Osteosarcoma is the most common malignant bone tumor in children and adolescents, which predominantly arises in the metaphyses of long bones. Characterized by high malignancy and a high tendency toward pulmonary metastasis, it confers a poor patient prognosis. At present, the standard-of-care therapy consists of radical wide resection combined with postoperative adjuvant radiotherapy and chemotherapy. Nevertheless, invasive treatments such as chemotherapy are accompanied by prominent adverse reactions. Accordingly, non-invasive and safe physical therapies have gained growing research interest. As a non-invasive physical therapeutic modality, pulsed electromagnetic fields (PEMF) have exhibited anti-tumor activities against multiple malignancies. However, its therapeutic efficacy, underlying molecular mechanisms, and influences on normal bone tissue in osteosarcoma remain poorly understood. Methods In this study, osteosarcoma cell lines and osteoblast cell lines were exposed to pulsed electromagnetic fields in vitro, with untreated cells set as the control group. CCK-8 and Transwell assays were performed to evaluate cell proliferation, migration and cell death. Western blotting and quantitative real-time PCR (qPCR) were used to detect the expression levels of key ferroptosis-related molecules and lipid peroxidation markers. Furthermore, the in-vivo anti-tumor effect of PEMF was verified using a nude-mouse osteosarcoma metastatic tumor model. Cytological and animal behavioral assays were applied to assess bone mineral density, trabecular architecture and osteogenic differentiation markers of normal bone tissue. Results PEMF markedly suppressed the proliferation and migration of osteosarcoma cells and triggered ferroptosis, manifested by down-regulated expression of GPX4 and SLC7A11 as well as elevated malondialdehyde (MDA) levels. The above-mentioned phenotypes could be partially reversed by the ferroptosis inhibitor deferoxamine (DFO). In vivo experiments demonstrated that PEMF significantly reduced the number of pulmonary metastatic lesions and prolonged the survival time of nude mice. Meanwhile, PEMF facilitated osteoblast differentiation and improved bone mineral density and trabecular-bone-related parameters, without obvious damage observed to normal bone tissue. Clinical implications and limitations This study indicates that PEMF represents a promising non-invasive adjuvant therapeutic option after osteosarcoma resection. It can inhibit tumor metastasis as well as promote bone repair, and therefore possesses potential for clinical translation. Nonetheless, evaluations regarding long-term safety and effectiveness are still absent. The adopted electromagnetic-field parameters and frequency range are relatively limited. Further multi-parameter optimization and validation in larger-scale animal models are required.
Background Patients with metastatic bone disease affecting the femur are at substantial risk of pathologic fracture, resulting in significant morbidity and frequently necessitating urgent surgical intervention. Accurate identification of lesions at imminent risk of fracture enables timely prophylactic fixation and improved patient outcomes. Although the Mirels score remains widely used, its limited specificity has prompted interest in CT-derived biomechanical approaches, including CT-based Structural Rigidity Analysis (CTRA) and Finite Element Analysis (FEA). Whole-femur CT is routinely obtained in some specialist orthopaedic oncology pathways, including our own, but this practice is not universal; many centres rely initially on clinical assessment and plain radiographs, with CT reserved for selected cases. We systematically reviewed the literature to compare evidence for Mirels, CTRA, and CT-based FEA in predicting pathologic femoral fractures. Methods A systematic search of MEDLINE and Embase was performed for studies published between 2005 and 2025. Eligible studies evaluated Mirels scoring, CTRA, or CT-based FEA in adult patients with femoral metastatic disease and reported subsequent pathologic femoral fracture outcomes. Two reviewers independently screened studies and extracted data. Potential cohort overlap was assessed by comparing authorship, recruiting institutions, enrolment periods, eligibility criteria, and descriptions of prior datasets. Management after fracture-risk assessment was examined to identify intervention-related bias. Due to heterogeneity in study design, imaging methods, and outcome reporting, a qualitative narrative synthesis was undertaken. Results Eight studies met the inclusion criteria, comprising prospective and retrospective clinical cohorts, an implementation study, and one illustrative comparative case series. In studies reporting formal diagnostic estimates, Mirels sensitivity ranged from 66.7% to 88%, while specificity ranged from 38% to 47.9%. In the principal prospective comparison, CTRA achieved 100% sensitivity and 60.6% specificity. Across formal FEA analyses, sensitivity ranged from 80% to 100% and specificity from 67% to 86%, although modelling methods, thresholds, and comparators varied. The evidence arose from small, partly overlapping cohorts, and prophylactic stabilization of lesions considered high risk limited observation of untreated outcomes and particularly the positive predictive value. Heterogeneity precluded meta-analysis. Conclusion Mirels remains a useful, accessible, and sensitive first-line screening tool, particularly where plain radiography is the principal imaging modality. CTRA and CT-based FEA may offer additional specificity and objective mechanical information in selected patients where suitable calibrated CT imaging and technical expertise are available, but current evidence does not support replacing clinical assessment and radiography. Whole-femur CT is routine in some specialist pathways, including our own, but not across all centres. Further progress will require prospective multicentre validation, standardized methodologies, health-economic assessment, and integration within multidisciplinary team pathways.
Introduction:Patients with bone metastases (BM) from non-small cell lung cancer (NSCLC) derive less clinical benefit from immune checkpoint inhibitors (ICIs) than those without skeletal involvement. We aimed to characterize bone-specific disease control profiles under first-line ICI therapy and explore the association of denosumab with clinical outcomes. Methods:We conducted a multicenter retrospective study in BM-NSCLC patients, naïve to systemic therapy, treated with first-line ICI monotherapy, with or without denosumab. Radiological response in soft tissue and bone compartments was assessed at 6 months using iRECIST. Disease control (DCR: iCR, iPR, or iSD) and dissociated response (discordant DCR between compartments) were predefined. Denosumab impact was evaluated using logistic regression and Cox models. Results:Sixty-one patients were included (16 women [26%]; mean age 65.8 ± 9.6 years). Soft tissue DCR was 64% and bone DCR was 62% at M6. Dissociated response occurred in 21% (n = 13), associated with female sex, KRAS mutations, and elevated C-reactive protein (all p < 0.05). Denosumab did not alter bone DCR (73% vs. 60%; adjusted OR 0.64; 95% CI: 0.12-2.99; p = 0.582) but was associated with improved progression-free survival (log-rank p = 0.06) and reduced hazard of progression or death (adjusted HR 0.28; 95% CI: 0.06-1.33; p = 0.110). Conclusion:ICI-driven immune activation does not translate uniformly across compartments. Female sex, KRAS mutation, and systemic inflammation are potential determinants of bone-specific resistance. While denosumab did not significantly modify bone DCR, its trend toward association with improved progression-free survival and reduced risk of progression or death generates the hypothesis of an immunomodulatory effect warranting prospective evaluation.
Background:Reconstruction of diaphyseal bone defects of the lower limb after oncologic resection in children remains a major challenge. Several biological techniques are used, including the induced membrane technique (IMT), vascularized fibular graft (VFG), and combined allograft with vascularized fibula graft (CAVFG), but comparative data in pediatric populations remain limited. Questions/purposes:We asked: (1) What are the consolidation outcomes after biological reconstruction of pediatric lower-limb diaphyseal defects? (2) Which factors are associated with time to bone union? (3) What are the complication and revision profiles of these reconstruction strategies? Methods:We conducted a national multicenter retrospective study including pediatric patients (<18 years) who underwent diaphyseal resection of the femur or tibia for malignant bone tumors or adamantinoma between 2004 and 2024. Patients were reconstructed using IMT, VFG, or CAVFG. The primary endpoint was radiographic consolidation at 1 year. Secondary outcomes included overall union rate, time to union, complications, and revision surgery. Time-to-event analyses were performed using Kaplan-Meier and Cox regression models. Results:A total of 133 patients were included (IMT 69, VFG 22, CAVFG 42). Overall bone union was achieved in 72.9% of patients, with no significant difference between reconstruction techniques (IMT 75.4%, VFG 81.8%, CAVFG 64.3%; p = 0.272). Consolidation at 1 year, estimated by Kaplan-Meier analysis, occurred in 35.2% of cases. Median time to union was 18 months and did not differ significantly between techniques. Tibial localization was independently associated with higher union rates (OR 3.90, 95% CI 1.19-12.8; p = 0.024) and shorter time to union (HR 1.89, 95% CI 1.06-3.38; p = 0.032). Complications occurred in 64.1% of patients and 57% required revision surgery, without differences between techniques. Conclusion:Biological reconstruction of pediatric lower-limb diaphyseal defects allows limb salvage with acceptable union rates but prolonged healing and high complication rates. No technique demonstrated clear superiority, supporting an individualized reconstruction strategy based primarily on anatomical and mechanical considerations.
Background:Bone health plays a critical role in prostate cancer irrespective of metastatic status at diagnosis. Preptin, a peptide hormone co-secreted with insulin, exerts osteoanabolic effects and may influence tumor-related processes through insulin/IGF-related signaling pathways. However, its role in the development of bone metastasis remains unclear. This study aimed to evaluate the association between serum preptin levels and bone metastasis in newly diagnosed prostate cancer patients. Methods:This prospective exploratory biomarker study included patients with newly diagnosed prostate cancer. Patients with testosterone levels <25 ng/dL, diabetes mellitus, or unreliable preptin measurements were excluded. Serum preptin levels were measured using enzyme-linked immunosorbent assay (ELISA). Bone metastatic status was determined using 68Ga-PSMA PET/CT findings. Clinical and biochemical parameters were compared between patients with and without bone metastasis. Statistical analyses were performed according to data distribution, with p < 0.05 considered statistically significant. Results:Fifty patients were included, of whom 23 had bone metastasis and 27 did not. Median age was similar between groups (68.9 vs 69.7 years, p = 0.734). Baseline prostate-specific antigen levels were significantly higher in patients with bone metastasis (p < 0.001). Serum preptin levels were comparable between groups (388.6 vs 399.6 ng/L, p = 0.763). Receiver operating characteristic analysis demonstrated no meaningful discriminatory performance of serum preptin for identifying bone metastasis (AUC = 0.525, 95% CI 0.357-0.693, p = 0.763). Conclusion:Serum preptin levels were not associated with bone metastasis in newly diagnosed prostate cancer patients. These findings suggest that circulating preptin may not adequately reflect tumor-bone microenvironment interactions, highlighting the limitations of systemic biomarkers in metastatic processes. Larger longitudinal and tissue-level studies are needed to clarify the biological and clinical relevance of preptin in prostate cancer.
Bone metastasis is a major cause of morbidity and poor survival in solid tumors, yet its progression is often recognized only after overt lesion formation. In this review, we propose a circulating tumor cell/disseminated tumor cell (CTC/DTC)-centered temporal framework that conceptualizes bone metastasis as a sequential and selection-driven process linking dissemination, bone-specific homing, DTC establishment, dormancy, and reactivation. We summarize the key cellular and molecular mechanisms governing these transitions, with particular emphasis on tumor cell plasticity, bone marrow niche interactions, and the dormancy-reactivation interface. We further discuss the translational relevance of this approach for risk stratification, minimal residual disease assessment, treatment monitoring, and emerging experimental strategies, including single-cell multi-omics, spatial omics and biomimetic bone microenvironment models. This perspective shifts the view of bone metastasis from a static, imaging-detectable lesion to a time-resolved biological process and highlights potential windows for earlier risk assessment, disease monitoring, and biology-guided intervention.
Introduction:Evidence on fracture incidence among lung cancer (LC) survivors remains limited. We assessed fracture risk in LC survivors who underwent curative-intent surgery, stratified by treatment modality and postoperative time. Methods:This retrospective, population-based cohort study used the Korean National Health Insurance Service database (2009-2022), including LC survivors (n = 33,292) and 1:3 age- and sex-matched controls (n = 99,876). Competing risk analyses were performed with all-cause mortality as a competing risk. Results:LC survivors had an elevated risk of fracture compared with non-cancer controls across the overall follow-up period. Vertebral fracture risk was most pronounced within the first year after surgery (cause-specific hazard ratios [csHRs] 1.81, 95% confidence interval [CI] 1.45-2.26). Hip fracture risk within the first year was similarly directed but did not reach significance in the overall cohort (csHR 1.40, 95% CI 0.98-1.98), whereas it was significantly elevated in the screening subgroup after additional adjustment for health behaviors and body mass index (csHR 1.83, 95% CI 1.11-4.43). During the overall follow-up period, the risk of any fracture was elevated among LC survivors who received chemotherapy (csHR 1.32, 95% CI 1.21-1.45), radiation therapy (csHR 1.78, 95% CI 1.43-2.23), or chemoradiotherapy (csHR 1.73, 95% CI 1.50-1.99), compared with controls. Conclusion:Compared with non-cancer controls, LC survivors had a generally higher risk of fracture at various sites, which varied by time since surgery and by cancer treatment modality. These findings suggest that osteoporosis screening and multimodal fracture prevention strategies should be considered for LC survivors.
Primary malignant bone tumors (PMBTs) are rare neoplasms arising from bone tissue. Limited evidence suggests an association between reduced serum 25(OH) vitamin D3 levels and PMBT incidence. The active metabolite 1,25(OH)2 vitamin D3 (1,25D3) modulates tumor cell proliferation, apoptosis, and migration through interactions with the vitamin D receptor (VDR). This study investigated the effects of 1,25D3 on osteosarcoma (MG-63, SaOS-2), chondrosarcoma (SW-1353), and Ewing's sarcoma (RD-ES) cell lines. Expression of key components of vitamin D metabolism, including 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), VDR, protein disulfide-isomerase A3 (PDIA3), and the 1,25D3-responsive bone gamma-carboxyglutamate protein (BGLAP), was analyzed at mRNA and protein levels. VDR nuclear translocation was assessed by Western blotting. Cell viability, cell cycle progression, apoptosis, and migration were evaluated using metabolic assays, flow cytometry, immunocytochemistry, wound healing, and live-cell imaging. Treatment with 1,25D3 upregulated CYP24A1 in osteosarcoma cells, while BGLAP expression was detected in both osteosarcoma and SW-1353 cells. All examined cell lines expressed VDR and PDIA3, and 1,25D3 induced VDR nuclear translocation. MG-63 cell viability decreased by 23%, whereas SW-1353 cell viability decreased by 10%, with no significant changes observed in SaOS-2 and RD-ES cells. In MG-63 cells, 1,25D3 induced a significant accumulation of cells in the G1 phase, consistent with cell-cycle arrest, whereas only minor cell-cycle alterations were observed in the other cell lines. Interestingly, 1,25D3 reduced the proportion of apoptotic osteosarcoma cells by 18-30%. The migration of MG-63 cells was significantly reduced by 1,25D3, and an inhibitory trend, albeit not statistically significant, was also observed in RD-ES cells. In conclusion, 1,25D3 modulated cell viability, apoptosis, and migration in PMBT cell models, with distinct, cell-type-specific responses. These findings suggest a potential role for 1,25D3 in regulating PMBT growth and invasiveness.
Background:Chondrosarcomas are malignant cartilage-forming bone tumors with limited therapeutic options, as surgical resection remains the only curative treatment, while chemo- and radiotherapy show limited efficacy due to intrinsic resistance mechanisms. Dysregulation of the Hippo signaling pathway been associated with tumor progression and therapy resistance and has emerged as a promising experimental target across several cancer entities. However, its relevance in chondrosarcoma remains unclear, particularly with regard to potential radiosensitizing effects. Methods:Human chondrosarcoma (SW-1353 and Cal78) and healthy chondrocyte (HC) spheroids were treated with Verteporfin (VP) alone or in combination with X-ray irradiation. Cell viability, Hippo/YAP-TAZ signaling, autophagy-associated markers, DNA damage, apoptosis, ultrastructural alterations, and gene expression were analyzed using ATP assays, immunoblotting, RT-qPCR, immunohistochemistry, and transmission electron microscopy. Results:VP treatment caused a dose-dependent decline in cell proliferation and suppressed key YAP/TAZ target genes, both in chondrosarcoma cells and HC, alongside downregulation of Hippo pathway components and proliferative markers like cMyc and PCNA. Combined with X-ray irradiation, these effects were amplified, supporting a potential radiosensitizing activity of VP in this preclinical model. Ultrastructural and molecular data showed that VP disrupted autophagic balance in all cell types, leading to mitochondrial damage, lipid accumulation, and nuclear fragmentation. Despite the higher basal autophagy in HC cells, VP led to cell death involving autophagy, apoptosis, and DNA damage, evidenced by increased LC3B-II, Beclin, γH2AX, and PARP cleavage. Enhanced DNA damage markers and altered p53-MDM2 signaling after treatment reflect the genotoxic stress induced. Conclusion:Our data suggest that VP, particularly in combination with irradiation, is associated with disruption of multiple survival pathways in chondrosarcoma cells, offering a promising avenue for therapeutic intervention. Future studies should investigate the interplay between autophagy, apoptosis, and Hippo signaling to enable their therapeutic targeting in cancer.
Purpose:Bone metastases are common in patients with metastatic neuroendocrine neoplasms (NENs) and frequently result in skeletal complications. The current role of anti-resorptive agents for these patients is not known. Methods:A systematic review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a PICOS framework searching the Embase, Medline, PubMed, Google Scholar, Cochrane library and Web of Science databases to identify studies reporting the use of anti-resorptive agents in patients with well-differentiated NENs who have bone metastases. Results:A total of 2424 articles were identified with 104 selected for full text review. After review, five retrospective studies were included in the review. Study design was heterogenous, and treatment details typically poorly described. A total of 348 patients were included in the review, of whom 206 received anti-resorptive treatment. One study (N = 19) reported an increase in overall survival with use of monthly bisphosphonates whereas no difference in survival with use of anti-resorptive agents were identified in three studies. The response to anti-resorptive therapy was positively associated with overall survival in one study. One study reported a significant reduction in SRE in the group receiving anti-resorptive therapy. Significant toxicity from anti-resorptive therapy was reported in 15.2% of patients in one study whereas treatment complications were not documented in the other three studies. Conclusion:Currently, there are insufficient data as to the role of anti-resorptive agents in patients with NENs and a prospective trial is needed.
Centromere-associated genes are linked to genomic instability and tumor progression, yet their significance and immunological roles in osteosarcoma (OS) remain undefined. Methods: We developed a centromere-associated prognostic gene model (CPGM) by applying machine learning across independent cohorts, including TARGET-OS and GEO databases. The Meta-OS and GEO datasets were integrated to form a comprehensive Meta-OS cohort for further analysis. Model performance was evaluated using Harrell's concordance index (C-index). Then, the optimal model was selected and validated using Kaplan-Meier plotter, time-dependent ROC (tROC), Cox regression, and nomogram construction. Functional enrichment and immune infiltration analyses were performed to characterize the tumor immune microenvironment. Single-cell RNA sequencing (scRNA-seq) was conducted to assess cellular heterogeneity and intercellular communication. Finally, the function of Beta-1,3-galactosyltransferase 4 (B3GALT4) was validated using in vitro assays to evaluate its effects on OS cell proliferation and migration. Results: The CPGM demonstrated consistent prognostic performance across independent datasets, achieving a maximum C-index at 0.733. The tROC analysis showed strong predictive accuracy, with area under of curve values of 0.857, 0.806, and 0.783 at 1, 3, and 5 years, respectively. Univariate and multivariate Cox analyses confirmed CPGM as an independent prognostic factor (p = 0.002). Meanwhile, high CPGM scores were associated with poor survival, higher tumor purity, reduced immune infiltration, and suppressed antitumor immune responses. Enrichment analyses indicated significant involvement of immune-related pathways. scRNA-seq analysis revealed that high-CPGM cells were enriched in early developmental trajectories and exhibited enhanced intercellular signaling. Among the model genes, B3GALT4 was consistently downregulated in OS tissues and cell lines, and low expression correlated with poor prognosis. Overexpression of B3GALT4 significantly inhibited the proliferation, migration and invasion of OS cells. Conclusion: This study establishes a robust centromere-associated prognostic model linked to immune dysregulation in OS and identifies B3GALT4 as a potential tumor suppressor and therapeutic target.
Background:Bone pain affects up to 80% of patients with multiple myeloma (MM) patients and significantly impairs quality of life (QoL), yet its specific predictors remain poorly characterized. Identifying risk factors is essential for early intervention and personalized treatment. Methods:This prospective, single-center study included 352 patients. Bone pain was recorded using a standardized questionnaire. Multivariate logistic regression with stepwise selection was used to identify independent predictors of bone pain. QoL and health-related status were assessed on a 7-point scale and compared using the Wilcoxon two-sample test. Results:Bone pain was reported by 184 patients (52%). Independent predictors of bone pain were osteolytic lesions with fracture risk (OR 3.06, 95% CI 1.46-6.40, p = 0.003) and pre-existing orthopedic disease (OR 2.78, 95% CI 1.77-4.36; p < 0.0001). CRAB (hypercalcemia, renal failure, anemia, bone lesions)-B at initial diagnosis (OR 1.74, 95% CI 0.92-3.29, p = 0.09) and progressive disease (OR 1.68, 95% CI 0.93-3.05, p = 0.09) showed an elevated risk for bone pain. No associations were observed for age, sex, CRAB-C/-R/-A, International Staging System (ISS) stage, and disease duration after adjustment. Patients with bone pain had significantly lower median QoL and health-related status compared to patients without pain (p < 0.001). Conclusions:Osteolytic lesions with fracture risk and pre-existing orthopedic conditions independently predict bone pain in patients with MM. These findings highlight the different etiology and the overlap between orthopedic and oncological conditions. Interdisciplinary management is essential to distinguish MM-caused pain from degenerative pain and optimize individualized care.
Background:Megaprostheses may contain multiple modular junctions and, depending on implant design, specific coupling or hinge mechanisms that can contribute to fretting, wear, corrosion, and systemic metal ion release. This systematic review evaluated blood metal ion levels in patients undergoing limb-salvage oncologic surgery with a megaprosthesis. Material and methods:A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and Web of Science were searched from inception to September 16, 2024. Studies were eligible if they reported metal ion levels after upper or lower oncologic megaprosthesis reconstruction. Data were extracted for cobalt, chromium, titanium, aluminium, molybdenum, and silver at prespecified postoperative intervals (0-2 months, 2-12 months, and > 12 months), together with study and patient characteristics, anatomical location/reconstruction type, and reported complications. Data were summarized using arithmetic means and sample-size-weighted means. Results:Thirteen studies comprising 16 cohorts and 247 patients were included. Blood cobalt, chromium, and titanium concentrations were higher in later postoperative intervals. At >12 months, mean cobalt, chromium, and titanium concentrations were 8.2 ppb, 4.2 ppb, and 8.1 ppb, respectively; upper-quartile values reached 21.1 ppb for cobalt, 11.7 ppb for chromium, and 9.6 ppb for titanium. Silver concentrations were 8.2, 2.9, and 9.2 ppb at 0-2, 2-12, and > 12 months, respectively, whereas aluminium and molybdenum were only reported beyond 12 months, with mean values of 7.8 and 0.5 ppb. No included study consistently linked elevated ion levels with systematically assessed ARMD, pseudotumor formation, renal failure, or cardiac toxicity. Conclusion:Blood cobalt, chromium, and titanium concentrations appeared higher in later postoperative intervals after oncologic limb-salvage reconstruction with megaprostheses. Some patients may exceed commonly cited thresholds, particularly for cobalt, but the clinical significance remains uncertain because relevant outcomes were inconsistently assessed.
Objective:This review systematically evaluates the current research landscape, methodological characteristics, and translational challenges of artificial intelligence (AI) integrated with magnetic resonance imaging (MRI) across the diagnostic and therapeutic pathway of spinal metastases, with the aim of informing clinical practice and future research. Methods:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search of PubMed, Web of Science, and the Cochrane Library. Original studies investigating AI models, including machine learning, deep learning, and large language models, developed from MRI data for spinal metastases were included. Two reviewers independently screened studies and extracted data. Sixty-one studies were included in the qualitative synthesis. Results:The included studies focused on four core clinical tasks: diagnosis and pathological classification (23 studies), clinical prognosis and risk stratification (17 studies), lesion detection and segmentation (16 studies), and automated clinical scoring and report analysis (5 studies). AI models showed promising performance across these tasks, with the highest area under the curve (AUC) for benign-malignant differentiation reaching 0.98 and the highest Dice similarity coefficient (DSC) for automatic lesion segmentation exceeding 0.85. Nevertheless, important limitations remain. Most studies were single-center retrospective investigations (73%), and the majority addressed isolated tasks rather than integrated clinical workflows. Important gaps also persist in multicenter generalizability, long-term survival prediction, and multimodal data integration. Conclusion:MRI-based AI has substantial potential to improve the diagnosis and management of spinal metastases. Future studies should emphasize large-scale, multi-center prospective validation and integrated intelligent systems supporting screening, decision-making, treatment response assessment, and long-term follow-up.
Objective:To investigate the clinical value of urinary N-telopeptide (NTx) of type I collagen in diagnosing bone metastasis (BM) from lung cancer and to optimize a multi-indicator combined detection strategy. Methods:The study enrolled patients from a healthy control group, a lung cancer without bone metastases (LC-nonBM) group, and a lung cancer with bone metastases (LC-BM) group. The diagnostic performance of NTx-to-creatinine ratio (NTx/Cr) was evaluated by comparing biochemical indicators, staging characteristics, and receiver operating characteristic (ROC) curve analysis. Results:NTx/Cr showed statistically significant differences across various stages within the LC-nonBM group (P = 0.004). In the LC-BM group, NTx/Cr levels were significantly elevated (P < 0.001) and positively correlated with the number of bone metastatic lesions. ROC curve analysis revealed that NTx/Cr alone achieved an areas under the curve (AUC) of 0.78 for diagnosing bone metastasis, while the three-indicator combination of the urinary NTx/Cr, serum alkaline phosphatase (ALP), and calcium (Ca) reached an AUC of 0.882, indicating a marked improvement in diagnostic performance. Conclusion:Urinary NTx/Cr is an effective biomarker for diagnosing bone metastasis in lung cancer, and its level is closely associated with tumor stage and metastatic burden. A multi-indicator diagnostic model combining NTx/Cr, ALP, and Ca significantly enhances diagnostic accuracy.
Endoprosthetic reconstruction of the proximal femur is a well-accepted technique in the treatment of bone tumours. However, controversies remain regarding the optimal reconstructive technique. For instance, there is little evidence to support resurfacing of the acetabulum. Our preferred technique during recent years was hemiarthroplasty with a bipolar femoral head and an attachment tube for tendinous reinsertion. Aim of this study was to evaluate the long-term clinical outcomes of these reconstructions. All consecutive patients in whom a MUTARS® proximal femoral replacement was performed between 1999 and 2023 for a primary bone tumour were retrospectively evaluated, with a minimum follow-up of 24 months. Sixty-four patients matched inclusion criteria. Mean age was 52 years (8 to 89). Chondrosarcoma was the predominant diagnosis (n = 37, 58%), followed by osteosarcoma (n = 16, 25%). At review, 36 patients (56%) were alive. Median follow-up was 10.1 years (IQR 4.5-14.7). Fifty-four reconstructions (84%) were bipolar hemiarthroplasties. Twenty-eight (44%) implants were silver-coated. Median reconstruction length was 18 cm (8 to 45). Dislocation occurred in five bipolar hemiarthroplasties (9%) and in three total hip arthroplasties (33%). Aseptic loosening was not observed. One periprosthetic fracture was observed (2%). Deep infections occurred in eight reconstructions (13%). The cumulative incidence of mechanical failure at five, ten, and fifteen years was 11.8% (95% CI 3.4-20.3), 22.6% (95% CI 10.1-35.2), and 29.7% (95% CI 14.4-44.9). In our experience, bipolar hemiarthroplasty appears to be a viable technique for reconstruction of the proximal femur after bone tumour resection, with a low rate of mechanical failure and acetabular wear at long-term follow-up.
Background:Chondrosarcoma (CHS) is the second most common primary malignant bone tumor and remains resistant to conventional therapies, underscoring the need to discover novel therapeutic targets. Cancer/testis antigens (CTAs), a class of tumor-associated proteins, represent attractive antigens for cancer immunotherapies such as adoptive T cell therapy. However, the expression profile of CTAs and their associated targetable immunopeptides presented in the Human Leukocyte Antigen-I context (pHLA) remain unknown in CHS. This study aims to characterize the CTA expression profile according to the tumor immune phenotype and clinical outcomes, and to identify the most relevant pHLA to target in CHS. Method:We analyzed the CTA expression profile in tumors from 63 conventional CHS patients and in healthy tissues using GTEx and HPA databases to identify CHS-associated CTAs. Cox proportional hazards models combined with hierarchical clustering were used to correlate CTA expression with the overall survival of patients. The tumor immune phenotype was estimated based on immune gene expression signatures using a deconvolution method and a Pearson correlation coefficient matrix. The CTA-derived pHLA were characterized using immunopeptidomic profiling based on HLA-I immunoprecipitation and mass spectrometry in grade 2 and 3 CHS models. NetMHC was used to predict the binding affinity of identified pHLA to the HLA-A*02:01 and HLA-A*01:01 alleles. Results:We identified a poor prognosis CTA signature predominantly associated with a non-inflamed tumor immunophenotype. Immunopeptidomic profiling revealed broad pHLA repertoires, including previously well-characterized CTAs from PRAME, CTAG2 and the MAGE-A family, as well as newly identified candidates with strong predicted HLA-binding affinity from CTAs such as HHIPL2, DBF4, BRIP1, CBX2 and DIAPH3. Conclusion:This study provides the first atlas of pHLA in CHS and suggests specific antigenic targets for TCR-T cell therapies and targeted therapies such as antibody-drug conjugates.
Osteosarcoma (OS) is an aggressive primary bone malignancy with poor prognosis for metastatic and recurrent cases, highlighting an urgent need for novel therapeutic strategies. The human cathelicidin peptide LL-37 exerts context-dependent anti-tumor effects, yet its functional role in OS remains largely undefined. This study aimed to explore the anti-OS activity and underlying mechanisms of LL-37. METHODS:In vitro experiments were performed using OS cell lines and normal human bone marrow mesenchymal stem cells (hBMSCs) to assess cell viability, clonogenic survival, migration, invasion, cell cycle distribution, cell death, and cholesterol metabolism. Transcriptomic profiling, siRNA-mediated knockdown, plasmid overexpression, and rescue experiments were conducted to validate key signaling pathways. The in vivo therapeutic efficacy of LL-37 was evaluated using a 143B cell xenograft model. RESULTS:LL-37 selectively inhibited the viability of OS cells with minimal toxicity to hBMSCs. It significantly suppressed clonogenic survival, migration, and invasion, induced S-phase cell cycle arrest, and triggered both mitochondrial apoptosis and caspase-1/GSDMD-dependent pyroptosis. Transcriptomic analysis identified cholesterol biosynthesis as a key pathway downregulated by LL-37, with the rate-limiting enzyme squalene epoxidase (SQLE) markedly reduced. Mechanistically, LL-37 upregulated the tumor suppressor PTEN, thereby inhibiting the AKT/mTOR pathway and suppressing SREBP2/SQLE-mediated cholesterol synthesis. Rescue experiments confirmed that SQLE inhibition was required for the pro-apoptotic effects of LL-37. In vivo, LL-37 dose-dependently inhibited the growth of OS xenografts with efficacy comparable to cisplatin, without causing obvious systemic toxicity. CONCLUSION:LL-37 exerts anti-OS effects by targeting the PTEN/AKT/mTOR-SREBP2/SQLE axis to suppress cholesterol synthesis and induce dual cell death. It represents a promising and selective candidate, providing a theoretical basis for cholesterol metabolism-targeted therapy in osteosarcoma.
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder characterized by an insidious onset, while its underlying pathogenesis has not yet been fully explored. Identifying and accurately localizing the causative tumors in TIO remains highly challenging in clinical practice. Although complete surgical excision following precise diagnosis is currently considered the most effective treatment approach, surgical management strategies still require optimization, and recurrence may occur even after tumor resection. TIO is primarily recognized as a metabolic bone disease driven by excessive secretion of fibroblast growth factor 23 (FGF23) by tumors; however, its detailed etiological features and molecular pathogenic mechanisms remain unclear. Besides FGF23, other phosphate-regulating hormones and pathogenic genes are also believed to participate in disease development. A clearer understanding of FGF23-mediated phosphate regulation, including hormone secretion, circulation, transport, and interactions with target organs, is critical for early diagnosis and the development of effective therapeutic strategies. Further investigation into the mechanisms responsible for refractory and recurrent TIO is also needed. Integrated multi-omics approaches are expected to provide deeper insight into the complex pathogenic basis of TIO, supporting the development of improved diagnostic and therapeutic strategies. This review summarizes recent progress in understanding the etiology and pathogenesis of TIO, intending to improve disease comprehension and facilitate more effective clinical diagnosis and treatment.
