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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]

Objective: Patients taking antiresorptive medications in dental clinics are at risk of medication-related osteonecrosis of the jaw (MRONJ), which poses daily challenges for their clinicians. This paper aimed to summarize and revisit the three most recognized practice guidelines for the management and prevention of MRONJ, which were proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), and presented by the Journal of Bone and Mineral Research (JBMR) and the Journal of Clinical Oncology (JCO). Results and case studies: The AAOMS position paper focused on risk stratification by different medications, management decision trees, risk factors, pathophysiology, and disease staging. The JBMR international consensus presented eight focused questions, which were addressed by systematic reviews. The JCO clinical practice guideline presented six clinical questions, and each concluded with practical recommendations. Practical information was summarized and converted into an adoptable patient care workflow for clinicians to follow and apply in daily practice. Three case studies presented were treated following these guidelines. Each patient underwent advanced surgeries including alveoloplasty, tooth extraction, implant placement, and particulate bone grafting. Some of the considerations not fully informed were discussed and illustrated in each step of the patient care workflow, which included specifics for risk communication, updates on the use of antibiotics, biomarkers, and drug holidays. Conclusion and practical implications: Structured risk communication with official informed consent documentation should be considered before initiating invasive treatments. Disease control phase with home care therapy should be provided prior to staged reconstructive therapy. Drug holidays and antibiotics coverage can be customized based on individual conditions and related procedures with interprofessional coordination. [ABSTRACT FROM AUTHOR]

Background: A divergent fracture pattern is seen in patients living with type 1 diabetes (T1D). These patients are at risk for fractures at unusual distal sites over and above the fractures occurring at major osteoporotic sites. Avascular necrosis (AVN) involving the talus has not been reported previously in T1D. Case Presentation: We hereby report an exceptional case of a 24-year old patient of T1D, who reported to us 3 months post-partum with swelling and pain over her right ankle. In the third trimester of her pregnancy, she encountered trivial trauma to her right ankle. One month after delivery, she developed fragility fractures over her left 2nd to 4th metatarsal heads. On further workup, she was found to have low bone mass and avascular necrosis of right talus on magnetic resonance imaging. On follow up 1 year later, she continued to have low bone mass although her bone mineral density (BMD) increased at the lumbar spine and hip. She was diagnosed with right talar AVN due to fragility fracture sustained in the third trimester with low bone mass consequent to T1D. A possible role of pregnancy- and lactation-related osteoporosis was considered in view of the chronological association with pregnancy. Conclusion: Our case highlights the fragile skeletal health of patients living with T1D making a case for greater scrutiny of declining bone health in these patients. [ABSTRACT FROM AUTHOR]

Background: There has been no study in which the correlation between clinical results and dosimetry based on a 3D treatment planning system in patients with 198Au grains for head and neck cancer was evaluated. Methods: Thirty‐two patients who were treated with 198Au grains for head and neck cancer were reviewed. Twenty‐five patients were treated with brachytherapy alone and seven patients were treated with a combination of brachytherapy and neoadjuvant external beam radiation therapy. Results: With a median observation period of 60 months, the 5‐year local control rate was 82.9%. V85Gy of CTV in patients with local recurrence tended to be lower than that in patients without local recurrence (p = 0.07). The maximum dose of the keratinized gingiva in patients in whom bone exposure occurred was significantly higher than that in patients in whom bone exposure did not occur (p = 0.001). Conclusions: Dose distribution with 198Au grains can predict local control and late adverse events. [ABSTRACT FROM AUTHOR]

Background: Osteonecrosis of the femoral head (ONFH) is a significant postoperative complication following femoral neck fractures (FNFs) in adolescents, that has garnered considerable attention from researchers. Despite this interest, the incidence of ONFH in adolescents post-FNF surgery has not been extensively evaluated. To contribute to the body of research, we performed a meta-analysis utilizing articles sourced from multiple databases, with an emphasis on the rate of ONFH occurrence in young adolescents following FNF surgery. Objective: The purpose of this study was to investigate the incidence of ONFH after FNFs in adolescents worldwide and analyse potential risk factors affecting its occurrence to provide guidance for the treatment and rehabilitation after FNFs in adolescents and reduce the incidence of ONFH. Methods: A comprehensive search of medical literature databases, including MEDLINE, Web of Science, the Cochrane Library, and Embase, was conducted to identify relevant studies on ONFH and its associated risk factors after surgical treatment for FNFs in adolescents, covering the period from the establishment of the database to April 2024. Studies that did not meet the inclusion criteria were excluded. The study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Literature extraction, management, and data entry were performed using Zotero 6.0 and Excel 2016. The meta-analysis was conducted using R Studio 4.2.2. Subgroup analysis, sensitivity analysis, and assessment of publication bias were performed to explore sources of heterogeneity and evaluate the reliability of the results. This study has been registered on Prospero. (registration number: CRD4202452794; date of registration: 03/04/2024) Results: A total of 17 publications involving 862 patients with FNFs were included in this meta-analysis. The findings revealed that the incidence of ONFH after FNF surgery in adolescents was 24.02% [95% CI (0.2118, 0.2712)]. The included studies demonstrated good consistency, and no publication bias was observed. Conclusion: This study revealed that the incidence of ONFH after FNFs in adolescents is high (24.02%). Early screening and effective treatment of postoperative patients are crucial. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the feasibility and effectiveness of enhanced recovery after surgery (ERAS) in HIV-positive patients diagnosed with osteonecrosis of the femoral head (ONFH) undergoing total hip replacement (THR). Methods: We retrospectively included 80 HIV-positive patients diagnosed with ONFH who underwent THR between 2011 and 2022. Forty patients treated before August 2019 constituted the control group, receiving standard antiviral regimens and traditional perioperative management pathways. The remaining 40 patients, treated after August 2019, formed the study group, which followed the ERAS protocol. This protocol emphasized the use of more effective antiviral medications, rapid viral load reduction, immune enhancement, improved nutritional status, control of co-infections, prophylactic antibiotics, and anti-osteoporosis measures. We recorded patients' general status and imaging examinations before surgery, as well as detailed perioperative management strategies, antiviral regimens, durations, and immunological indicators for both groups. Targeted and standardized treatment measures were applied to the ERAS group, allowing for a comparison of the efficacy of perioperative management between the two patient groups. Results: Preoperative nutritional and immune indicators were lower in the control group than in the study group, while inflammatory markers were higher. Postoperatively, immune, nutritional, and inflammatory indicators were significantly better in the ERAS group compared to the control group. Following antiviral treatment, the viral load was predominantly undetectable in the ERAS group (target not detected, TND). Comprehensive measures minimized complications in the ERAS group (P = 0.028, P < 0.05). The hospitalization duration for the ERAS group was significantly shorter than that of the control group, with both groups showing marked improvement compared to preoperative conditions and no incidents of loosening or dislocation. Conclusion: Strengthening antiviral treatment, anti-infective strategies, incision care, and nutritional support effectively prevents and reduces complications such as delayed wound healing in HIV-positive patients. The implementation of ERAS measures requires careful attention to the patient's immune status, close monitoring of clinical changes, and timely adjustments to treatment and care plans. Level of evidence: Treatment studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusion Medication‐related osteonecrosis of the jaw (MRONJ) is a rare but debilitating disease characterized by a progressive necrosis of jaw bones in patients who have received anti‐resorptive or anti‐angiogenic therapies. Unfortunately, we still have no validated preventive or pharmaceutical interventions to help these patients, primarily due to our limited understanding of MRONJ pathogenesis. Here, we offer an extensive review of recent studies relevant to MRONJ pathogenesis. We present a hypothesis regarding the coupling of bone resorption and angiogenesis that relies on osteoblast‐derived, matrix‐bound vascular endothelial growth factors to explain why ONJ is associated with both anti‐resorptive and anti‐angiogenic agents.A narrative review was conducted by searching databases, including PubMed, Scopus, Google Scholar, and Web of Science, to retrieve relevant reports.Reduced bone resorption leads to reduced angiogenesis, and vice versa, creating a vicious cycle that ultimately results in ischemic necrosis of the jaw. Additionally, we suggest that reduced angiogenesis, induced by anti‐resorptive or anti‐angiogenic agents, aggravates bacterial infection‐induced bone necrosis, explaining why the jaw bone is particularly susceptible to necrosis.Our novel hypothesis will facilitate the advancement of future research and the development of more targeted approaches to managing MRONJ. [ABSTRACT FROM AUTHOR]

Background: Osteonecrosis of the femoral head (ONFH) is a progressive and debilitating condition characterized by the death of bone tissue due to inadequate blood supply. Despite advances in diagnostic imaging and treatment strategies, predicting the risk of femoral head collapse remains a significant clinical challenge. This study seeks to address this gap by developing a robust prognostic model that integrates clinical, imaging, and laboratory data to improve early diagnosis and guide therapeutic decision-making. Methods: We conducted a qualitative systematic review and employed the Delphi method to select key prognostic factors from clinical data, imaging findings, and laboratory indicators. The study included ONFH patients treated from January 2014 to December 2021. We used univariate and multivariate Cox regression analyses to develop a nomogram for predicting the risk of femoral head collapse. The model's performance was evaluated using the concordance index (C-index), calibration plots, and decision curve analysis (DCA). Results: The study included 297 patients (454 hips) with ONFH. Key prognostic factors identified included pain presence (p < 0.001, RR = 0.185, 95% CI: 0.11–0.31), JIC classification (C1: p < 0.001, RR = 0.096, 95% CI: 0.054–0.171; C2: p < 0.001, RR = 0.323, 95% CI: 0.215–0.487), necrotic area (3 < MNAI < 6: p < 0.001, RR = 0.107, 95% CI: 0.061–0.190; MNAI ≥ 6: p < 0.001, RR = 0.466, 95% CI: 0.314–0.692), weight-bearing reduction (p < 0.001, RR = 0.466, 95% CI: 0.323–0.672), preservation of the anterolateral pillar (p < 0.001, RR = 0.223, 95% CI: 0.223–0.473), and subchondral bone fracture on CT (p < 0.001, RR = 0.32, 95% CI: 0.217–0.472). The nomogram demonstrated a high C-index of 0.88, indicating excellent predictive accuracy. Calibration plots showed good agreement between predicted and observed outcomes, and DCA confirmed the model's clinical utility. Conclusions: The prognostic model developed in this study provides a reliable tool for predicting femoral head collapse in ONFH patients. It allows for early identification of high-risk patients, guiding personalized treatment strategies to improve patient outcomes and reduce the need for invasive surgical procedures. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusion This study aimed to analyze the factors affecting the occurrence of peri‐implant medication‐related osteonecrosis of the jaw (PI‐MRONJ) in patients using anti‐resorptive drugs (ARDs) on different implant position, inclinations, and types of prosthesis.The data of 75 patients with bone necrosis that progressed around the implant between 2018 and 2022 were retrospectively examined to identify the factors influencing PI‐MRONJ. Data, including patient demographics (age, sex, smoking status, concomitant disease, time of ARD therapy, dose of ARDs, and parafunctional habits) and implant‐specific information (type of prosthesis, angle of insertion), were extracted from medical and dental records.Tilted implants with an angle ≥ 5.1° relative to the occlusal plane of the prosthesis had a stronger association with PI‐MRONJ in comparison to non‐tilted implants (inclination was < 5°). Additionally, the boundary of the area of osteonecrosis around the fixture was larger for the splinted implant‐supported crowns than for the single implant supported crowns).In patients taking anti‐resorptive medications the inclination of the implant was associated with the occurrence of PI‐MRONJ. Further studies are required to confirm the clinical findings. [ABSTRACT FROM AUTHOR]

Background: Autologous bone cranioplasty is associated with a high complication rate, particularly infections and bone resorption. Although there are studies on the incidence and risk factors for complications following autologous bone cranioplasty, the study design is typically limited to retrospective analysis with multiple statistical explorations in small cohorts from single centers. Thus, there is a need for systematic analysis of aggregated data to determine the rate and risk factors for cranioplasty complications. Objective: To determine the incidence and risk factors for complications after autologous bone cranioplasty. Methods: In this systemic review, we conducted a Medline, Embase, Cochrane, and Web of Science search: 11,172 papers were identified. Duplicates were removed and only articles on complications following autologous bone cranioplasty between the years 2000 and 2022 were included. After title, abstract, and article screening, 132 papers were included for further analysis. Results: In total, the 132 studies are based on 13,592 patients (14960 implants). One third of the studies include patients with less than 3 months of postoperative follow-up. Complication management (flap removal, revision without flap removal, and conservative treatment) of infection, bone resorption, and hematoma/seromas are not reported in 19–30% of the studies. In the studies with defined complications management, the overall complication rate is 7.6% (95% Confidence Interval (CI) [7.1–8.2]) for infection, 14.4% (95% CI [13.7–15.2]) for bone resorption with indication for reconstruction, and 5.8%, (95% CI 5.2–6.5) for hematoma/seromas. Factors such as younger age, an extended interval between craniectomy and cranioplasty, the use of a fragmented bone implant, a larger implant size, and shunt treatment are linked to an increased risk of postoperative bone resorption. Conclusion: The lack of consistent definitions of complications, variations in follow-up time, and small study cohorts limit the external validity of many studies. Overall, the rate of bone flap resorption that required reoperation is high, while the rate of infectious complications is comparable to synthetic implants. Thus, autologous bone should preferably be used in cases without strong risk factors for bone necrosis. [ABSTRACT FROM AUTHOR]

In orthopedic surgery, precise bone screw insertion is crucial for stabilizing fractures, necessitating a preliminary cortical bone drilling procedure. However, this process can induce temperatures exceeding 70 °C due to the low thermal conductivity of cortical bone, potentially leading to thermal osteonecrosis. Furthermore, significant cutting forces and torque pose risks of tool breakage and bone damage, underlining the need for high precision and optimal processing parameters. Traditionally, drilling relies on the surgeon's experience and often results in imprecise outcomes due to inconsistent feed rates. Therefore, this study proposes the use of a 6-axis robot for controlled drilling, offering precise control over angular velocities and consistent feed rates. Additionally, explore the use of cryogenic liquid nitrogen (LN2) as a novel cooling method compared to conventional saline solutions, examining its efficacy under various cutting conditions. The results demonstrate that LN2 cooling conditions lead to a reduction in thrust and torque under specific processing conditions, and facilitate smoother chip evacuation. Additionally, LN2 significantly lowers the peak temperature around the drilling site, thus minimizing the risk of thermal osteonecrosis. Consequently, the use of a 6-axis robot provides consistent feed rates, and LN2 cooling achieves optimal processing conditions, enabling a more controlled and effective drilling process. [ABSTRACT FROM AUTHOR]

Purpose: The demographic and radiological risk factors of subchondral insufficiency fractures of the knee (SIFK) continue to be a subject of debate. The purpose of this study was to associate patient‐specific factors with SIFK in a large cohort of patients. Methods: Inclusion criteria consisted of patients with SIFK as verified on magnetic resonance imaging (MRI). All radiographs and MRIs were reviewed to assess characteristics such as meniscus tear presence and type, subchondral oedema presence and location, location of SIFK, mechanical limb alignment, osteoarthritis as assessed by Kellgren–Lawrence grade and ligamentous injury. A total of 253 patients (253 knees) were included, with 171 being female. The average body mass index (BMI) was 32.1 ± 7.0 kg/m2. Results: SIFK was more common in patients with medial meniscus tears (77.1%, 195/253) rather than tears of the lateral meniscus (14.6%, 37/253) (p < 0.001). Medial meniscus root and radial tears of the posterior horn were present in 71.1% (180/253) of patients. Ninety‐one percent (164/180) of medial meniscus posterior root and radial tears had an extrusion ≥3.0 mm. Eighty‐one percent (119/147) of patients with SIFK on the medial femoral condyle and 86.8% (105/121) of patients with SIFK on the medial tibial plateau had a medial meniscus tear. Varus knees had a significantly increased rate of SIFK on the medial femoral condyle in comparison to valgus knees (p = 0.016). Conclusion: In this large cohort of patients with SIFK, there was a high association with medial meniscus root and radial tears of the posterior horn, meniscus extrusion ≥3.0 mm as well as higher age, female gender and higher BMI. Additionally, there was a particularly strong association of medial compartment SIFK with medial meniscus tears. As SIFK is frequently undiagnosed, identifying patient‐specific demographic and radiological risk factors will help achieve a prompt diagnosis. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate and characterise articular cartilage degeneration in patients with osteonecrosis of the femoral head (ONFH) using T2 mapping magnetic resonance imaging. Methods: We reviewed 35 patients with ONFH (20 males and 15 females, mean age: 45.7 ± 12.9 years) without obvious cartilage abnormalities on plain magnetic resonance imaging (ONFH group) and 25 healthy volunteers (9 males and 16 females, mean age: 42.9 ± 5.8 years) (control group). All patients underwent T2 mapping magnetic resonance imaging after ONFH onset. The region of interest was defined as the weight-bearing portion of the articular cartilage in the femoral head and acetabulum in the coronal view. Results: The T2 values of the articular cartilage of the acetabulum and femoral head, including necrotic and normal regions, were significantly higher in the ONFH group than those in the control group. These T2 values of the acetabulum and femoral head in Stages 3A and 2 were significantly higher in the ONFH group than those in the control group. Conclusions: The articular cartilage of the acetabulum and femoral head can deteriorate after the onset of ONFH, which may affect the natural history of ONFH and ONFH treatment. Our findings suggest the need for early intervention in joint preservation surgery. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with Gaucher disease have a high risk of bone disease, with osteonecrosis representing the most debilitating complication. The pathogenesis of osteonecrosis has not been fully elucidated yet, and there is an unmet need for predictive biomarkers of bone complications. We aimed to assess the utility of angiogenesis and bone turnover biomarkers as predictors of osteonecrosis in Gaucher disease. Methods: Angiogenesis and bone turnover biomarkers were measured in 146 Gaucher disease patients (70M:76F, median age 49.5 [IQR 36.7 to 61]) with/without osteonecrosis enrolled in the UK-based registry GAUCHERITE [enrolment 2015–2017]. Receiver-operating characteristic curve analysis was used to compare the osteonecrosis predictive value of angiogenesis and bone turnover biomarkers and determine the optimal cut-off values for each biomarker. Results: Sixty-two patients had osteonecrosis before study enrolment, 11 had osteonecrosis during follow-up, and 73 remained osteonecrosis-free. Patients with osteonecrosis showed increased osteopontin and matrix metalloproteinase (MMP)-2 levels and decreased MMP-9 and vascular endothelial growth factor (VEGF)-C compared with those free from osteonecrosis. MMP-9 predicted future osteonecrosis with higher sensitivity and specificity (area under the receiver operating characteristic curve [AUC] 0.84 [95% CI 0.84–0.99]; sensitivity/specificity 82%/75%; cutoff value ≤ 72,420 pg/mL) than osteopontin, MMP-2 and VEGF-C when taken alone. The combination of MMP-9 and VEGF-C further increased the discriminating accuracy. Conclusions: The osteopontin–MMPs–VEGF axis is dysregulated in Gaucher disease patients with osteonecrosis. The combination of MMP-9 and VEGF-C circulating levels may serve to identify Gaucher disease patients at risk of osteonecrosis. [ABSTRACT FROM AUTHOR]

Introduction: Medication‐associated osteonecrosis of the jaws (MRONJ) is characterized by the presence of exposed bone or an intraoral or extraoral fistula in the maxillofacial region in patients with a history of treatment with anti‐resorptive and anti‐angiogenic drugs, such as monoclonal antibodies, and without a history of radiotherapy or metastatic diseases in the area. Objective: The aim of this study is to report a case of a pathological mandibular fracture in an area of MRONJ in a patient diagnosed with Crohn's disease treated with infliximab. Case report: A 53‐year‐old male patient, an active smoker for 35 years, diagnosed with Crohn's disease, undergoing intravenous administration of infliximab 300 mg for 1 year and 3 months, with no previous history of anti‐angiogenic or anti‐resorptive medication, presenting with an extraoral fistula in the submandibular region for 4 months, with painful symptoms, diagnosed as MRONJ. He was initially treated conservatively, using antimicrobial photodynamic therapy (aPDT), antibiotic therapy, and the PENTO protocol. However, the patient evolved with a pathological fracture in the mandibular parasymphysis, requiring surgical reconstruction. Final considerations: Pathological fracture of the mandible is a complication of MRONJ that compromises the patient's quality of life. The management of patients with MRONJ is complex and challenging. [ABSTRACT FROM AUTHOR]

Objective: Medication-related osteonecrosis of the jaw bones (MRONJ) is a well-known complication of antiresorptive and antiangiogenic drugs. Since the first report, more occurrences of MRONJ have been described worldwide. Dental extraction has been described by many studies as one of the risk factors for MRONJ. Comprehensive dental care (CDC) is a preventive dental method provided to patients prior to drug commencement. This study aims to determine the association between CDC and MRONJ. Patients and methods. A retrospective analysis was performed on 75 medical records of patients on antiresorptive and/or antiangiogenic drugs between February 2018 and May 2021. Demographics and clinical and radiographic data were collected. Univariate and multivariate analyses were performed to determine the factors associated with MRONJ. Results: Of the 75 patients who met the inclusion criteria, 11 (14.7%) developed MRONJ. Three out of 11 patients (27.2%) developed MRONJ spontaneously, while eight patients (72.8%) developed it after trauma from dentures or dental extractions. Following a binary logistic regression analysis, the lack of CDC was identified as a significant predictor of MRONJ. Patients who did not receive CDC had an odds ratio of 8.64 (95% confidence interval (CI): 1.27–58.62, p = 0.03). However, dental extraction did not show a statistically significant association with MRONJ in both the univariate and multivariate analyses. Conclusion: CDC before treatment with antiresorptive and antiangiogenic drugs is a potentially effective preventive method for reducing MRONJ. Dental extraction was not a significant factor in relation to MRONJ. [ABSTRACT FROM AUTHOR]

Our previous research revealed a close association between the acetylation of peroxisome proliferator-activated receptor γ (PPARγ) histone H3K27 and the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). We preliminarily explored the epigenetic mechanism of steroid-induced avascular necrosis of the femoral head (SANFH) development, but the specific histone deacetylase (HDAC) involved in this regulatory process remains unknown. In this study, we combined cell, animal, and clinical specimen experiments to screen for specific HDAC genes that could regulate BMSC adipogenic differentiation and to explore their roles. The results showed that dexamethasone (DEX) significantly exacerbated the imbalance between the adipogenic and osteogenic differentiation of BMSCs, and there were differences in HDAC expression in the adipogenic differentiation cell models, with histone deacetylase 10 (HDAC10) showing the most significant decrease in expression. Subsequent use of a chromatin immunoprecipitation assay kit and quantitative polymerase chain reaction (ChIP‒qPCR) revealed a decrease in HDAC10 expression at predicted potential sites within the PPARγ promoter, indicating a significant decrease in HDAC10 enrichment in the PPARγ promoter region of BMSCs, thereby promoting sustained PPARγ expression. Additionally, immunohistochemistry of samples collected from mice and humans with SANFH and normal femoral heads revealed an imbalance between adipogenic and osteogenic differentiation in the necrotic area of femoral heads, with a significant decrease in the relative expression of HDAC10 in the necrotic area of femoral heads with SANFH. In summary, we speculate that HDAC10 affects the progression of SANFH by regulating BMSC adipogenic differentiation, a process possibly related to PPARγ histone acetylation. These findings provide a promising direction for the treatment of SANFH. [ABSTRACT FROM AUTHOR]

The leading cause of steroid-induced femoral head osteonecrosis (ONFH) is the imbalance of bone homeostasis. Bone marrow-derived mesenchymal stem cell (BMSC) differentiation and fate are closely associated with bone homeostasis imbalance. Blocking monoacylglycerol lipase (MAGL) could effectively ameliorate ONFH by mitigating oxidative stress and apoptosis in BMSCs induced by glucocorticoids (GC). Nevertheless, whether MAGL inhibition can modulate the balance during BMSC differentiation, and therefore improve ONFH, remains elusive. Our study indicates that MAGL inhibition can effectively rescue the enhanced BMSC adipogenic differentiation caused by GC and promote their differentiation toward osteogenic lineages. Cannabinoid receptor 2 (CB2) is the direct downstream target of MAGL in BMSCs, rather than cannabinoid receptor 1(CB1). Using RNA sequencing analyses and a series of in vitro experiments, we confirm that the MAGL blockade-induced enhancement of BMSC osteogenic differentiation is primarily mediated by the phosphoinositide 3-kinases (PI3K)/ the serine/threonine kinase (AKT)/ (glycogen synthase kinase-3 beta) GSK3β pathway. Additionally, MAGL blockade can also reduce GC-induced bone resorption by directly suppressing osteoclastogenesis and indirectly reducing the expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) in BMSCs. Thus, our study proposes that the therapeutic effect of MAGL blockade on ONFH is partly mediated by restoring the balance of bone homeostasis and MAGL may be an effective therapeutic target for ONFH. [ABSTRACT FROM AUTHOR]

Purpose: We aim to compare interfragmentary compression with the position osteosynthesis in the fixation of different femoral neck fractures (FN) in synthetic bones subjected to vertical load. Methods: Forty-two synthetic femurs were subjected to neck fractures and separated into 3 groups according to the Pauwels classification: Pauwels I had 6 units (PI); Pauwels II, 24 units, with and without comminution (PII); and Pauwels III, 12 units, with and without comminution (PIII). After, they were fixed with 2 different ways: three 7, 0 mm cannulated lag screws (CSs) versus three 6, 5 mm solid fully threaded screws (SSs). Screws positioning was oriented by the Pauwels classification: inverted triangle or crossed screws. All specimens were submitted to vertical loading until failure. Results: The average force was 79.4 ± 22.6 Kgf. The greatest one was recorded in model 1 (135.6 Kgf), and the lowest in model 41 (39.6 Kgf). CSs and SSs had similar resistance until failure (p = 0.2). PI showed heightened resistance and PIII showed a worse response (p < 0,01). CSs had better performance in PIII (p = 0.048). Comminution and screws orientation caused no difference on peak force (p = 0.918 and p = 0.340, respectively). Conclusions: In synthetic bones, the resistance of a femoral neck fracture osteosynthesis using a 7, 0 mm cannulated lag screw or 6, 5 mm solid fully threaded screw are similar. There was no loss of efficiency with comminution in the femoral neck. Osteosynthesis resistance decreased with the verticalization of the fracture line and, in the more vertical ones, interfragmentary compression with CSs was more resistant than positional osteosynthesis with SSs. [ABSTRACT FROM AUTHOR]

Summary: Osteonecrosis (ON) is a common complication of glucocorticoid‐based Hodgkin lymphoma (HL) treatment, but the natural evolution and prognosis of ON lesions remain poorly understood. We describe the radiological evolution of ON lesions identified in a Nordic population‐based cohort of paediatric HL patients. Magnetic resonance images of suspected ON lesions were centrally reviewed to confirm ON diagnosis and grade the ON lesions according to the Niinimäki classification. The study included 202 ON lesions in 46 patients, of which 77 were joint lesions. Follow‐up images were available for 146/202 lesions, with a mean follow‐up time of 28 months. During follow‐up, 71% of the lesions remained stable, 26% improved or resolved, and 3% progressed. A higher ON grade at diagnosis was associated with a lower likelihood of spontaneous resolution. The likelihood for resolution of ON decreased by 50% for each year of added patient age, when adjusted for sex, ON location, and symptoms. Hip ON showed less spontaneous improvement compared with other joints, and the risk for surgery was 13‐fold in hip ON. Grades 3–4 joint ON has the potential to either progress or resolve, warranting follow‐up in patients with severe symptoms. Research on secondary prevention should be directed at grade 3–4 joint ON. [ABSTRACT FROM AUTHOR]

Corticosteroids play a crucial role as anti-inflammatory and immunomodulatory agents in dermatology and other medical specialties; however, their therapeutic benefits are accompanied by significant risks, especially in older adults. This review examines the broad spectrum of adverse effects (AEs) associated with oral corticosteroid therapy and offers strategies to prevent, monitor, and manage these issues effectively in older adults. AEs associated with systemic corticosteroids include immune suppression, gastrointestinal problems, hyperglycemia, insulin resistance, weight gain, cardiovascular complications, ocular issues, osteoporosis, osteonecrosis, muscle weakness, collagen impairment, psychiatric symptoms, and adrenal suppression. To minimize these AEs, tailored dosing and duration, frequent monitoring, and additional preventative measures can be employed to optimize corticosteroid treatment. By customizing management plans to the specific needs and risk factors associated with each patient, clinicians can promote the safe and effective use of oral corticosteroids, ultimately improving outcomes and quality of life in patients with inflammatory dermatologic disorders. [ABSTRACT FROM AUTHOR]

Background: Osgood–Schlatter disease (OSD) belongs to the group of sterile bone necrosis and mainly affects athletically active children. The pathogenesis of OSD is currently not fully understood, so the purpose of this study was to evaluate the concentrations of selected matrix metalloproteinases (MMPs)—MMP-2, MMP-3, MMP-7, MMP-9, MMP-10 and MMP-26 in patients diagnosed with OSD compared to patients with diseases other than sterile bone necrosis Methods: The study group included 140 patients with OSD, while the control group contained 100 patients with knee pain unrelated to sterile bone necrosis. The MMPs tested were determined by an enzyme-linked immunosorbent assay in plasma. Results: Patients with OSD had higher concentrations of MMP-2 and MMP-9 compared to the control group. The concentrations of MMP-7, MMP-10 and MMP-26 were lower in affected children. High values of diagnostic parameters—diagnostic accuracy (AC), sensitivity (SE), specificity (SP) and area under curve (AUC)—were obtained for MMP-7, MMP-9 and MMP-26. Conclusions: The collected results convince that MMP-7, MMP-9 and MMP-26 can be consider as a differential ancillary test between OSD and other knee pain and may be involved in the pathogenesis of this condition. [ABSTRACT FROM AUTHOR]

Objectives: Anti‐resorptive agents have been linked to the development of MRONJ in patients undergoing dental surgical procedures. This survey aims to explore the level of knowledge and experience of Italian Society of Periodontology and Implantology members in the management of patients treated with anti‐resorptive agents and with the risk of developing MRONJ. Materials and Methods: An 18‐item questionnaire was submitted by e‐mail to the SIdP members. Statistical analyses were carried out. Continuous variables were described as mean ± standard deviation (SD) or median, and first and third quartile according to distribution's normality. Normality of data was checked with Shapiro–Wilk test. Results: Four hundred and fifty‐one questionnaires were returned by e‐mail (32%). Most of the respondents were private practitioners (81.8%). Only 47.7% declared to be highly confident in managing patients on anti‐resorptive therapy while 92.5% reported to have performed tooth extractions and 52.3% implant surgery in patients under anti‐resorptive therapy for osteometabolic disorders. One or more MRONJ‐affected patients were encountered by 63.2% of the respondents. Conclusions: This survey highlights the need to develop a "dedicated" program both for dentists and prescribers to improve the level of cooperation and to increase the level of awareness of patients treated with anti‐resorptive agents. [ABSTRACT FROM AUTHOR]

Purpose: A nationwide multicenter follow-up cohort study of hip replacement arthroplasties performed for nontraumatic osteonecrosis of the femoral head (ONFH) aimed to answer the following questions: What factors were associated with need for reoperation? Although many modifications were made in bipolar hemiarthroplasties (BPs) to improve their durability, could we find any evidence of their efficacy? Methods: Excluding 58 infected hips and 43 ABS THAs with very poor survivorship, we analyzed 7393 arthroplasties; 6284 total hip arthroplasties (THAs), 886 BPs, 188 total resurfacing arthroplasties, and 35 hemi-resurfacing arthroplasties (hRSs). In the 886 BPs, 440 hips had a smooth small-diameter prosthetic neck (nBPs), 667 hips had a smooth neck (sBPs), 116 hips had highly cross-linked polyethylene in the outer head (hBPs), and 238 hips had an outer head whose outer surface was alumina ceramic (aBPs) (648 hips had an outer head whose outer surface was metal [mBPs]). Multivariate analyses using a Cox proportional-hazard model analyzed risk factors. Results: Follow-up ranged from 0.1 to 27 (average, 6.9) years, during which 265 hips (3.6%) needed reoperation. Combined systemic steroid use and excessive alcohol consumption and lateral approach were associated with higher risks, aBPs were less durable than THAs or mBPs, and hRSs were inferior to the others. Regarding BPs, the following divisions did not influence their survivorship; nBP or not, sBP or not, and hBP or not. Conclusions: Factors associated with reoperation risk were identified as described above. The modifications made in BPs did not improve their durability, but aBPs made it worse. Level of clinical evidence: Level III, therapeutic cohort study. [ABSTRACT FROM AUTHOR]

Purpose: To examine the frequency of patellofemoral joint (PFJ) osteoarthritis (OA) and its symptoms in the long-term course of open-wedge high tibial osteotomy (OWHTO). Methods: We analyzed 113 joints of 91 patients. OA and osteonecrosis (ON) developed in 91 and 22 joints, after an average postoperative period of 127.5 ± 19.5 months. For X-ray evaluation, the standing femorotibial angle (FTA), % mechanical axis (%MA), Caton–Deschamps index (CDI), patellar tilt angle (TA), lateral patellar shift (LPS), and PFJ space width (medial [MJS] and lateral [LJS]) were analyzed. PFJ-associated symptoms were evaluated using the hospital for special surgery patellar score (HSS-PS) and knee injury and osteoarthritis outcome score patellofemoral subscale (KOOS-PF). Statistical analysis was performed with paired and unpaired t tests, and a risk rate of less than 1% was significantly judged. Results: Preoperative FTA and CDI decreased from 180.8° to 170.0° and 0.88 to 0.70 at the final follow-up. Preoperative %MA lateralized from 20.8 to 66.0 at the final follow-up. TA and LPS values decreased significantly compared with before surgery until plate removal. The MJS and LJS significantly decreased, and OA with a joint space < 3 mm occurred in 14 cases. However, HSS-PS and KOOS-PF scores were not significantly different between the groups with and without OA. Conclusion: PFJ OA occurred in 12.4% cases in the long-term postoperative course of OWHTO; however, no symptomatic difference was found in the group with or without OA. [ABSTRACT FROM AUTHOR]

Femoral head avascular necrosis (AVN) can contribute to substantial functional limitation. Although surgical intervention for advanced staged AVN can be useful, non-surgical interventions to improve functional independence of patients with hip AVN are not well described. The purpose of this case report is to describe the physical therapy intervention provided to a patient with bilateral hip AVN. The patient was a 56-year-old male presenting to physical therapy with bilateral femoral head AVN. Impairment-based manual therapy, therapeutic exercise, and education were provided to promote decreased pain and improved self-reported function. The patient completed eight visits over the course of 10 weeks. Clinically significant improvements were noted in pain ratings and functional level as measured by the Lower Extremity Functional Scale and Harris Hip Score. Improvements were maintained at a two-year follow up period. Early identification and physical therapy intervention can contribute to promoting functional independence for patients with bilateral hip AVN. Early intervention could potentially reduce the need for surgical intervention. Further research is necessary to describe with detail the optimal methods to accomplish these goals. [ABSTRACT FROM AUTHOR]

This study aimed to report the collective clinical characteristics of oral side effects associated with imatinib therapy according to age, sex, and clinical condition. A bibliographic review was performed using the PubMed, Web of Science, Scopus, Cochrane Library, and Embase databases. Forty-five cases of oral side effects due to imatinib therapy were identified in the literature. With the addition of five new cases seen at the authors' institution, a total of 50 cases were analysed. Of the five new cases, four with gastrointestinal stromal tumours developed oral lichenoid lesions (OLLs), and one with chronic myeloid leukaemia (CML) developed oral hyperpigmentation (OHP). Of the total 50 patients, 26 were male and 24 were female, and age ranged from 29 to 86 years. Most patients were ≥50 years old (80%); only three patients were jaw was the least common, with just five cases (10%). Among the patients with OHP, the predominant clinical condition was CML (22 cases, 91.7%). In conclusion, the possibility of oral side effects needs to be considered during the examination of patients receiving imatinib therapy. [ABSTRACT FROM AUTHOR]

Cortical bone drilling is integral to orthopedic and dental surgeries, yet challenges such as thermal necrosis persist. Previous finite element (FE) models may overlook critical parameters, impacting accuracy. This study aims to integrate experimental and computational approaches to predict essential parameters—initial temperature, point angle, and spindle speed—enhancing precision in cortical bone drilling. Bovine cortical samples were utilized to systematically investigate the impact of four independent parameters on maximum temperature (MT) and maximum thrust force (MTF). Parameters included drill bit initial temperature (IT), diameter, point angle, and spindle speed (225–2700 rpm, feed rate 0.5–3 mm/s). Experimental procedures involved an orthopedic handpiece with titanium drill bits. DEFORM-3D V6.02 facilitated FE simulation, with the validated model developed for the second stage of the drilling process. The validated model highlighted the significant impact of drill bit IT on MT, predicting a 26.14 % decrease in final bone temperature as IT decreased from 25 to 5 °C. Increasing the point angle from 70 to 120° resulted in a 13.1 % MT increase and a 26.9 % decrease in MTF. Spindle speed variations exhibited a 48.3 % temperature increase and an 82.8 % MTF decrease. Integrating experimental validation and computational modeling offers a comprehensive approach to predict drilling parameters. Precision in cortical bone drilling can be optimized by selecting specific parameters, including lower drill bit IT, smaller point angles, and controlled spindle speeds. This optimization reduces the risk of bone necrosis and thermal damage, thereby enhancing surgical outcomes. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors are at increased risk of developing (long-term) skeletal adverse effects, such as osteonecrosis, impaired bone mineral density, and fractures. This paper provides an overview of the current understanding of bone health in these survivors, examining whether it represents a significant concern. It focusses on the challenges of assessing and managing bone health in childhood cancer survivors, highlighting diagnostic pitfalls, methods for accurately identifying those at high risk, and suggested strategies for the surveillance and management of osteonecrosis and impaired bone mineral density. The need for improved surveillance strategies, particularly for high-risk survivors, alongside potential prevention and management options, including pharmacological and lifestyle interventions, is emphasised. Given the lack of consensus on optimal prevention and treatment strategies, the paper emphasises the need for further research to optimise care and improve long-term outcomes for childhood cancer survivors with bone health impairments.