resulted in the development of MRONJ, with a higher prevalence observed in the mandible (44%). Among the extracted mandibular tooth roots, half were susceptible to MRONJ, and 45% of the exposed socket surface area was affected. Both jaws showed an increased risk (20%) of MRONJ following molar extraction. A strong positive correlation existed between extraction sites that developed MRONJ and both the number of mandibular tooth roots extracted (r = + 0.861; p < 0.001) and the total exposed alveolar socket surface area (r = + 0.757; p < 0.001). However, no significant correlations were observed in the upper jaw. Conclusions: This study is the first to demonstrate that both mandibular alveolar socket surface area and number of extracted tooth roots are positively related to extraction sites developing MRONJ in polypharmacy patients undergoing multiple tooth extractions. Clinical relevance: Identifying high-risk patients and implementing preventive strategies can reduce MRONJ incidence, underscoring the need for careful management of polypharmacy patients, especially those undergoing mandibular tooth extractions. [ABSTRACT FROM AUTHOR]

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Objective: This systematic review aimed to summarise the most common drugs with antiangiogenic effects associated with MRONJ, the diseases that patients can present and discuss the appropriate course of treatment. Materials and Methods: PubMed, Web of Science, Scopus and Embase were screened for case reports up to February 2024. Two independent reviewers selected the articles in a two‐step selection, screening 1.327 articles. The final sample was composed of 32 articles. Results: Most of the patients were male with a mean age of 58 years. Although the majority of patients had cancer, 20% were treated with drugs with antiangiogenic effects for other diseases. The lesions occurred mainly in the posterior mandible, with dental extraction associated in more than half of the cases. Antibiotic treatment was employed in most cases with amoxicillin and clavulanic acid, usually associated with 0.12% chlorhexidine or a 0.2% oral rinse. Bevacizumab was the medication most associated with the lesions (40%). Conclusion: The dental community needs to be aware of the new drugs that can cause MRONJ through antiangiogenic effects, given that new medications are being reported every day. [ABSTRACT FROM AUTHOR]

This study examines the biocompatibility, osteogenic potential, and effectiveness of polyether ether ketone (PEEK) composites for treating osteonecrosis, seeking to establish a theoretical basis for clinical application. A range of PEEK composite materials, including sulfonated polyether ether ketone (SPEEK), polydopamine-sulfonated polyether ether ketone (SPEEK-PDA), bone-forming peptide-poly-dopamine-sulfonated polyether ether ketone (SPEEK-PDA-BFP), and vascular endothelial growth factor-poly-dopamine-sulfonated polyether ether ketone (SPEEK-PDA-VEGF), were constructed by concentrated sulfuric acid sulfonation, polydopamine modification and grafting of bioactive factors. The experiments involved adult male New Zealand rabbits aged 24–28 weeks and weighing 2.6–4 kg. The SPEEK-PDA-BFP possesses the smallest water contact angle, indicating the highest hydrophilicity, with its surface characterized by a rich density of clustered BFP particles. The SPEEK-PDA-BFP exhibits superior adhesion, proliferation, and differentiation capabilities, along with pronounced bacteriostatic effects, which are attributed to its dense particle clusters. The SPEEK-PDA-BFP facilitates the formation of regular and dense bone trabeculae. Comparative study on treating osteonecrosis with SPEEK-PDA-VEGF and SPEEK-PDA-BFP highlighted the superior formation of mature bone trabeculae and angiogenic protein CD31 around SPEEK-PDA-VEGF. The PEEK composite materials have good biocompatibility, osteogenic activity and bone repair activity. In particular, SPEEK-PDA-VEGF composite materials have the best effect on bone repair. [ABSTRACT FROM AUTHOR]

Background: Atraumatic avascular necrosis (AVN) is a severe condition that may complicate the course of rheumatic diseases and contribute to long-term damage. However, there is a lack of evidence on this rare event in pediatric rheumatology. The aim of our study was to evaluate the occurrence of avascular necrosis in the context of rheumatologic diseases in Italy and to describe the main demographic and clinical features of AVN patients, with a particular focus on treatment background. Methods: All centres part of the Italian Society of Pediatric Rheumatology were invited to participate in a retrospective case collection of children with rheumatic diseases complicated by a pediatric-onset AVN. Demographic, clinical, laboratory and imaging data were recorded, together with outcome and treatment background, particularly steroid exposure. Population collected was further evaluated according to the different underlying rheumatologic disease and to the time of AVN onset. Results: Fourteen patients (SLE = 7; JIA = 4; others = 3) were collected from 7 centres. Females were predominantly affected (71%) with a median age at AVN diagnosis of 14.3 years. Multifocal involvement was mostly reported (93%), mainly involving femoral heads (44%) and knees (28%). All patients had a severe rheumatologic background and received systemic glucocorticoids with a median cumulative prednisone equivalent dose of 457.5 mg/kg. In all patients but one imaging showed persistence of abnormalities, despite the complete resolution of symptoms in 6 of them. Bisphosphonates were the most used therapeutic approach; orthopedic surgery was required in 2 cases. Conclusions: Despite its rarity, AVN may be a severe complication of pediatric rheumatic diseases. Active monitoring is crucial to promptly identify patients and to prevent long-term damage. Prospective large sample studies are required to better understand the impact of steroid exposure and its complex interplay with other potential contributing factors. [ABSTRACT FROM AUTHOR]

Background: The endoplasmic reticulum stress (ER stress) has been involved in various musculoskeletal disorders including non-traumatic osteonecrosis of femoral head (NT-ONFH). Objective: The current study aimed to investigate the association of glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer-binding protein homologous protein (CHOP) expressions in serum and femoral head (FH) tissues with NT-ONFH's severity. Methods: We enrolled NT-ONFH patients (n = 150) alongside healthy controls (HCs, n = 150). Meanwhile, 49 patients with femoral neck fracture (FNF) were also enrolled. Serum CHOP and GRP78 levels were determined through enzyme linked immunosorbent assay (ELISA). Local CHOP and GRP78 expressions were detected by immunohistochemistry, western blot, alongside real-time polymerase chain reaction (RT-PCR). Radiographic severity was assessed by FICAT grading system. The visual analogue scale (VAS) together with Harris hip score (HHS) were utilized to determine symptomatic severity. Results: Serum CHOP and GRP78 levels were markedly increased in NT-ONFH patients than HCs. NT-ONFH patients at FICAT stage 4 showed significant higher serum CHOP and GRP78 levels in contrast with those at stage 3. Furthermore, patients at stage 3 demonstrated higher serum CHOP and GRP78 levels than those at stage 2. There was a positive correlation observed between the serum CHOP and GRP78 levels and the severity of the FICAT stages. A total of 42 ONFH patients at FICAT stage 3, 40 patients at FICAT stage 4, and 49 FNF patients received total hip replacement (THR). The mRNA and protein levels of CHOP and GRP78 were elevated in necrotic area compared to the non-necrotic area of ONFH patients and the FH tissues of FNF patients with statistical significance. The expression levels of CHOP and GRP78 within the local tissues were significantly elevated in patients at FICAT stage 4 as opposed to those at stage 3. Besides, ROC curve analysis indicated that serum and local CHOP and GRP78 expressions may act as indicators of disease progression. The levels of CHOP and GRP78, both in serum and at the local site, were in a positive correlation with VAS scores but an inverse relationship with HHS. Conclusions: Serum and local GRP78 as well as CHOP expressions were positively linked with disease progression in NT-ONFH patients. Potential therapeutics targeting ER stress related protein may serve as a method for alleviating NT-ONFH. [ABSTRACT FROM AUTHOR]

Alcoholic osteonecrosis of the femoral head (AIONFH) is caused by long-term heavy drinking, which leads to abnormal alcohol and lipid metabolism, resulting in femoral head tissue damage, and then pathological necrosis of femoral head tissue. If not treated in time in clinical practice, it will seriously affect the quality of life of patients and even require hip replacement to treat alcoholic femoral head necrosis. This study will confirm whether M2 macrophage exosome (M2-Exo) miR-122 mediates alcohol-induced BMSCs osteogenic differentiation, ultimately leading to the inhibition of femoral head necrosis. M2 macrophages were identified by flow cytometry, and the isolated exosomes were characterized by transmission electron microscopy (TEM) and Nanoparticle Tracking Analysis (NTA). Next, miR-122 was overexpressed by transfecting miR-122 mimic, and the expression of miR-122 in M2 macrophages and their exosomes was evaluated. Subsequently, the effect of exosomal miR-122 on the osteogenic differentiation ability of BMSCs was detected, including cell proliferation, expression of osteogenic-related genes (RUNX2, BMP2, OPN, ALP), and calcium nodule formation. Finally, the therapeutic effect of M2-Exo was analyzed in a rat model of AIONFH, and bone repair and pathological damage were evaluated by Micro-CT, RT-qPCR, HE, Masson staining, and immunohistochemistry (COL I). The results showed that M2 macrophages were successfully polarized, with an average M2-Exo particle size of 156.4 nm and a concentration of 3.2E + 12 particles/mL. The expression of miR-122 in M2 macrophages is significantly higher than that in M0 macrophages, and miR-122 mimic can increase the content of miR-122 in M2-Exo. miR-122 in M2-Exo can promote osteogenic differentiation of rat bone marrow BMSCs, enhance cell viability, and increase the expression of osteogenesis-related genes. After being applied to the AIONFH rat model, the injection of M2-exo and miR-122 mimics significantly improved the repair effect of articular cartilage, alleviated pathological changes, and promoted the regeneration of bone tissue. M2-macrophage-derived exosomal miR-122 induces osteogenic differentiation of bone mesenchymal stem cells in treating AIONFH. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the femoral head (ONFH) is a prevalent orthopedic disorder characterized primarily by compromised blood supply. This vascular deficit results in cell apoptosis, trabecular bone loss, and structural collapse of the femoral head at late stage, significantly impairing joint function. While MRI is a highly effective tool for diagnosing ONFH in its early stages, challenges remain due to the limited availability and high cost of MRI, as well as the absence of routine MRI screening in asymptomatic patients.. In addition, current therapeutic strategies predominantly only relieve symptoms while disease-modifying ONFH drugs are still under investigation/development. Considering that blood supply of the femoral head plays a key role in the pathology of ONFH, angiogenic therapies have been put forward as promising treatment options. Emerging bioengineering interventions targeting angiogenesis hold promising potential for ONFH treatment. In this review, we introduce the advances in research into the pathology of ONFH and summarize novel bioengineering interventions targeting angiogenesis. This review sheds light upon new directions for future research into ONFH. [ABSTRACT FROM AUTHOR]

Background: Avascular necrosis (AVN) of the femoral head is a degenerative condition characterized by ischemic bone death, resulting in pain and impaired mobility. Core decompression, a surgical intervention, is widely performed for stage II AVN to alleviate symptoms and delay disease progression. While clinical and radiological outcomes are well-documented, the psychosocial dimensions of recovery remain underexplored. This study aims to understand the experiences of physically active patients diagnosed with stage II AVN who have undergone core decompression surgery during their follow-up period, allowing for a broader evaluation of the experiences of this patient group. Methods: This study used semi-structured interviews, in-depth follow-up questions, and thematic analysis to explore the experiences of physically active patients who underwent core decompression surgery for stage II AVN of the femoral head. The participants were assessed 1–3 years post-surgery. Conducted in the Orthopaedics and Traumatology outpatient clinic of Adana City Training and Research Hospital, the study included 31 patients who had core decompression surgery between January 2020 and January 2024, with at least one year of follow-up data. Data collection, including demographic and qualitative information, was carried out during the first week of April 2024, followed by the member-checking process in the third week. A thematic analysis checklist and COREQ guidelines were used to ensure analysis reliability. Results: The experiences of 31 patients (mean age 37.19 ± 8.21 years, 12 females, 19 males) were summarized into five main themes that emerged from the data analysis process: 'Expectations and Concerns Before Surgery,' 'Postoperative Physical Experiences,' 'The Psychological and Emotional Process,' 'Social Support and Family Relationships,' and 'Health Services and Medical Support." Twelve sub-themes emerged from the main themes. Conclusions: Core decompression offers significant benefits to patients with stage II AVN by improving mobility and reducing pain. However, psychological support, patient education, and robust social networks are essential to address the holistic needs of recovery. These findings highlight the importance of integrating patient-centered approaches into surgical care to optimize outcomes and satisfaction. Further qualitative research is needed to explore the experiences of AVN patients at different stages to inform multidisciplinary care strategies. [ABSTRACT FROM AUTHOR]

Background: Osteopenia (ON) and osteoporosis (OP) are highly prevalent among postmenopausal women and poses a challenge for early diagnosis. Therefore, identifying reliable biomarkers for early prediction using metabolomics is critically important. Methods: Initially, non-targeted metabolomics was employed to identify differential metabolites in plasma samples from cohort 1, which included healthy controls (HC, n = 23), osteonecrosis (ON, n = 36), and osteoporosis (OP, n = 37). Subsequently, we performed targeted metabolomic validation of 37 amino acids and their derivatives in plasma samples from cohort 2, consisting of healthy controls (HC, n = 10), osteonecrosis (ON, n = 10), and osteoporosis (OP, n = 10). Results: The non-targeted metabolomic analysis revealed an increase in differential metabolites with the progression of the disease, showing abnormalities in lipid and organic acid metabolism in ON and OP patients. Several substances were found to correlate positively or negatively with bone mineral density (BMD), for example, N-undecanoylglycine, sphingomyelins, and phosphatidylinositols exhibited positive correlations with BMD, while acetic acid, phenylalanine, taurine, inosine, and pyruvic acid showed negative correlations with BMD. Subsequently, targeted validation of 37 amino acids and their metabolites revealed six amino acids related to ON and OP. Conclusion: Significant metabolomic features were identified between HC and patients with ON/OP, with multiple metabolites correlating positively or negatively with BMD. Integrating both targeted and non-targeted metabolomic results suggests that lipid, organic acid, and amino acid metabolism may represent important metabolomic characteristics of patients with OP, offering new insights into the development of metabolomic applications in OP. [ABSTRACT FROM AUTHOR]

Background: No appropriate studies have been conducted that compare the biomechanical properties of different fenestration positions in deep circumflex iliac artery (DCIA)-vascularized iliac bone grafts for femoral head necrosis (ONFH) treatment. In this study, we aimed to explore the fenestration locations of DCIA-vascularized iliac grafting in ONFH treatment using FEA and clinical retrospective analysis. Methods: We simulated an iliac bone flap transplantation with a vascularized tip by finite element analysis (FEA). Patients were divided into four groups using different femur fenestration positions as follows: center-window group (C-group), superior-window group (S-group), medial-window group (M-group), and inferior-window group (I-group). In this study, we primarily observed the maximum femoral stress at different healing degrees (0, 25, 50, 75, and 100%). We retrospectively analyzed the changes in the postoperative Harris scores (HHS) and the imaging of 16 patients with iliac flaps for ONFH (11 and 5 cases in the center and other-positioned groups, respectively) at the final follow-up visit. Results: The FEA results showed that the peak von Mises stresses in the four groups at the time of complete healing were in the following order: group C (20.28 MPa) < group I (20.33 MPa) < group M (20.92 MPa) < group S (22.00 MPa). A clinical retrospective study following a comparison of the two groups found that the mean improvement in HHS was 18.00 ± 12.38 in the center-window group and 13.60 ± 25.55 in the other groups. However, no significant difference was observed in the rate of collapse (36.37 vs. 40.00%) or changes in the HHS between the two groups. Conclusion: A fenestration at the center of the femoral neck resulted in improved biomechanical gain and clinical outcomes. Trial registration: approval was granted by the Ethics Committee (II202418102). [ABSTRACT FROM AUTHOR]

Maxillofacial bone defects can have a profound impact on both facial function and aesthetics. While various biomaterial scaffolds have shown promise in addressing these challenges, regenerating bone in this region remains complex due to its irregular shape, intricate structure, and differing cellular origins compared to other bones in the human body. Moreover, the significant and variable mechanical loads placed on the maxillofacial bones add further complexity, especially in cases of difficult-to-treat medical conditions. This review provides a brief overview of medication-related osteonecrosis of the jaw (MRONJ), highlighting the medication-induced adverse reactions and the associated clinical challenges in treating this condition. The purpose of this manuscript is to emphasize the role of biotechnology and tissue engineering technologies in therapy. By using scaffold materials and biofactors in combination with autologous cells, innovative solutions are explored for the repair of damaged facial bones. The ongoing search for effective scaffolds that can address these challenges and improve in vitro bone preparation for subsequent regeneration in the maxillofacial region remains critical. The primary purpose of this review is to spotlight current research trends and novel approaches in this area. [ABSTRACT FROM AUTHOR]