Calcified Tissue International最新文献

{"title":"Examination of Skeletal and Senescence Phenotypes in Young Mice with Juvenile Onset Type 1 Diabetes.","authors":"Japneet Kaur, Hannah W Brooks, Mitchell N Froemming, Nicholas C Cusick, Janet L Funk, Joshua N Farr","doi":"10.1007/s00223-025-01401-w","DOIUrl":"https://doi.org/10.1007/s00223-025-01401-w","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) and T2D are associated with skeletal fragility, contributing to increased fracture risk. Whereas decreased bone mineral density (BMD) is common in T1D, individuals with T2D tend to have normal or elevated BMD. These differences are incompletely understood but may stem from distinct mechanisms. Previously, we showed that obese male C57BL/6 mice (7-month-old) with T2D exhibit poor bone quality and accelerated osteocyte senescence with a unique senescence-associated secretory phenotype (SASP). We hypothesized that, similar to T2D, senescent osteocytes and additional senescent bone-resident cells (e.g., immune cells) accumulate in T1D. Consistent with previous studies, we studied a juvenile onset (2-month-old) T1D model, where following 8 weeks, male C57BL/6 mice with T1D displayed deteriorated bone microarchitecture, increased cortical porosity, and reduced bone strength. Unexpectedly, osteocytes, myeloid cells, T cells, and B cells in T1D mice showed no significant changes in key senescence/SAPS markers. Therefore, although T1D mice display several aspects of poor bone quality, consistent with juvenile-onset T1D in humans, senescent cells have yet to accumulate at substantial levels in bone at this young age. Future studies should include female mice and test whether senescence requires a later onset of T1D, a longer disease duration, or worse glycemic control.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"93"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539094","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":"Feasibility of 100 kV Low-voltage Bone Mineral Density Measurement with Quantitative CT: Phantom and Clinical Research.","authors":"Yali Li, Dan Jin, Yan Zhang, Mengze Zhang, Zhen Qian, Chenyu Jiang, Ming Ni, Suwei Liu, Huishu Yuan","doi":"10.1007/s00223-025-01393-7","DOIUrl":"https://doi.org/10.1007/s00223-025-01393-7","url":null,"abstract":"<p><p>To investigate the feasibility and accuracy of 100 kV low-voltage quantitative CT (QCT) for bone mineral density (BMD) measurement using the European Spine Phantom and patients. The accuracy and precision of the BMD measurements were assessed using relative measurement error (RME%), coefficient of variation (CV%), root mean square standard deviation (RMS-SD), and root mean square CV (RMS-%CV). Linear regression and Bland‒Altman analyses were used to assess the agreement between 100 and 120 kV QCT-based BMD measurements. The diagnostic performance of 100 kV QCT for osteoporosis was evaluated using receiver operating characteristic curve analysis. For the ESP, the mean BMD values at 100 kV were slightly greater than those at 120 kV, mainly due to small inaccuracies remaining in the BMD calibration process. The RME% values for all vertebrae were -3.31 to 15.00% at 100 kV and -9.34 to 3.06% at 120 kV, falling within ± 10% at 120 kV but within 0‒15% at 100 kV. The CV% and RMS-%CV values decreased as the BMD increased with increasing tube voltage, while the RMS-SD exhibited a decreasing trend. For patients, linear regression and Bland‒Altman analyses revealed good agreement between 120 and 100 kV (R² = 0.987, P < 0.001; mean error, -3.39 mg/cm³; 95% limits of agreement, -16.49 to 9.71 mg/cm³). The 100 kV QCT achieved high accuracy in diagnosing osteoporosis (AUC = 0.992, P < 0.001), with a sensitivity of 99.04% and a specificity of 94.28%. 100 kV low-voltage QCT demonstrated acceptable accuracy and good reproducibility for measuring BMD, opening the possibility of 100 kV low-voltage chest CT obtained for lung cancer screening for opportunistic osteoporosis screening.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"92"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539095","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":"Differential diagnosis of heritable and acquired osteomalacia in children: biochemical and biomaterial signatures.","authors":"Suma Uday, Wolfgang Högler","doi":"10.1007/s00223-025-01398-2","DOIUrl":"https://doi.org/10.1007/s00223-025-01398-2","url":null,"abstract":"<p><p>Defective mineralization of bone matrix results in osteomalacia, which universally affects the skeletal system and dentition and manifests alongside the clinically and radiologically more obvious growth plate disorder rickets in young children. Given that radiological signs of osteomalacia are limited, most hypomineralization disorders are diagnosed based on their clinical features and/or typical biochemical signatures, especially after the closure of growth plates. Evaluation of histomorphometry (HM) parameters and bone mineral density distribution (BMDD) via quantitative backscattered electron imaging (qBEI) from transiliac bone biopsy samples enables the exploration of the true skeletal disease burden of osteomalacia and the assessment of the impact of treatment. The diagnosis of various acquired and heritable disorders of osteomalacia based on clinical, biochemical, radiological and biomaterial HM features is discussed here. The most common acquired cause of osteomalacia remains dietary calcium and solar/dietary vitamin D deficiencies. Rare heritable causes result from mutations in genes involved in calcitriol synthesis and action (resulting in calcipaenia), fibroblast growth factor 23 production or degradation or tubulopathies (resulting in phosphopaenia) or reduced hydrolysis of the mineralization blocker inorganic pyrophosphate (resulting from hypophosphatasia). On bone biopsy, osteomalacia manifests as increased osteoid indices on static HM, with mineralization lag on tetracycline-labelled dynamic HM. Calcipaenic disorders typically display additional HM features of secondary hyperparathyroidism which include increased osteocyte surface from increased bone turnover, peritrabecular marrow fibrosis and cortical thinning. BMDD in osteomalacic conditions shows an increased amount of lowly mineralized bone tissue and increased heterogeneity in mineralization when compared to normal individuals. Medical assessment should focus on identification of biochemical disease signatures which differ between these osteomalacic entities but are essential for early diagnosis and treatment monitoring, with the aim of achieving full matrix mineralization and prevention of this hidden disease.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"91"},"PeriodicalIF":3.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526528","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":"Microbes Matter: Exploring the Connection Between Infant Gut Microbiota and Bone Development.","authors":"Perry Caviness, Bharath K Mulakala, Oxana P Lorenzo, Tianming Yao, Stephen R Lindemann, Fernanda Rosa, Laxmi Yeruva, Jin-Ran Chen","doi":"10.1007/s00223-025-01395-5","DOIUrl":"10.1007/s00223-025-01395-5","url":null,"abstract":"<p><p>Human milk, compared to milk formula, is considered the optimal source of nutrition for infants as it can shape offspring microbiome composition, which is necessary for the production of key biomolecules that aid in development of infant physiological systems. A variety of factors in human milk can influence infant microbiome composition. One such factor is the type of oligosaccharides present, which is determined in part by maternal secretor status and itself determined by expression of fucosyltransferase-2 (FUT2). The aim of this study was to investigate the effects of secretor or non-secretor human milk as well as infant milk formula on infant gut microbiome composition and whether these changes in microbiota impact bone development. Fecal microbiota transfer from infants fed human milk from secretor mothers (SMM) or non-secretor mothers (NSM) as well as those fed infant milk formula (MFM) into 21-day-old germ-free mice were performed. After 35 days, gut microbiome composition and bone development were analyzed using 16S rRNA sequencing and µCT analysis. At the genus level, Phocaeicola and Akkermansia are upregulated for SMM and NSM mice respectively, while family Ruminococcaceae is increased for MFM mice. Percent bone volume (BV/TV) and trabecular number (Tb N) were significantly decreased for MFM mice but unaltered for SMM and NSM mice compared to germ-free controls (GF CTRL). Measurement of bone marrow plasma inflammatory factor levels shows a significant increase in TNF-α and IL-1β for SMM and NSM mice, both potential promoters of osteoclastogenesis under certain conditions, compared to MFM and GF CTRL mice. Data suggests that milk formula feeding may suppress infant bone growth and development by altering gut microbiome composition.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"90"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511605","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":"Identification and Validation of Novel Lipids Linked to Bone Mineral Density Change and Fracture Risk.","authors":"Canchen Ma, Ziyuan Shen, Jing Tian, Yvette L Schooneveldt, Corey Giles, Flavia Cicuttini, Graeme Jones, Peter J Meikle, Feng Pan","doi":"10.1007/s00223-025-01399-1","DOIUrl":"10.1007/s00223-025-01399-1","url":null,"abstract":"<p><p>To identify and validate lipid metabolites associated with bone mineral density (BMD) change and fracture risk through integrated Mendelian randomization (MR) and observational analyses. Two-sample MR analysis was first performed to uncover potential causal relationships between 32 lipid classes and 576 lipid species and BMD and fractures. Identified signatures were subsequently validated in an independent cohort (N = 492), where lipids, BMD, and fracture status were measured at two time points, 8 years apart. The false discovery rate method was employed to control multiple testing. Linear and log binomial mixed-effects models were used to analyze lipid associations with hip BMD and fracture risk, respectively. Two-sample MR revealed seven lipid classes causally associated with BMD and/or fractures, including acylcarnitine (AC), cholesteryl ester (CE), sphingomyelin (SM), phosphatidylinositol (PI), GM3 ganglioside (GM3), alkylphosphatidylcholine (PC(O)) and triacylglycerol (TG). Causal associations were found between 18 lipid species across these classes and BMD, and 10 lipid species were associated with fractures. Validation in an independent longitudinal cohort confirmed associations for total SM, SM(d18:1/16:0), SM(d18:2/24:0), and CE(18:3) with hip BMD change (β ranging from - 0.036 to - 0.012 g/cm², per log µM increase, p < 1.13 × 10^-2). Total SM, total GM3, and SM(d18:2/18:1), SM(d18:2/22:0), SM(d18:2/17:0) were associated with an increased risk of fractures (RR ranging from 1.038 to 1.290 g/cm², per log µM increase, p < 5 × 10^-2) over 8 years. Our findings suggest that alterations in lipid metabolism play a causal role in bone remodeling and fracture risk. This warrants further investigation into the mechanisms of lipid-mediated BMD changes and the potential for identifying patients at 'high risk' of osteoporotic fracture.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"89"},"PeriodicalIF":3.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483257","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":"Bone Mineral Density and Trabecular Bone Score in Children, Adolescents and Young Adults with Familial Dysautonomia.","authors":"Bat El Bar-Aluma, Ronit Porges, Liana Tripto-Shkolnik, Shlomit Keler, Noah Gruber, Adi Dagan, Dalit Modan-Moses, Yael Levy-Shraga","doi":"10.1007/s00223-025-01400-x","DOIUrl":"10.1007/s00223-025-01400-x","url":null,"abstract":"<p><p>Familial dysautonomia (FD) is characterized by skeletal morbidity, including osteoporosis and increased fracture risk. We aimed to assess bone mineral density (BMD) and trabecular bone score (TBS) in individuals with FD, and to explore correlations with disease severity. This retrospective study included all the patients with FD who performed at least one dual-energy X-ray absorptiometry (DXA) scan at our institution during 2015-2023. Demographic and clinical data obtained from medical records included: medical treatment, anthropometric measurements, Functional Severity Scale (FuSS) score, balance assessment, the Brief Ataxia Rating Scale score, ambulation ability, blood test results and fracture history. Forty-one patients (21 males) had at least one DXA scan. The median age at the first scan was 25 years (range 7-47). The mean BMD Z-score was - 1.2 ± 1.5 at the lumbar spine and - 1.3 ± 1.1 at the bilateral proximal femur. The mean TBS Z-score was - 1.8 ± 1.6. The bilateral proximal femur BMD Z-score correlated with better scores of balance (r = 0.612, p = 0.001), ambulation (r = 0.627, p = 0.001) and ataxia (r = - 0.470, p = 0.015). For 67% of the patients, C-terminal telopeptides of type I collagen (CTX) was above the normal range for age. Both CTX and procollagen type I N-terminal propeptide (P1NP) correlated negatively with FuSS (r = - 0.515, p = 0.10 and r = - 0.619, p = 0.042, respectively) and with L_1-4 Z-scores (r = - 0.681, p = 0.03 and r = - 0.700, p = 0.02, respectively). Individuals with FD had low BMD and TBS Z-scores. These parameters were correlated to disease severity, specifically to balance and ambulation. The bone resorption marker was high and negatively correlated with disease severity.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"88"},"PeriodicalIF":3.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483234","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":"A Mosaic PHEX Variant in Hypophosphatemic Rickets: Distinguishing Postzygotic Mutation from Sex Chromosome Aneuploidy.","authors":"Wu Tzen Lim, Marni Nenke, Lesley Rawlings, Amanda Wells, Cassandra Vakulin, Wendy Waters, Sunita De Sousa","doi":"10.1007/s00223-025-01388-4","DOIUrl":"10.1007/s00223-025-01388-4","url":null,"abstract":"<p><p>Hereditary hypophosphatemic rickets, most commonly caused by X-linked dominant PHEX variants, leads to hypophosphatemia and bone mineralization defects. We identified a novel mosaic nonsense variant in the PHEX gene on the X chromosome by next-generation sequencing-c.1971C > A, p.(Tyr657X)--in a man with clinical features of hypophosphatemic rickets. As the variant was only found in 67% of DNA reads, we considered the possibility of sex chromosome aneuploidy (e.g. a 48,XXXY sex chromosome complement with an unaffected X chromosome i.e. variant on 2 of 3 X chromosomes producing a variant allele frequency of approx. 67%) or a postzygotic mutation resulting in the PHEX variant in some but not all cells. His mother was clinically unaffected, and he did not have features of Klinefelter's syndrome, favouring postzygotic mutation over sex chromosome aneuploidy. We excluded sex chromosome aneuploidy through karyotype studies showing a 46,XY status. As the event must therefore be a postzygotic variant to produce the reduced variant allele frequency, his parents are not at risk of having the variant. However, X chromosome postzygotic mutations in men may be inherited by female offspring (depending on the mosaic status of gonadal tissue). The patient's karyotype result was thus integral in the investigation of disease mechanism and in guiding family genetic counselling.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"87"},"PeriodicalIF":3.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324494","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":"A Systematic Review of the Effects of Bisphosphonates on Osteoblasts In Vitro.","authors":"Henrique Hadad, Laís Kawamata de Jesus, Maísa Pereira da Silva, Maria Eduarda de Freitas Santana Oliveira, Fernando Pozzi Semeghini Guastaldi, Ola Nilsson, Roberta Okamoto, Francisley Ávila Souza","doi":"10.1007/s00223-025-01390-w","DOIUrl":"10.1007/s00223-025-01390-w","url":null,"abstract":"<p><p>Bisphosphonates (BPs) are widely used to treat bone disorders, prevent skeletal-related events, and manage bone metastasis. These drugs are synthetic analogs of pyrophosphate and primarily function by inhibiting osteoclast activity. However, increasing evidence suggests that they also have an effect on osteoblasts. This systematic review aims to evaluate how bisphosphonates affect osteoblasts by summarizing findings from in vitro studies on the impact of BPs on osteoblast lineage cells, addressing the following question: \"Do bisphosphonates affect osteoblast cell lineage function?\". For this purpose, the PICO framework was followed, and 36 articles were selected for inclusion in this review. The data suggest that the molecular mechanisms in osteoblasts can vary depending on the specific type of bisphosphonate, as well as the concentration and duration of treatment, leading to either stimulation or inhibition of osteogenesis. Additionally, studies have shown that certain BPs, such as zoledronic acid, can interfere with osteoblast differentiation, proliferation, gene expression, and mineralization capacity, potentially impairing bone healing. On the other hand, other drugs, such as alendronate, demonstrate more positive effects on cell function. Some drugs, such as pamidronate and clodronate, exhibited mixed effects; however, it was observed that high concentrations of these drugs can lead to cytotoxic effects. Despite these adverse effects, it is important to recognize that the clinical benefits of managing bone disorders often outweigh the potential risks highlighted in this review.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"86"},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309581","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":"Association of the Appendicular Skeletal Muscle Mass-to-Visceral Fat Area Ratio with Cause-Specific Mortality in Diabetes.","authors":"Shuwu Wei, Jiale Zhang, Huijuan Zheng, Weimin Jiang, Jie Yang, Yaoxian Wang, Weihong Chen, Weiwei Sun","doi":"10.1007/s00223-025-01389-3","DOIUrl":"10.1007/s00223-025-01389-3","url":null,"abstract":"<p><p>The relationship between muscle mass and visceral fat with mortality risk in diabetes has been extensively studied. This study investigates the association between the appendicular skeletal muscle mass-to-visceral fat area ratio (SVR) and cardiovascular and cancer-related mortality in diabetic patients in the United States. A nationwide cohort study was conducted using NHANES data (2011-2018), including 1439 diabetic patients with dual-energy X-ray absorptiometry (DXA) measurements. Weighted Cox proportional hazards models and restricted cubic splines (RCS) were employed to evaluate the association between SVR and cause-specific mortality rates. Weighted receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of SVR and other conventional indicators in predicting mortality. After adjusting for multiple confounding factors, SVR showed a linear negative association with cardiovascular and cancer-related mortality in diabetes. Each 0.01-unit increase in SVR was associated with a 3% reduction in the risk of cardiovascular death and a 2% reduction in cancer-related death. However, SVR demonstrated weak diagnostic performance for both cardiovascular and cancer mortality, with weighted AUCs of 0.520 and 0.527, respectively, compared to other metrics including BMI, WC, ASM, and VFA. Although SVR was significantly associated with cardiovascular and cancer mortality, its predictive performance was not superior to that of simpler or more established indicators, suggesting that it has limited clinical utility for predicting mortality in diabetic patients.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"85"},"PeriodicalIF":3.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293368","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":"Characterization of Bone Matrix Mineralization and Osteocyte Lacunar Density Unveils Microstructural Impairment at the Main Femoral Fracture-Initiating Site in Type 2 Diabetes Mellitus.","authors":"Aleksandar Cirovic, Jelena Jadzic, Christine Plumeyer, Danica Djukic, Vladimir Zivkovic, Slobodan Nikolic, Danijela Djonic, Marija Djuric, Björn Busse, Petar Milovanovic","doi":"10.1007/s00223-025-01396-4","DOIUrl":"https://doi.org/10.1007/s00223-025-01396-4","url":null,"abstract":"<p><p>This study aimed to perform microstructural characterization of the increased fragility of human bone in type 2 diabetes mellitus (T2DM) by exploring the matrix mineralization and osteocyte lacunar density at the superolateral femoral neck-the typical fracture-initiating site. Postmortem specimens of the full-length superolateral femoral neck from 16 elderly men with T2DM and age-matched non-DM controls were examined using backscattered-electron microscopy in terms of mineralization parameters and parameters of osteocyte lacunar density. The T2DM and control groups did not differ in age and body mass index (p > 0.05). In the endocortical region, T2DM was associated with a lower degree of mineralization (lower CaMean: p = 0.04), a higher proportion of extremely low-mineralized areas (higher CaLow: p = 0.027), and greater mineralization heterogeneity (higher CaWidth: p = 0.003) relative to controls. However, there were no significant intergroup differences in mineralization parameters in the periosteal region. In the endocortical region, T2DM showed lower unmineralized (p = 0.006) and total osteocyte lacunar number (Lc.N) per bone area (B.Ar) (p = 0.018) coupled with a higher percentage of mineralized lacunae (%Mn.Lc) relative to controls (p = 0.05). In the periosteal region, only Lc.N/B.Ar was lower in T2DM (p = 0.004). As for the trabecular compartment, T2DM was associated with lower trabecular CaMean (p = 0.048) and higher trabecular CaLow and CaWidth (p = 0.005, p = 0.007). Altered pattern of mineralization in the cortical (especially in the endocortical region) and trabecular compartments of the superolateral femoral neck and reduced cortical osteocyte lacunar density are structural hallmarks of bone fragility in T2DM.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"84"},"PeriodicalIF":3.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282454","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}