Lithium prevents glucocorticoid-induced osteonecrosis of the femoral head by regulating autophagy.

Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.

BMP6 and VDR gene polymorphisms are associated with osteonecrosis in a sickle cell anaemia cohort.

The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.

miR-486-5p Attenuates Steroid-Induced Adipogenesis and Osteonecrosis of the Femoral Head Via TBX2/P21 Axis.

Enhanced adipogenic differentiation of mesenchymal stem cells (MSCs) is considered as a major risk factor for steroid-induced osteonecrosis of the femoral head (SOFNH). The role of microRNAs during this process has sparked interest. miR-486-5p expression was down-regulated significantly in femoral head bone tissues of both SONFH patients and rat models. The purpose of this study was to reveal the role of miR-486-5p on MSCs adipogenesis and SONFH progression. The present study showed that miR-486-5p could significantly inhibit adipogenesis of 3T3-L1 cells by suppressing mitotic clonal expansion (MCE). And upregulated expression of P21, which was caused by miR-486-5p mediated TBX2 decrease, was responsible for inhibited MCE. Further, miR-486-5p was demonstrated to effectively inhibit steroid-induced fat formation in the femoral head and prevented SONFH progression in a rat model. Considering the potent effects of miR-486-5p on attenuating adipogenesis, it seems to be a promising target for the treatment of SONFH.

Deep learning enables the differentiation between early and late stages of hip avascular necrosis.

OBJECTIVES: To develop a deep learning methodology that distinguishes early from late stages of avascular necrosis of the hip (AVN) to determine treatment decisions. METHODS: Three convolutional neural networks (CNNs) VGG-16, Inception ResnetV2, InceptionV3 were trained with transfer learning (ImageNet) and finetuned with a retrospectively collected cohort of (n = 104) MRI examinations of AVN patients, to differentiate between early (ARCO 1-2) and late (ARCO 3-4) stages. A consensus CNN ensemble decision was recorded as the agreement of at least two CNNs. CNN and ensemble performance was benchmarked on an independent cohort of 49 patients from another country and was compared to the performance of two MSK radiologists. CNN performance was expressed with areas under the curve (AUC), the respective 95% confidence intervals (CIs) and precision, and recall and f1-scores. AUCs were compared with DeLong's test. RESULTS: On internal testing, Inception-ResnetV2 achieved the highest individual performance with an AUC of 99.7% (95%CI 99-100%), followed by InceptionV3 and VGG-16 with AUCs of 99.3% (95%CI 98.4-100%) and 97.3% (95%CI 95.5-99.2%) respectively. The CNN ensemble the same AUCs Inception ResnetV2. On external validation, model performance dropped with VGG-16 achieving the highest individual AUC of 78.9% (95%CI 51.6-79.6%) The best external performance was achieved by the model ensemble with an AUC of 85.5% (95%CI 72.2-93.9%). No significant difference was found between the CNN ensemble and expert MSK radiologists (p = 0.22 and 0.092 respectively). CONCLUSION: An externally validated CNN ensemble accurately distinguishes between the early and late stages of AVN and has comparable performance to expert MSK radiologists. CLINICAL RELEVANCE STATEMENT: This paper introduces the use of deep learning for the differentiation between early and late avascular necrosis of the hip, assisting in a complex clinical decision that can determine the choice between conservative and surgical treatment. KEY POINTS: • A convolutional neural network ensemble achieved excellent performance in distinguishing between early and late avascular necrosis. • The performance of the deep learning method was similar to the performance of expert readers.

Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone destruction in the maxillofacial region. Dental surgery, including tooth extractions, commonly trigger the onset of MRONJ. While guidelines suggest avoiding extraction when possible, complete avoidance is not always feasible, as necrosis can develop from dental and periodontal disease without dental procedures. The goal of this article is to provide an update review of current preventive and therapeutic approaches for MRONJ. METHODS: A comprehensive electronic search was conducted on PubMed/MEDLINE, Embase, and Scopus databases. All English articles encompassing randomized controlled trials, systematic reviews, observational studies, and case studies were reviewed. The current medical treatments and adjuvant therapies for managing MRONJ patients were critically assessed and summarized. RESULTS: Pentoxifylline and alpha tocopherol (PENT-E), teriparatide, photobiomodulation (PBM), photodynamic therapy (PDT), and the use of growth factors have shown to enhance healing in MRONJ patients. Implementing these methods alone or in conjunction with surgical treatment has been linked to reduced discomfort and improved wound healing and increased new bone formation. DISCUSSION: While several adjuvant treatment modalities exhibit promising results in facilitating the healing process, current clinical practice guidelines predominantly recommend antibiotic therapy as a non-surgical approach, primarily addressing secondary infections in necrotic areas. However, this mainly addresses the potential infectious complication of MRONJ. Medical approaches including PENT-E, teriparatide, PBM, and PDT can result in successful management and should be considered prior to taking a surgical approach. Combined medical management for both preventing and managing MRONJ holds potential for achieving optimal clinical outcomes and avoiding surgical intervention, requiring further validation through larger studies and controlled trials.

MiR-601-induced BMSCs senescence accelerates steroid-induced osteonecrosis of the femoral head progression by targeting SIRT1.

BACKGROUND: The imbalance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is not only the primary pathological feature but also a major contributor to the pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH). Cellular senescence is one of the main causes of imbalanced BMSCs differentiation. The purpose of this study was to reveal whether cellular senescence could participate in the progression of SONFH and the related mechanisms. METHODS: The rat SONFH model was constructed, and rat BMSCs were extracted. Aging-related indicators were detected by SA-ß-Gal staining, qRT-PCR and Western Blot experiments. Using H2O2 to construct a senescent cell model, and overexpressing and knocking down miR-601 and SIRT1 in hBMSCs, the effect on BMSCs differentiation was explored by qRT-PCR, Western Blot experiment, oil red O staining (ORO), alizarin red staining (ARS), and luciferase reporter gene experiment. A rat SONFH model was established to test the effects of miR-601 and metformin in vivo. RESULTS: The current study showed that glucocorticoids (GCs)-induced BMSCs senescence, which caused imbalanced osteogenesis and adipogenesis of BMSCs, was responsible for the SONFH progression. Further, elevated miR-601 caused by GCs was demonstrated to contribute to BMSCs senescence through targeting SIRT1. In addition, the anti-aging drug metformin was shown to be able to alleviate GCs-induced BMSCs senescence and SONFH progression. CONCLUSIONS: Considering the role of BMSCs aging in the progression of SONFH, this provides a new idea for the prevention and treatment of SONFH.

Treatment of AVN-Induced Proximal Pole Scaphoid Nonunion Using a Fifth and Fourth Extensor Compartmental Artery as a Vascularized Pedicle Bone Graft: A Retrospective Case Series.

BACKGROUND Scaphoid nonunion (SN) is a challenging condition in wrist pathology, often resulting in severe consequences if left untreated. Surgical intervention, particularly using vascularized bone grafts (VBGs), is a promising but uncertain approach. The 4+5 extensor compartment artery (ECA) pedicled graft, less commonly used for SN, has potential benefits due to its vascular supply and accessibility to the scaphoid. This study aimed to evaluate the effectiveness of the 4+5 ECA pedicled graft combined with headless compression screw fixation in treating avascular necrosis (AVN)-induced proximal pole SN. Radiological results, functional outcomes, and complications related to this method were assessed. MATERIAL AND METHODS This was a retrospective analysis of 19 proximal pole SN cases with AVN treated using the 4+5 ECA-VBG technique from 2016 to 2022. Patients underwent preoperative evaluation and postoperative follow-up for at least 1 year. Data on surgery, demographics, radiological assessments, and functional outcomes were recorded and analyzed statistically. RESULTS All patients achieved radiographic union within 8.5 weeks postoperatively, with revascularization of proximal pole necrosis. Significant improvements in functional outcomes were observed, including pain reduction, increased wrist range of motion, improved grip and pinch strength, and enhanced wrist scores. No major complications were reported. CONCLUSIONS The 4+5 ECA-VBG technique, with headless compression screw fixation, showed high success rates in treating AVN-induced proximal pole SN. This method offers comprehensive restoration of wrist function and minimal complications, making it a viable option for SN management, especially in AVN cases. Further research is needed to confirm these results and establish standardized protocols for SN treatment.

In vivo study of porous NiTi cryotweezers for bone tissue cryotherapy.

This study examined the effects of liquid nitrogen vapor on osteogenesis in the rabbit femur. Cryotweezers made of porous nickel titanium alloy (nitinol or NiTi) obtained by self-propagating high temperature synthesis were used in this experiment. The porous structure of the cryotweezers allows them to hold up to 10 g of liquid nitrogen after being immersed for 2 min, which completely evaporates after 160 s. To study the effects of liquid nitrogen evaporation on osteogenesis, a rabbit femur was perforated. The formed holes were subjected to cryotherapy with varying exposure times. It was found that a 3 s exposure time stimulates osteogenesis, which was manifested in a greater number of osteoblasts in the regenerate compared to the control sample without liquid nitrogen. It was observed that increasing the exposure to 6, 9 or 12 s had a destructive effect, to varying degrees. The most severe damage was exerted by a 12 s exposure, which resulted in the formation of osteonecrosis areas. In the samples exposed to 6 and 9 s of cryotherapy, destruction of the cytoplasm of osteocytes and osteoclasts was observed.

Osteonecrosis of the Knee: The Unintended Consequence of Steroid Abuse.

The anti-inflammatory and immunosuppressive properties of steroids allow their use in a wide variety of rheumatological diseases, asthma, inflammatory bowel disease, cancer therapy, and severe viral infections. Though life-saving or organ-saving, long-term clinical use leads to a vast array of complications. Osteoporosis is the most common orthopedic side effect of steroid abuse, while osteonecrosis is a rare occurrence. The risk of osteonecrosis appears to be dose and duration dependent, but several patient factors also play a major role and usually affect the femoral head followed by the knee joint. The long-term effects of steroids must be explained to all patients on therapy, but this risk is missed in individuals who abuse steroids for recreational or performance-enhancing purposes. We describe a male, aged 29 years, who presented with dull aching bilateral knee pain of 2-years' duration after a long-term steroid abuse for weight and muscle mass gain. Radiological and magnetic resonance imaging studies confirmed osteonecrosis of femoral and tibial condyles and secondary degenerative arthritis of the knee joint. Prompt suspicion, early diagnosis, and intervention in osteonecrosis of knee joints, and termination of steroids may reverse the pathology and prevent progression of disease.

Risk Factors for Infection Recurrence After Surgical Resection of Advanced Stage Osteonecrosis of the Mandible.

BACKGROUND: Advanced stage osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are challenging disease entities requiring multimodal therapy including surgical resection. However, risk factors associated with infection recurrence are poorly understood. PURPOSE: The purpose of this study was to identify risk factors associated with infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study including patients who underwent segmental mandibulectomy for management of ORN or MRONJ between 2016 and 2021 at the authors' institution. Subjects who did not have margin viability data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was viability of resection margins on histopathologic analysis (viable or nonviable). Secondarily, other risk factors categorized as demographic (age, sex, race), medical (comorbidities), and perioperative (reconstructive modality, antibiotic duration, microbiological growth) were evaluated. MAIN OUTCOME VARIABLE: The primary outcome variable was time to infection recurrence defined as time from surgical resection to clinical diagnosis of a fistula tract, abscess, or persistent inflammatory symptoms necessitating surgical intervention. COVARIATES: Not applicable. ANALYSES: Descriptive and bivariate statistics were used to identify associations between risk factors and time to infection recurrence. A significance level of P ≤ .05 was considered significant. RESULTS: The cohort consisted of 57 subjects with a mean age of 63.3 ± 10.0 years (71.9% Male, 75.4% White) treated for ORN (47.4%) or MRONJ (52.6%). A total of 19/57 (33%) subjects developed a recurrence of infection with 1 and 2 year survival of 75.8 and 66.2%, respectively. Nonviable resection margins were associated with earlier time to infection recurrence (P ≤ .001, hazard ratio (HR) = 11.9, 95% confidence interval (CI) = 3.84 to 36.7) as was younger age (P = .005, HR = 0.921, 95% CI = 0.869 to 0.976) and atypical pathogen growth on culture (P = .002, HR = 8.58, 95% CI = 2.24 to 32.8). CONCLUSIONS AND RELEVANCE: Histopathologic margin viability was associated with earlier time to infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. Additional studies are needed to identify interventions that may improve outcomes in this demographic.

Natural course of talar avascular necrosis during short-term follow-up and factors associated with Disease progression.

BACKGROUND: This retrospective cohort study aimed to investigate the natural history of talar avascular necrosis (AVN) during short-term outpatient follow-up and to identify the risk factors for progression to collapse and arthritic changes. METHODS: Thirty-four cases of talar AVN from 34 patients (15 males, 19 females) were included. The mean age of the patients was 48.9 years (SD 16.0 years) and the mean follow-up period was 39.5 months (SD 42.0 months). The patients were divided into two groups i.e., progression and non-progression groups. The progression group consisted of those who showed aggravation of the Ficat stage during the follow-up period or advanced arthritis of the ankle joint (Ficat stage 4) at presentation. Demographic data and information regarding BMI, medical comorbidities, trauma history, bilaterality, and location of the lesion (shoulder vs. non-shoulder lesions) were collected. Following the univariate analysis, a binary logistic regression analysis was performed. RESULTS: The location of the talar AVN was the only significant factor (p = 0.047) associated with disease progression. A total of 14.3% (2 of 14) of the central (non-shoulder) talar AVN lesions showed progression, while 50% (10 of 20) of shoulder lesions aggravated during follow-up. Age, sex, bilaterality, medical comorbidities, and trauma history were not associated with progressive talar collapse or subsequent arthritic changes in talar AVN. CONCLUSIONS: Conservative treatment should be considered for a central lesion of the talar AVN because it tends to remain stable without progression. A more comprehensive study with a larger study population is required to establish the surgical indications for talar AVN. LEVEL OF EVIDENCE: Prognostic level III.

Total hip arthroplasty after failed transtrochanteric rotational osteotomy for osteonecrosis of the femoral head: analysis of three-dimensional morphological features.

BACKGROUND: In total hip arthroplasty (THA) after failed transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the femoral head (ONFH), deformity of the proximal femur has been reported to affect stem placement. The aims of this study were to evaluate the morphological changes in the proximal femur, muscle atrophy, and soft tissue thickening in THA after TRO and the clinical outcomes. METHODS: The TRO group included 17 patients (18 hips) who underwent THA after failed TRO. The control group included 21 patients (28 hips) who underwent primary THA for ONFH. To evaluate the deformity of the proximal femur before THA, we measured the anteroposterior and mediolateral diameters of the femur on computed tomographic slices 5 mm proximal to the lesser trochanter. To evaluate muscle atrophy and soft tissue thickening, we measured the thicknesses of the psoas major, iliac, and gluteus medius muscles and the anterior capsule of the hip joint. RESULTS: The ratio of the anteroposterior to mediolateral diameters of the proximal femur was significantly greater in the TRO group (p < 0.01). The thicknesses of the muscles did not differ between the two groups, whereas the anterior capsule was significantly thicker in the TRO group (p < 0.05). Varus or valgus stem alignment (> 3°) was frequent in the TRO group (p < 0.01). CONCLUSIONS: The round shape of the proximal femur was deformed after TRO compared with primary THA for ONFH, which may have caused malposition of the stem. In addition, we should pay attention to anterior protrusion of the proximal femur and thickening of the anterior capsule.

Modified osteochondral autograft transplantation for steroid-induced osteonecrosis of femoral head in idiopathic thrombocytopenic purpura: a case report and literature.

Osteochondral autograft transplantation (OAT) has been commonly applied in the knee and ankle while the technique has not yet been a popularity in the femoral head. In this article, we present a 28-year-old female patient, who has a history of 1-year-use of glucocorticoid in the treatment of idiopathic thrombocytopenic purpura, with steroid-induced osteonecrosis of the femoral head (SONFH). She underwent surgical hip dislocation, osteochondroplasty, OAT, and internal fixation. Her Harris Hip Score improved from 64 to 82 in 36 months to follow-up. The case is valuable considering that a single, instead of several, 1.5 cm autograft was harvested from the non-bearing part of the same femoral head. This modification dispensed with the need of surgery for harvesting autograft from knee or ankle and reduced the structural vulnerability brought by the multihole donor part of the femoral head.

The small screw-apex distance is potentially associated with femoral head osteonecrosis in adults with femoral neck fractures treated by closed reduction and percutaneous 3 parallel cannulated screws.

OBJECTIVE: Femoral neck fractures (FNFs) are among the most common fractures in elderly individuals. Surgery is the main treatment for FNFs, and osteonecrosis of the femoral head (ONFH) is one of the unacceptable complications. This study aimed to assess both the clinical and radiological outcomes in patients with FNFs treated with three parallel cannulated screws and to identify relationship between screws position and ONFH. PATIENTS AND METHODS: A total of 100 patients who were treated with closed reduction and fixed with 3 parallel cannulated screws met the inclusion criteria between January 2014 and December 2020 at authors' institution. The follow-up duration, age, sex, affected side, and injury-to-surgery interval were collected; the neck-shaft angle of both hips, screw-apex distance (SAD) and the tip-apex distance (TAD)were measured; and the Garden classification, quality of reduction and presence of ONFH were evaluated. RESULTS: The sample consisted of 37 males and 63 females, with 60 left and 40 right hips affected. The mean age of patients was 54.93 ± 12.24 years, and the mean follow-up was 56.3 ± 13.38 months. The overall incidence of ONFH was 13%. No significant difference was observed in the incidence of ONFH by affected side, age, fracture displacement, injury-to-surgery interval, neck-shaft angle deviation, or reduction quality. The SAD was significantly shorter in ONFH patients than in normal patients for all three screws (p = 0.02, 0.02, and 0.01, respectively). CONCLUSIONS: The short SAD of all screws is associated with femoral head necrosis of FNFs treated with 3 cannulated screws. The short SAD indicated that screws malpositioning in the weight-bearing area of the femoral head, potentially harming the blood supply and compromising the anchorage of the primary compressive trabeculae in this region.

Association between cup orientation and low back pain after total hip arthroplasty in patients with osteonecrosis of the femoral head.

BACKGROUND: Postoperative low back pain (LBP) following total hip arthroplasty (THA) is classified as secondary hip-spine syndrome. The purpose of this study was to explore the correlations between cup orientation of THA and postoperative LBP in patients with osteonecrosis of the femoral head (ONFH). METHODS: A retrospective cohort study included 364 ONFH patients who underwent bilateral THA between January 2011 and December 2020. Among them, 53 patients (14.6%) experienced postoperative LBP at the end of follow-up and were designated as pain group (PG). A control group (CG) consisting of 106 patients with similar age, sex, and body mass index (BMI) to those in the PG was selected. Postoperative LBP in the PG was assessed using the visual analogue scale (VAS). Demographic data, clinical information, and radiographic criteria were evaluated as potential predictors of LBP. RESULTS: Patients in PG (mean age, 47.3 years [range, 27 to 75 years]; 42 [79%] male) had a mean VAS score of 4.6 (range, 1 to 9) compared with 0 for the patients in CG (mean age, 47.6 years [range, 19 to 77 years]; 84 [79%] male). There were no significant differences in clinical data between the two groups (p > 0.05). Preoperative radiographic variables also showed no significant differences between the PG and CG (p > 0.05). However, the postoperative inclination, anteversion, and standing ante-inclination (AI) were significantly lower in the PG compared to the CG, whereas the sitting and standing sacral slope (SS) were significantly higher (p < 0.05). Moreover, the variations in standing AI, standing and sitting pelvic tilt (PT) were significantly lower in the PG compared to the CG, while the variations in standing and sitting SS and lumbar lordosis (LL) were significantly higher (p < 0.05). The variation in standing AI in the PG showed a significantly correlation with the variation of standing SS, standing PT, and LL (p < 0.05). CONCLUSION: Postoperative LBP in ONFH patients after bilateral THA is significantly associated with the intraoperative cup orientation. The variation in standing AI is correlated with the variations in standing SS, standing PT, and LL, potentially contributing to the development of postoperative LBP.

Taxifolin-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of glucocorticoid-induced osteonecrosis of the femoral head.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is the main complication secondary to long-term or excessive use of glucocorticoids (GCs). Taxifolin (TAX) is a natural antioxidant with various pharmacological effects, such as antioxidative stress and antiapoptotic properties. The purpose of this study was to explore whether TAX could regulate oxidative stress and apoptosis in GIONFH by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. We conducted qRT-PCR, Western blotting, TUNEL assays, flow cytometry, and other experiments in vitro. Microcomputed tomography analysis, hematoxylin-eosin staining, and immunohistochemical staining were performed to determine the therapeutic effect of TAX in vivo. TAX mitigated the overexpression of ROS and NOX gene expression induced by DEX, effectively reducing oxidative stress. Additionally, TAX could alleviate DEX-induced osteoblast apoptosis, as evidenced by qRT-PCR, Western blotting, and other experimental techniques. Our in vivo studies further demonstrated that TAX mitigates the progression of GIONFH in rats by combating oxidative stress and apoptosis. Mechanistic exploration revealed that TAX thwarts the progression of GIONFH through the activation of the Nrf2 pathway. Overall, our research herein reports that TAX-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of GIONFH.

Transphyseal Fracture of the Distal Humerus.

Transphyseal fractures of the distal humerus often occur in children younger than 4 years as a result of birth trauma, nonaccidental trauma, or falls from a low height. It is important to identify and treat these injuries in a timely manner to ensure successful management. Most transphyseal fractures of the distal humerus are treated with closed reduction and percutaneous pinning with the aid of an elbow arthrogram. The most common complication following a fracture is cubitus varus caused by growth arrest, malunion, or osteonecrosis of the medial condyle. Normal carrying angles may be restored through corrective lateral closing wedge osteotomy.

Biomechanical analysis of alveolar bones with compromised quality supporting a 4-unit implant bridge; a possible association with implant-related sequestration (IRS).

OBJECTIVES: This study aimed to investigate the strain in the bone surrounding dental implants supporting a 4-unit bridge and assess the role of excessive strain as a possible risk factor for implant related sequestration (IRS) or peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ). MATERIALS AND METHODS: A 3D-mandibular model was constructed using computed tomography and segmented it into cortical and cancellous bones. The 4-unit implant-supported bridges replacing the mandibular posteriors were constructed, and each featuring two, three, and four implants, respectively. The Young's modulus was assigned based on the quality of the bone. A maximum occlusal force of 200 N was applied to each implant in the axial and in a 30-degree oblique direction. RESULTS: The maximum principal strain of the fatigue failure range (> 3000 µÎµ) in the bone was analyzed. The volume fraction of fatigue failure was higher in poor-quality bone compared to normal bone and oblique load than in axial load. An increasing number of implants may dissipate excessive strain in poor-quality bones. CONCLUSIONS: Occlusal force applied to poor-quality bone can result in microdamage. Given that unrepaired microdamage may initiate medication-related osteonecrosis of the jaw, long-term occlusal force on fragile bones might be a risk factor. CLINICAL RELEVANCE: When planning implant treatment for patients with compromised bone status, clinical modifications such as strategic placement of implants and optimization of restoration morphology should be considered to reduce excessive strain which might be associated with IRS or PI-MRONJ.

The assessment of halitosis with a new screening tool in medication-related osteonecrosis of the jaw.

OBJECTIVES: This study aimed to identify the levels of halitosis in patients with Medication-related osteonecrosis of the jaw (MRONJ) and osteoporosis and to suggest a new MRONJ screening method using halitosis measurement. MATERIALS AND METHODS: From October 2019 to April 2023, participants aged 19 years or older without periodontal disease were selected. Seventy-five participants, 25 in each group, were divided into an MRONJ group, an osteoporosis group without MRONJ, and a control group without osteoporosis and not taking osteoporosis drugs or antibiotics. Each participant underwent halitosis assessment twice using an exhaled breath analyzer to measure halitosis twice by blowing a straw for 1 min. Measured concentrations of hydrogen, hydrogen sulfide, and methyl mercaptan were compared between groups. RESULTS: Data from 22 patients in the MRONJ group, 25 in the osteoporosis group, and 25 in the control group were analyzed. The concentrations of hydrogen sulfide and methyl mercaptan were significantly higher in the MRONJ group than in the other groups, but the concentrations of hydrogen did not differ between the groups. When comparing the concentrations of hydrogen sulfide and methyl mercaptan in osteoporosis patients and solid cancer patients in the MRONJ group, there was a significant difference in hydrogen sulfide concentration, but there was no significant difference in methyl mercaptan. CONCLUSIONS: Quantifying the level of halitosis can be used to screen for MRONJ in patients taking bisphosphonates, such as patients with osteoporosis, prostate cancer, and breast cancer. CLINICAL RELEVANCE: MRONJ is accompanied by bad breath, and the concentrations of hydrogen sulfide and methyl mercaptan are associated with MRONJ.

No increased risk of osteonecrosis of the jaw in osteoporotic patients with dental implants: a nationwide cohort study.

OBJECTIVES: The occurrence of implant-associated osteonecrosis of the jaw (ONJ) has been reported in osteoporotic patients, particularly in association with bisphosphonate therapy. This study aimed to investigate the risk of implant surgery and implant presence for ONJ occurrence in osteoporotic patients longitudinally. METHODS: Based on Korean National Health Information Database, subjects over the age of 65 who were diagnosed with osteoporosis between July 2014 and December 2016 were included. The implant group included subjects who had undergone dental implant surgery between January 2017 and December 2017, while the control group included those who had no history of dental implants. The primary outcome was the occurrence of ONJ, and the date of final follow-up was December 2020. RESULTS: A total of 332,728 subjects with osteoporosis were included in the analysis: 83,182 in the implant group and 249,546 in the control group. The risk of ONJ among those who had undergone implant surgery (risk of implant surgery-associated ONJ) was not higher than that among those without implant surgery. The risk of ONJ among those with implants (risk of implant presence-associated ONJ) was lower than that among those without implants. Even in subjects with a history of bisphosphonates, steroids, periodontitis, or tooth extraction, those who had undergone implant surgery or had implants did not have a higher ONJ risk than those who had not undergone surgery or did not have implants; rather, they showed a lower risk. CONCLUSIONS: The results may suggest that dental implants are not associated with an increased risk of ONJ. A further study on whether dental implants are associated with lower ONJ risk is needed. CLINICAL RELEVANCE: Dental implants did not increase the risk of ONJ development in osteoporotic patients, even with a history of bisphosphonates. This may suggest that the risk profiles for ONJ occurrence between selective insertion of dental implants and other dentoalveolar surgery associated with infectious conditions are different.