Calcified Tissue International最新文献

{"title":"Associations between controlling nutritional status and mortality in osteoporosis: evidence from NHANES, 2005-2018.","authors":"Min-Hong Hsieh, Chang-Chen Yang, Ching-Hsing Lin, Wen-Yan Lin, Huan-Ming Tang, Chun-Hsi Huang, Yen-Sheng Chiang, Po-Hsun Lin, Hung-Yang Chien, Yan-Jyun Chen, Keng-Chang Liu, Jui-Teng Chien","doi":"10.1007/s00223-026-01565-z","DOIUrl":"10.1007/s00223-026-01565-z","url":null,"abstract":"<p><p>Malnutrition and immune dysregulation are common in patients with osteoporosis but are often overlooked and may contribute to poor outcomes. The Controlling Nutritional Status (CONUT) score is a simple instrument reflecting both nutritional and immune status, but its prognostic value in osteoporosis remains unclear. This retrospective, observational study included data of adults aged ≥ 50 years with osteoporosis extracted from five two-year cycles of the National Health and Nutrition Examination Survey (NHANES; 2005-2006, 2007-2008, 2009-2010, 2013-2014, and 2017-2018). Osteoporosis was defined as femoral neck T-score < - 2.5. CONUT scores were calculated from participants' serum albumin, total cholesterol, and total lymphocyte count, and high CONUT was defined as ≥ 2. All-cause and cardiovascular disease (CVD)-related mortality through December 31, 2019, was ascertained via the National Death Index. Weighted Cox regression models were used to estimate hazard ratios (HRs) for mortality outcomes. Among 871 participants representing 5.86 million US adults with osteoporosis, 40.7% had high CONUT scores. During a median follow-up of 9.8 years, high CONUT scores were associated with increased all-cause mortality (53.2% vs. 30.9%, p < 0.001) and CVD mortality (17.6% vs. 8.2%, p < 0.001). In multivariable analysis, after adjustments for possible confounders, high CONUT scores were independently associated with higher all-cause (HR 1.64; 95% CI 1.25-2.14) and CVD mortality (HR 1.91; 95% CI 1.15-3.19). Associations with all-cause mortality were consistent across sex, diabetes, and CKD subgroups and associations with CVD mortality were most pronounced among females and patients with diabetes. The CONUT scores may help identify high-risk individuals, particularly those with greater comorbidity burden, who may benefit from closer monitoring and more comprehensive nutritional assessment.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota-Derived TMAO Drives MC3T3-E1 Senescence and Osteogenic Dysfunction via cGAS-STING-NF-κB Signaling: Implications for Age-Related Bone Loss.","authors":"Lingling Li, Xinsai Li, Mingming Jin, Yangyang Zhang, Jia Bai, Jinyang An, Ying Yang, Shuyun Li, Haihong Lv","doi":"10.1007/s00223-026-01567-x","DOIUrl":"https://doi.org/10.1007/s00223-026-01567-x","url":null,"abstract":"<p><p>Age-related osteoporosis is closely associated with osteoblast dysfunction, in which cellular senescence plays a key role. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, is implicated in aging and metabolic diseases and has been linked to bone metabolism. However, whether TMAO impairs bone formation by regulating osteoblast senescence remains unclear. This study investigated the effects of TMAO on osteoblast senescence and osteogenic function, focusing on the cGAS-STING-NF-κB signaling axis. MC3T3-E1 cells were treated with TMAO to evaluate proliferation, cell cycle progression, senescence, and osteogenic differentiation. Cytosolic DNA release and activation of the cGAS-STING-NF-κB axis were assessed. In vivo, a chronic TMAO exposure model was established, combined with AAV9-mediated STING knockdown, and bone microarchitecture was analyzed by micro-CT. TMAO significantly inhibited proliferation and induced G0/G1 arrest in MC3T3-E1 cells without apparent cytotoxicity. It increased SA-β-gal-positive cells and upregulated senescence-associated markers, indicating a senescent phenotype. Functionally, TMAO suppressed osteogenic differentiation and mineralization and downregulated osteogenic proteins. Mechanistically, TMAO promoted abnormal release of mitochondrial DNA into the cytosol, activated the cGAS-STING pathway, and enhanced NF-κB signaling. STING overexpression exacerbated, whereas STING knockdown alleviated, TMAO-induced senescence and osteogenic impairment. NF-κB inhibition partially reversed these effects. In vivo, TMAO exposure impaired trabecular and cortical bone microarchitecture, which was partially improved by STING knockdown. TMAO induces osteoblast senescence and impairs osteogenic function, potentially via mtDNA-mediated activation of the cGAS-STING-NF-κB axis. These findings provide insight into age-related bone loss and suggest potential therapeutic targets.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence Approaches for Osteoporotic Fracture Risk Prediction Using Administrative Health Data: A Systematic Review.","authors":"Benjamin Bakke Hansen, Kasper Westphal Leth, Nana Roust Hansen, Bo Abrahamsen, Nicholas Rubek Fuggle, Jan Christian Brønd, Katrine Hass Rubin","doi":"10.1007/s00223-026-01563-1","DOIUrl":"10.1007/s00223-026-01563-1","url":null,"abstract":"<p><p>To systematically review Machine Learning (ML) fracture risk prediction models developed solely using administrative data, evaluating their development, performance, risk of bias, and concerns regarding applicability. A systematic search was conducted in PubMed, Embase, IEEE, and Web of Science following PRISMA guidelines (up to November 2025). We included studies developing or validating ML models for osteoporotic fracture risk in adults using administrative data without clinical measurements. Risk of bias and concerns for applicability were assessed using the PROBAST tool. Seven studies were included from 3435 initial records. A range of of ML models were utilized, including Random Forests, XGBoost, LASSO-regularized Logistic Regression and Neural Networks. Discriminative performance was moderate-to-good, with best Area Under the Curve (AUC) values ranging from 0.818 for osteoporotic fractures in general to 0.905 for hip fractures only. While five studies showed low risk of bias, five raised applicability concerns due to using specific subpopulations or features with database characteristics. Only two studies used external validation and none directly evaluated clinical utility of the models. ML models using solely administrative data show some promise as scalable, automated tools for fracture risk prediction without requiring manual clinical input. However, clinical implementation is hindered by limited external validation and a lack of formal utility evaluation of the models. Future research should prioritize more rigorous external validation and recalibration of the existing models, more so than the development of novel models, ensuring they are robust, interpretable, and integrable into future clinical workflows.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13303480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Important Role of Polycystin in the Skeletal System.","authors":"Jia Zhang, Qiaoli Dai, Qian Chen, Rongkang Mou, Ting Kang, Zuping Wu","doi":"10.1007/s00223-026-01566-y","DOIUrl":"10.1007/s00223-026-01566-y","url":null,"abstract":"<p><p>The polycystin (PC) protein family, including Polycystin-1 (PC1) and Polycystin-2 (PC2), was initially identified for its role in autosomal dominant polycystic kidney disease (ADPKD). Recent studies reveal that these mechanosensitive proteins play significant roles in skeletal development, homeostasis, and disease. PC1 and PC2 participate in mechanotransduction in bone cells and regulate the differentiation and function of osteoblasts, osteoclasts, and other skeletal cells through multiple signaling pathways, thereby influencing bone remodeling. Dysregulation of PC signaling is associated with various skeletal disorders, including osteoporosis, impaired fracture healing, craniosynostosis, and maxillofacial abnormalities. This review summarizes the structure, expression, molecular mechanisms, and clinical significance of polycystins in the skeletal system. We discuss their roles in different bone cell types, the signaling pathways involved, and emerging therapeutic strategies targeting PC-mediated mechanotransduction. Understanding the mechanosensitive functions of polycystins in bone provides a theoretical basis for developing new approaches to prevent and treat skeletal diseases. Further research on mechanisms and therapeutic applications will help elucidate bone metabolism regulation and advance clinical management of related conditions.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of High-Impact Exercise on Bone Marker Concentrations During Controlled Low Energy Availability in Recreational Female Runners.","authors":"Trisha Sterringer, Craig Sale, Anna Morozov, Jiarui Liang, D Enette Larson-Meyer","doi":"10.1007/s00223-026-01564-0","DOIUrl":"10.1007/s00223-026-01564-0","url":null,"abstract":"<p><p>Exposure to low energy availability (LEA) can stimulate metabolic adaptations that have been shown to disrupt bone remodeling as suggested by suppressed markers of bone formation and/or increased markers of bone resorption. Previous studies suggest that brief, high-impact exercise during short-term energy restriction may stimulate an osteogenic response and mitigate the negative effect of LEA on bone health. This randomized, crossover study of twelve recreational female runners (age: 26.4 ± 3.9 years, VO_2max: 45.3 ± 7.2 mL/kg/min) assessed the short-term effects of jumping exercises on markers of bone formation and resorption after five days of experimentally-controlled LEA (15 kcal/kgFFM/d). Participants completed two LEA conditions that involved daily treadmill running with either no additional exercise (RUN) or an additional 50 jump exercises per day (RUN + J). Fasted bone markers and hormone concentrations were measured on the mornings immediately before and after each intervention period. Bone resorption marker β-CTX was increased over time in both LEA conditions (main effect of time: P = 0.005; preRUN: 0.32 ± 0.21, postRUN: 0.36 ± 0.15 ng/mL; preRUN + J: 0.38 ± 0.21, postRUN + J: 0.42 ± 0.19 ng/mL) with no interaction effect (P = 0.716). Bone formation biomarkers, PINP and sclerostin, did not change over time (P = 0.517, P = 0.091) or between conditions (P = 0.187, P = 0.666). In conclusion, performing 50 jumping exercises during short-term LEA did not have an effect on markers of bone resorption or formation during short-term LEA induced by running exercise and dietary energy restriction.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13303319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional model for amelogenesis: polarization and pH sensitivity of calcium uptake in ameloblast-derived HAT-7 cells.","authors":"Kristóf Kádár, Anna Földes, Róbert Rácz, Susan Van-Weert, Ádám Soós, Jason Bruce, Martin C Steward, Pamela DenBesten, Gábor Varga, Ákos Zsembery","doi":"10.1007/s00223-026-01559-x","DOIUrl":"10.1007/s00223-026-01559-x","url":null,"abstract":"<p><p>Enamel mineralization requires calcium (Ca²⁺) entering the matrix through the epithelium. The exact transepithelial Ca²⁺ transport process remains unclear. We have previously shown that rat-derived HAT-7 ameloblast cells, cultured in a polarized condition, achieve transepithelial bicarbonate transport. Our current aim was to determine the functional polarization of known amelogenesis-related Ca²⁺ transporters and channels in polarized HAT-7 cells. HAT-7 cells were cultured on Transwell membranes. The formation of a confluent monolayer was monitored by measuring transepithelial resistance. Relative mRNA expression of calcium channels was compared using TaqMan qPCR assays. Intracellular Ca²⁺ responses were followed by ratiometric Ca²⁺-imaging (fura-2 AM). Store-operated Ca²⁺ entry (SOCE) was activated by store depletion, using the SERCA inhibitor thapsigargin, while TRPM7 function was evaluated using the agonists naltriben and mibefradil. Functional polarization was determined by separate perfusion of the apical and basolateral membrane domains. The effects of both apical and basolateral extracellular acidification on calcium transport were also assessed. HAT-7 cells exhibited high Trpm7 mRNA expression, although much of the TRPM7 protein was localised to intracellular organelles. mRNAs for the SOCE channels Orai1, Orai2 and Orai3 were also detected. Both SOCE and TRPM7 activity showed functional polarization: SOCE being more prominent on the basolateral side while the TRPM7 activity was predominantly observed apically. Basolateral but not apical extracellular acidification reduced the basolateral SOCE-related Ca²⁺ entry. In summary, Ca²⁺ uptake mechanisms showed significant functional polarization in confluent HAT-7 monolayers, suggesting that HAT-7 cells may provide a model for transepithelial Ca²⁺ transport during enamel maturation.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMAL1 Proteostasis, Circadian Dysfunction, and Ferroptotic Vulnerability in Osteoporosis: Current Evidence and Experimental Priorities.","authors":"Xiping Dou, Jiangying Zhang, Yixiang Zhao, Haochuan You, Xiuyuan Wang, Yayi Xia","doi":"10.1007/s00223-026-01560-4","DOIUrl":"10.1007/s00223-026-01560-4","url":null,"abstract":"<p><p>Osteoporosis is increasingly recognized as a disorder of impaired skeletal adaptation in which endocrine stress, metabolic injury, altered mechanotransduction, remodeling imbalance, and redox vulnerability converge. Bone is also a circadian tissue, and ferroptosis is now directly implicated in skeletal cell dysfunction across several osteoporosis-related settings. This review examines whether proteostatic instability of brain and muscle ARNT-like 1 (BMAL1) could represent a mechanistically relevant link between these processes. To keep interpretation proportionate to the available data, bone-established evidence is distinguished from extra-skeletal bridge mechanisms and disease-contextual extrapolations that remain unproven in bone. Current evidence supports three conclusions. First, circadian regulation in bone extends beyond BMAL1 transcript abundance and must be interpreted within the broader clock network. Second, ferroptosis is directly established in osteoblasts and osteocytes across postmenopausal, glucocorticoid-related, diabetic, iron-overload, and unloading-related contexts. Third, BMAL1 is functionally important for skeletal differentiation and stress adaptation, but selective BMAL1 degradation and clockophagy have not yet been demonstrated in skeletal cells. Taken together, the literature does not justify describing clockophagy as an established skeletal pathway, but it does support a testable framework for defining when BMAL1 proteostasis may become pathogenic in osteoporosis and which experiments could most decisively validate or refute that possibility.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parathyroid Hormone Related Peptide (PTHrP) Revisited: A Comparison of Levels in Malignant and Non-malignant Conditions.","authors":"Guoyu Ling, Rukayat Akande, Stewart G Albert","doi":"10.1007/s00223-026-01552-4","DOIUrl":"10.1007/s00223-026-01552-4","url":null,"abstract":"<p><p>Elevated parathyroid hormone-related peptide (PTHrP) levels are often presumed to indicate malignancy-associated hypercalcemia, yet PTHrP may be elevated in nonmalignant conditions. We compared PTHrP levels in patients with known malignancies with patients with elevations of PTHrP who had defined nonmalignant diagnoses to determine which levels of PTHrP were more indicative of malignancy. A retrospective review of electronic medical records in a large midwestern hospital system was conducted using search terms hypercalcemia with elevated PTHrP (> 2.3 pmol/L (men) and > 3.4 pmol/L (women). Binary logistic regression analyses assessed the positive predictive value (PPV, probability) of cancer. Among 236 patients with hypercalcemia and elevated PTHrP, 58 had known cancer. The others had defined nonmalignant diagnoses including primary hyperparathyroidism (n = 87), absorptive hypercalcemia (n = 28), and \"other\" causes (n = 63). PTHrP was highest in the cancer group (PTHrP = 36.9, 95% CI 19.8, 53.9 pmol/L, p < 0.001), however, overlap occurred. Binary logistic regression analyses showed a positive association of PTHrP levels (p < 0.001), while PTH levels were negatively associated (p < 0.001) with the presence of cancer. When analyzed together, PTH on PTHrP had independent effects (p < 0.001). At PTH ≥ 30 pg/mL, the PPV of cancer was < 5% when PTHrP < 7.0 pmol/L and < 10% at a PTHrP < 9.0 pmol/L. In the evaluation of hypercalcemia with elevated PTHrP, simultaneous levels of PTH measurements improve estimation of cancer probability. Mild PTHrP elevations with PTH > 30 pg/mL are more consistent with nonmalignant diagnoses, although higher PTHrP levels may still warrant evaluation for occult malignancy.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial \"Enamel\" Issue.","authors":"Sylvie Babajko, Catherine Chaussain, Stefan Habelitz, Rodrigo S Lacruz","doi":"10.1007/s00223-026-01561-3","DOIUrl":"https://doi.org/10.1007/s00223-026-01561-3","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiscale mechano-biological characterization of necrotic, sclerotic, and healthy zones in femoral head osteonecrosis: linking viscoelastic heterogeneity to mechanical failure.","authors":"Ajeesh M Kurup, Rajesh Kumar Bhushan, Saroj Kumar, Amit Kumar, Naveen Kumar, Ramesh Kumar Sen, Navin Kumar","doi":"10.1007/s00223-026-01557-z","DOIUrl":"10.1007/s00223-026-01557-z","url":null,"abstract":"<p><p>Osteonecrosis of the femoral head (ONFH) is a progressive disorder characterized by regional trabecular bone deterioration that ultimately results in collapse. While elastic property changes in diseased bones are well documented, the contribution of region-specific viscoelastic behavior and its relationship to multiscale microarchitecture and composition remain insufficiently defined. Eighteen femoral heads (mean age: 40.8 ± 7.1 years; 15 males, 3 females; diagnosis: Ficat Stage III/IV) were retrieved during total hip arthroplasty. Patient-matched trabecular cores were harvested from three distinct zones: necrotic (NCZ), sclerotic (SCZ), and healthy (HZ). Bone quality was evaluated using micro-CT, uniaxial compression, nanoindentation, FTIR, and XRD. Viscoelasticity was characterized via stress relaxation and dynamic mechanical analysis (DMA) tests. The NCZ demonstrated microarchitectural decay (bone volume/total volume reduced by 54.54%, p < 0.001) and lower elastic modulus (reduced by 60.25%, p < 0.001) compared to SCZ. DMA revealed that while the NCZ exhibited the lowest storage modulus (E^'), it showed a trend toward greater matrix-dominated stress relaxation (~ 25% increase). Conversely, the SCZ exhibited a 60% increase in E^' (p < 0.01) but significantly reduced damping and post-yield energy than NCZ, consistent with a stiff yet brittle phenotype. Stress relaxation correlated strongly with mineral/matrix ratio (r = - 0.71) and collagen maturity (r = - 0.64), with collagen spectral markers significantly predicting microscale mechanical properties. ONFH induces profound viscoelastic and structural heterogeneity. This zonal mismatch between the compliant necrotic core and the stiff, brittle sclerotic rim likely promotes stress concentrations, driving structural instability and subchondral failure.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}