We compared bone and muscle strength and related factors between children with autism spectrum disorder (ASD) and typically developing children (TDC). We included 15 male children with ASD (mean age: 10.3, SD: 2.7 years) and 45 TDC (11.4, 1.8), matched for sex, age, maturity, height and body mass. We used pQCT to assess bone strength, area, and content at the distal and shaft sites of the radius and tibia, as well as muscle area at the forearm and lower leg. We measured grip strength and long jump distance and recorded daily physical activity (PA) and vitamin D, calcium, and protein intakes. We used site-specific multivariate analyses of covariance to compare bone outcomes, adjusting for muscle area. We compared PA and nutrient intakes using multivariate analyses, and muscle area and performance outcomes using analysis of variance. Children with ASD had 13-31% lower bone strength, area, and content at the shaft sites of the radius and tibia, and distal tibia. They also had 26-33% lower grip strength and long jump distances, spent 76% more daily time in light PA, and accumulated 67% fewer bone impact counts compared with TDC. We report deficits in bone strength and content accompanied by lower muscle strength performance and fewer bone-impacting activities in male children with ASD. Future research should determine whether lower muscle strength and reduced bone-loading exposure contribute to bone deficits and may serve as targets to optimize bone development.
Bone metabolism is regulated by immune cells that maintain skeletal homeostasis through cytokine secretion and cell interactions. Disruption of this regulation-by inflammation, autoimmunity, or aging-drives pathological bone diseases including osteoporosis and rheumatoid arthritis. Single-cell technologies and exosome biology have revealed previously unrecognized immune subsets and regulatory layers within the bone microenvironment. Osteoimmunology has elucidated the interplay between macrophages, T cells, B cells, NK cells, neutrophils, dendritic cells, and mast cells in bone remodeling. These cells form dynamic interaction networks-Treg-M2 feedback loops, Th17-neutrophil amplification, and B-T-osteoclast axes-that collectively determine net skeletal outcome. Immune cells regulate osteoclast and osteoblast function through TNF-α, IL-6, IL-17 A, and RANKL, with highly context-dependent effects. Immunosenescence has emerged as a key driver of age-related bone loss. The RANKL/RANK/OPG axis serves as the central signaling hub, modulated by Sema3A/Wnt/β-catenin, PI3K/Akt, JAK/STAT, and Notch. Dysregulation of these pathways underlies osteoporosis, RA, intervertebral disc degeneration, ankylosing spondylitis, and cancer bone metastasis. Clinically, denosumab and cytokine-targeted biologics (anti-TNF-α, anti-IL-6R, anti-IL-17 A) demonstrate bone-protective effects, while bispecific antibodies, CAR-Treg cells, and senolytics represent emerging strategies. The net skeletal effect of the immune system is determined by the balance of interacting cell types, cytokine networks, and signaling pathways. Future progress requires single-cell spatiotemporal multi-omics, cell-type-specific immunotherapies, elucidation of the gut-bone axis, and systematic evaluation of combination strategies pairing immunomodulators with anti-resorptives, anabolic agents, or senolytics.
This technical innovation describes a surgical approach that reuses autogenous bone plates harvested from the lateral maxillary sinus wall during lateral sinus floor elevation for simultaneous ridge augmentation. The technique integrates sinus augmentation and bone harvesting within a single operative field, eliminating the need for a secondary donor site. The harvested bone plate is polished and fixed to form a rigid cortical shell, following the principles of the bone shell technique. Clinical application in a preliminary case series demonstrated predictable bone regeneration, with horizontal bone gain of 4.18 (2.44) mm and a resorption rate of 11.96 (11.57) % at 1 mm apical to the alveolar crest. Mean harvested bone plate thickness was 1.20 (0.36) mm. No major complications were observed, and all implants were successfully placed after healing. The lateral maxillary sinus wall represents a viable donor site, enabling effective augmentation while avoiding additional donor-site morbidity.
Bone invasion is a strong indicator of a poor prognosis in head and neck squamous cell carcinoma (HNSCC), although the underlying mechanisms are still unclear. Due to the limited resolution of bulk sequencing, the specific malignant epithelial cell (EPC) subpopulation responsible for bone invasion and its regulatory network have long been unclear. We developed a comprehensive cellular atlas of EPCs in bone-invasive HNSCC using single-cell transcriptome sequencing, and we carefully examined their subpopulation heterogeneity, functional states, and transcriptional regulatory networks. The primary subpopulation found to be associated with bone invasion was the C2 ITGA6⁺ EPC. Mechanistically, these intermediate transitional cells may facilitate bone invasion via an epithelial-mesenchymal transition program controlled by TP63, with connections between the tumor microenvironment regulated by LAMININ and EPHB signaling. This discovery may help develop customized treatment options by providing a novel single-cell-resolution viewpoint on the molecular associations underlying bone-invasive HNSCC.
Secondary hyperparathyroidism is a common complication of chronic kidney disease that accelerates bone loss and increases fracture risk. While parathyroidectomy (PTx) is the definitive treatment for medically refractory cases, its impact on bone mineral density (BMD) has not been comprehensively evaluated. A systematic search of PubMed, Embase, and Scopus was conducted from inception through January 2026. Studies were included if they reported dual-energy X-ray absorptiometry-measured BMD before and after PTx in adults with secondary hyperparathyroidism due to chronic kidney disease. Two reviewers independently screened and selected studies using the PICOS framework, and additional articles were identified through reference searching. Across 11 studies encompassing 452 patients with paired measurements, all demonstrated significant improvement in BMD following a site-specific hierarchy favoring cancellous bone. The lumbar spine (+7-50% g/cm2) and femoral neck (+8-23% g/cm2) showed the most consistent gains, while the distal radius showed minimal change. Higher preoperative parathyroid hormone levels, elevated alkaline phosphatase, and lower baseline BMD were associated with greater skeletal recovery. The only available randomized trial confirmed the superiority of PTx over cinacalcet for bone density improvement. PTx consistently improves BMD in patients with refractory secondary hyperparathyroidism, with the greatest gains at cancellous-rich skeletal sites. Clinicians should consider the skeletal benefits of PTx when counseling patients with medically refractory disease, particularly those with low baseline bone density and markedly elevated parathyroid hormone levels.
Puberty is a critical window for bone mass acquisition, determining lifelong fracture risk. Gonadotropin-releasing hormone agonist (GnRHa)-based pubertal suppression followed by gender-affirming hormone therapy (GAHT) is increasingly used in transgender and gender-diverse (TGD) adolescents, raising concerns about peak bone mass. To quantify changes in bone mineral density (BMD), bone mineral apparent density (BMAD), and z scores in TGD adolescents undergoing GnRHa with or without GAHT, and to identify predictors of skeletal outcomes. PubMed, Scopus, Web of Science, and Cochrane Library, from inception through September 2025. Longitudinal cohorts assessing BMD, BMAD, or z scores at the lumbar spine, total hip, or femoral neck in TGD adolescents treated with GnRHa with or without GAHT. Ten studies met the inclusion criteria. Data were extracted in duplicate; study quality was assessed using the Newcastle-Ottawa Scale. Random-effects models pooled mean changes across baseline (time 0 [T0]), after GnRHa (T1), and after GAHT (T2), stratified by skeletal site and sex assigned at birth. Metaregressions examined body mass index, age, Tanner stage, and treatment duration. Dual-energy x-ray absorptiometry-derived BMD, BMAD, and z scores. Ten cohorts comprising 751 adolescents (427 assigned female at birth [AFAB]; 324 assigned male at birth [AMAB]) were included. Lumbar spine z scores declined during GnRHa (AFAB: z-score change, -0.97 [95% CI, -1.09 to -0.85]; AMAB: z-score change, -0.73 [95% CI, -0.93 to -0.53]) despite stable BMD. z Scores used sex-assigned-at-birth normative references. After GAHT, BMD increased (AFAB: BMD mean difference, 0.09 g/cm2 [95% CI, 0.07-0.10 g/cm2]; AMAB: BMD mean difference, 0.13 g/cm2 [95% CI, 0.10-0.16 g/cm2]), with partial z-score recovery; values remained below baseline at T2 (AFAB: z-score change, -0.51 [95% CI, -0.69 to -0.34]; AMAB: z-score change, -0.52 [95% CI, -0.82 to -0.21]) but were not consistently statistically different across skeletal sites. Recovery at the total hip and femoral neck was smaller and more heterogeneous. Higher body mass index, shorter GnRHa duration, and longer GAHT exposure were associated with more favorable outcomes. This systematic review and meta-analysis found that pubertal suppression followed by GAHT was associated with transient z-score reductions and subsequent BMD increases. At T2, z scores remained numerically below baseline but were not consistently statistically different, suggesting an uncertain rather than demonstrated persistent deficit. Timely GAHT initiation is recommended.
Anterior shoulder instability is a common condition, frequently seen in young and active individuals. For patients with critical glenoid bone defects (≥15%), Bankart repair has limited effectiveness and bony augmentation surgery is often required. However, traditional bone grafts carry the risk of graft resorption, while 3D-printed personalised implants aimed at anatomical reconstruction face limitations in accessibility, cost and production time. In this multicentre, randomised controlled trial, anterior shoulder instability patients with critical glenoid bone loss will be screened across five centres. Individuals with multidirectional shoulder instability, concomitant ipsilateral shoulder injuries, concurrent diseases that may affect the joint or those ineligible for surgical intervention will be excluded.Randomisation will be performed in a 1:1 ratio, stratified by age, physical activity level and trial centre. Participants will receive either iliac crest bone grafting (ICBG) or glenoid reconstruction with screw-type implant. The primary analysis will be the difference of the Rowe score between ICBG and glenoid reconstruction patients at 1 year postoperatively. We set the non-inferiority margin at 6 points, corresponding to 60% of the MCID to ensure the clinical relevance of the non-inferiority test. Funded by the Medical Scientific Research Project of the First Affiliated Hospital of Chongqing Medical University (2025QDLXZX-07); Ethics Committee of the First Affiliated Hospital of Chongqing Medical University approved (ZZ2025-938-01). Final results will be updated on trial registries and submitted to a peer-reviewed journal and provide a novel treatment option for patients with anterior shoulder instability and offer a theoretical foundation and evidence base for the development of treatment strategies for similar cases in the future. ChiCtr2500115163.
Substantial recent advances in percutaneous image-guided minimally invasive interventions provide a robust arsenal for radiologists in management of patients with bone tumors. Percutaneous minimally invasive thermal ablation, cementation with or without osseous reinforcement via implants, and osteosynthesis have been successfully used and progressively incorporated into the management paradigm of patients with bone tumors. The purpose of this article is to outline the recent advances in such interventions and the role of radiologists in managing patients with bone tumors in modern-era practice.
Severe sleep disturbances are highly prevalent in secondary hyperparathyroidism. While parathyroidectomy corrects biochemical abnormalities, longitudinal evidence elucidating mechanisms driving sleep improvement remains scarce. A total of 443 secondary hyperparathyroidism patients undergoing parathyroidectomy from 2 independent centers were enrolled. Biochemical parameters, bone pain/pruritus (visual analog scale), and sleep quality (Pittsburgh Sleep Quality Index) were longitudinally assessed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Linear mixed-effects models characterized sleep trajectories. Temporal cascaded parallel mediation models were constructed to test the sequence: 1-week parathyroid hormone → 1-month symptoms → 3-month sleep. Baseline sleep disturbance rates were 73.6% and 78.2% across cohorts. Postoperatively, sleep quality exhibited stepwise improvement, with 3-month Pittsburgh Sleep Quality Index scores significantly decreasing by 7.19 and 8.08 points, respectively (both P < .001). Structural equation modeling demonstrated that the direct effect of 1-week parathyroid hormone decline on 3-month sleep was nonsignificant. Instead, indirect pathways via alleviated bone pain and pruritus were highly significant, indicating that sleep improvement was predominantly mediated by symptom relief rather than a direct hormonal effect. This pattern remained consistent across unadjusted and fully adjusted models. In this 3-month observational study, postparathyroidectomy sleep improvement is not primarily driven by a direct effect of parathyroid hormone reduction but is predominantly mediated by a temporal pathway: biochemical correction → symptom relief (bone pain and pruritus) → sleep improvement.
Vertebral bone metastases are frequent in oncological patients and lead to a significant risk of vertebral fractures. Computational modelling offers a valuable tool for investigating how metastatic lesions affect the mechanical stability and integrity of the spine. This study presents the development of a Python-based algorithm for a 3D subject-specific parametric finite element model (SS-parFEM) designed to semi-automatically generate simplified spine segments that reproduce deformation patterns similar to those observed experimentally. The model represents a metastatic vertebra including the lesion and an adjacent healthy vertebra separated by an intervertebral disc, with geometry and mean trabecular and cortical bone material properties derived from computed tomography (CT) images. By applying the experimentally measured axial compressive failure loads, predicted principal strain fields were compared with full-field experimental data obtained from Digital Volume Correlation (DVC). Good agreement in spatial strain patterns was observed, suggesting the model's ability to capture the main features of the mechanical response of metastatic vertebrae, although peak strain magnitudes were not fully reproduced. The framework was further applied to investigate the mechanical influence of lesion type and the bone-metastasis interface. The preliminary findings suggest that interface bonding conditions can affect load transfer and stress distributions in blastic lesions, whereas lytic lesions exhibited a mechanical behaviour largely independent of interface integrity. This adaptable parametric approach provides a foundation for future subject-specific investigations and offers a useful tool for biomechanical studies of metastatic spine stability.
Bone and soft tissue sarcomas harboring EWSR1::NFATC2 and FUS::NFATC2 fusions (NFATC2-rearranged sarcomas) is a recently defined entity with a morphologic spectrum and clinical behavior that are not fully elucidated. We studied 32 such sarcomas that occurred in 21 male and 11 female patients. The EWSR1::NFATC2 fusion was found in tumors of 25 patients (17 M, 8 F; median age: 40, range: 14-78), 16 of which arose in soft tissue, while 8 originated in bone. Morphologically, they showed relatively consistent morphologic features yet variable degrees of cytologic atypia, mitotic rates and necrosis. Follow-up (19 patients; median: 22 months, range: 1-70) demonstrated local recurrence in 3 patients, while distant metastases occurred in 6 patients. Two patients died of disease (DOD), 4 were alive with disease (AWD) and 13 were without evidence of disease (AWOD). In contrast, the FUS::NFATC2 fusion was exclusively seen in osseous tumors, which occurred in 7 patients (4 M, 3 F; median age: 32, range: 4-62). Further, FUS::NFATC2 tumors showed significant morphologic heterogeneity. Follow-up (6 patients; median: 18 months, range: 13-60) demonstrated local recurrence in 2 patients, and lung metastases in 2 patients. At last follow-up, 3 patients were AWD, while 3 patients were AWOD. Using a two-tiered grading scheme based on cytologic atypia, mitotic rate, and necrosis, patients with low-grade tumors experienced significantly fewer adverse events than those classified as high-grade (p=0.026); however, estimated metastasis-free survival was not statistically significant due to our limited sample size. Overall, our study expands on the morphologic spectrum of NFATC2-rearranged sarcomas and highlights the clinicopathologic, molecular, and genetic differences between the EWSR1- and FUS-rearranged tumors. Although additional long-term follow-up data is required, our study further suggests that a subset of these sarcomas have a protracted clinical course while high-grade morphologic features such as atypia, mitotic activity and necrosis may correlate with worse behavior.
Metabolic bone diseases are diverse disorders marked by impaired bone turnover or mineralization, causing fragility and fractures. Interventional radiology (IR) plays a key role by offering minimally invasive treatments for pain relief, stabilization, and early mobilization. Vertebroplasty is effective for painful osteoporotic vertebral fractures without deformity, while kyphoplasty or expandable devices suit cases with collapse or kyphosis. In Kümmell's disease, targeted cement augmentation provides rapid improvement. Sacral insufficiency fractures can be safely treated with computed tomography-guided sacroplasty, enabling early ambulation. Complex sacral fractures may require combined fixation and sacroplasty. Overall, IR enhances outcomes and reduces complications in frail patients.
Sensorineural hearing loss (SNHL) and vestibular symptoms in sickle cell disease (SCD) may result from hypoxic damage of inner ear structures, including the stria vascularis (SV), spiral ganglion cells (SGC), and vestibular ganglion neurons (VGN). SV cross-sectional area, SGC counts, and VGN counts were compared between SCD and control groups and correlated with temporal bone histopathology and clinical data. Hematoxylin and eosin-stained slides from 36 temporal bones were analyzed, including both ears from 6 SCD cases and 12 controls matched for age, sex, and race. A deep learning model was developed to measure SV area, total ear SGC counts, and VGN counts. Single and multivariable analyses were performed to compare histopathologic correlates between groups and available clinical data. The mean age was 19 ± 7.8 years for the SCD group [male: n = 3 (50%); black/African American: n = 6 (100%)] and 19 ± 6.7 years for controls [male: n = 6 (50%); black/African American: n = 10 (83%)]. Mean pure tone averages were normal for both groups (SCD = 12.2 ± 10.4; control = 11.1 ± 7.8, P = 0.84). SV area was similar in the SCD group compared with controls at the basal turn, middle turn, and apex; however, qualitative analysis of individual cases revealed signs of atrophy in a higher proportion of SCD cases. No significant difference was found in SGC (SCD = 25,721 ± 3283; control = 24,585 ± 5016, P = 0.43) or VGN counts (SCD = 20,673 ± 2294; control = 21,275 ± 4948, P = 0.68) between groups. The remainder of cochlear structures were preserved. SV area, SGC, and VGN populations are preserved in primarily young individuals with SCD and normal hearing. Otopathologic correlates of SNHL in SCD may manifest following the onset of hearing loss.
A woman in her 20s presented with a 3-month history of progressive right-sided otalgia. Otoendoscopic examination revealed a greyish mass occluding more than 75% of the external auditory canal. Biopsy confirmed well-differentiated squamous cell carcinoma. High-resolution CT demonstrated cortical erosions of the anterior and posterior bony external auditory canal with mastoid involvement. The patient underwent two-handed endoscopic lateral temporal bone resection using the Justtach ASM2 endoscope holder, combined with superficial parotidectomy and selective neck dissection. Histopathological examination confirmed complete excision with negative margins. The patient received adjuvant chemoradiation therapy and remains disease-free at follow-up. This case demonstrates the technical feasibility of a two-handed endoscopic approach for temporal bone malignancy resection, though larger studies are needed to establish its efficacy compared with conventional microscopic techniques.
To investigate whether tibiofemoral bone and meniscus morphology were associated with dynamic anterior tibial translation (ATTd) and internal tibial rotation (ITRd) during jump-landing tasks in anterior cruciate ligament (ACL)-reconstructed knees. Results may provide some guidance on the use of additional surgical procedures alongside (revision) ACL reconstruction (ACLR). Patients who underwent primary ACLR were included. Morphological features were measured using pre-surgery magnetic resonance images of the operated knee. Dependent variables included ATTd and ITRd during the landing of the single-leg hop for distance (SLHD) and side hop (SH), measured with three-dimensional optoelectronic motion capture. Univariate statistical parametric mapping regression analyses were conducted with morphological features as predictors. Thirty patients were included at 4.7 ± 1.8 years post-ACLR (age: 31.0 ± 4.8 years). Steeper sagittal-plane lateral posterior tibial slope and greater medial-lateral difference in posterior tibial slope were significantly associated with less ATTd (peak r = -0.75; p = 0.048) and greater ITRd (peak r = 0.75; p = 0.047) during the SLHD and SH, but only in ACL-reconstructed knees with a flat medial tibial plateau (-2° to +2°; n = 13 subgroup analysis). Steeper coronal-plane tibial slope was significantly associated with less ATTd during the SLHD (peak r = -0.45; p = 0.049), and with greater ITRd during the SH (peak r = 0.47; p = 0.047). Smaller lateral meniscal slope of the posterior horn was significantly associated with greater ITRd during the SLHD (peak r = -0.46; p = 0.047). Greater lateral femoral condyle ratio was significantly associated with greater ITRd during the SLHD (peak r = 0.46; p = 0.04) and SH (peak r = 0.56; p = 0.006). The observed associations with greater ITRd warrant further investigation into the potential role of anterolateral corner reconstruction alongside (revision) ACLR in patients with these morphological features. Since associations between posterior tibial slopes and ITRd depended on a flat medial plateau, the role of slope-reducing tibial osteotomy appears limited, as these procedures typically do not selectively target a single plateau. Level II.
The probe-to-bone (PTB) is a simple, bedside clinical test that can assist in diagnosis of diabetic foot osteomyelitis (OM). The utility of PTB varies depending on the population, with a lower positive predictive value in lower-risk outpatients. This is a protocol for a pilot, feasibility and safety multi-centre randomized controlled trial. 80 patients, with PTB diabetic foot ulcers and without initial X-ray findings of OM, will be randomized to 2 weeks antibiotic therapy or 6 weeks of antibiotic therapy at a 1:1 ratio. The primary outcomes will be to assess feasibility (eligibility to recruitment ratio, retention rate, adherence to protocol and cross-over from intervention to control group) and safety (serious adverse events, antibiotic-associated adverse events, Clostridium difficile associated diarrhea and hospitalization) in this cohort. Exploratory clinical outcomes will include recommencement/continuation of antibiotic therapy or requirement for surgery, and the proportion of participants that demonstrate new radiological changes of OM on serial X-ray imaging. Follow-up will occur at 14 days, 42 days and 90 days post-recruitment. This is the first randomised trial assessing the feasibility and safety of shorter antibiotic therapies in patients with low-risk PTB diabetic foot ulcers. The findings of this trial will inform the design of future large multi-site randomised trials to risk stratify diabetic foot ulcers and better understand how to treat diabetic foot OM. Australian New Zealand Clinical Trials Registry (ANZCTR): 12624000266561. Registered on 15/03/2024.Registration URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386823&isReview=true.
To investigate effects of repeated training with anatomically varied versus identical 3D-printed models on skill acquisition, cognitive load, and skill retention in novice mastoidectomy trainees. A prospective, randomized, controlled, educational trial conducted April to September 2024 including a 3-month retention test. Simulation center at a single academic teaching hospital. Twenty-four novice medical students were randomized 1:1 into 2 groups: The Identical Models (IM) group practiced repeated procedures on identical 3D-printed temporal bone models (control) and the Variable Model (VM) group practiced on a varied selection of models (intervention). Trainees completed 10 anatomical mastoidectomy procedures with posterior tympanotomy followed by 2 retention test procedures after 3-months of nonpractice. The primary outcome was performance assessed with 25-point modified Welling Scale. The secondary outcome was cognitive load estimated by relative reaction time measured on a secondary task. At end-of-training, the VM group scored 20.6 points (95% CI [19.2-22.0]), outperforming the IM group who scored an average of 18.2 points (95% CI [16.7-19.6], P = .02). At 3‑month retention testing, the VM group's scores decayed by a mean of 5.6 points on the repeated model (95% CI [-7.2 to-4.0], P < .001) and of 3.7 points when introduced to a new model (95% CI [-5.2 to-2.1], P < .001). The IM group showed no decay thereby demonstrating better skill retention which aligned with reduced relative reaction time (cognitive load) during training. Educators can optimize mastoidectomy skills acquisition and retention by instructional design that prioritize repeated practice on anatomically identical models until basic skills have been acquired.
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