Calcified Tissue International最新文献

{"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}

{"title":"Lower Limb Bone Mineral Density Reduction is Closely Relative With Diabetic Peripheral Neuropathy in the Postmenopausal Women and Men Over 50 Years Old With T2DM: A cross-Sectional, Controlled Study.","authors":"Xiaopu Lin, Xiaoming Wen, Yanting Zhou, Junxi Wu, Zhiyang Lu, Lingling Xu","doi":"10.1007/s00223-025-01397-3","DOIUrl":"https://doi.org/10.1007/s00223-025-01397-3","url":null,"abstract":"<p><p>A cross-sectional, controlled study was designed to investigate the relationship between BMD at different sites and DPN in patients with type 2 diabetes mellitus (T2DM). Nerve conduction parameters and BMD of different sites were measured. Pearson's correlation analysis and receiver operating characteristic (ROC) analysis were performed to examine the relationship between BMD at different sites and DPN. The proportion of osteoporosis (OP) in the DPN group was higher compared to the non-DPN group (p < 0.05). The Z/T scores of femoral neck and hip joint BMD were lower in the DPN group (all p < 0.05). Sensory nerve amplitude, sensory nerve conduction velocity, and motor nerve amplitude were significantly lower in the osteoporosis group and positively correlated with the T scores of femoral neck and hip joint BMD in postmenopausal women and men over 50 years old with T2DM. ROC analysis revealed the following cutoff points for T2DM duration combined with femoral neck/hip joint BMD T scores to predict DPN in postmenopausal women and men over 50 years old with T2DM: (duration: 8 years, femoral neck T score: - 1.6; AUC = 0.64; 95% CI 0.60-0.68; sensitivity: 64.2%; specificity: 52.9%, p < 0.001) and (duration: 8 years, hip joint T score: - 1.6; AUC = 0.64; 95% CI 0.61-0.68; sensitivity: 60.8%; specificity: 56.0%, p < 0.001). A significant association was observed between reduced lower limb BMD and DPN in the postmenopausal women and men over 50 years old with T2DM.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"83"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282455","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":"Exploring the Role of FGF7 in Tumor-Induced Osteomalacia. Clinic-Pathologic Analysis in a Patient with a Sino-Nasal Phosphaturic Mesenchymal Tumor.","authors":"L Colangelo, F R Di Ciommo, B Palmisano, R Scrivo, M Della Monaca, J Pepe, C Cipriani, C Alessandri, V Valentini, M Riminucci, S Minisola, F Conti, A Corsi","doi":"10.1007/s00223-025-01394-6","DOIUrl":"https://doi.org/10.1007/s00223-025-01394-6","url":null,"abstract":"<p><p>Tumor-induced osteomalacia (TIO) is an ultrarare paraneoplastic syndrome due to the overproduction of Fibroblast Growth Factor 23 (FGF23). Although other phosphate-regulating substances (i.e., \"phosphatonins\") have been demonstrated to be expressed in tumors associated with TIO, very limited information is available about their circulating levels and clinical significance. Here, we report a patient with a long-standing history of low serum phosphate values due to a sino-nasal phosphaturic mesenchymal tumor (PMT), in which the co-expression of FGF23 and FGF7 was detected in the neoplastic tissue and their serum levels determined before and after surgical tumor excision. The serum level of FGF23 was increased (312.0 pg/mL) before surgery and promptly normalized 24 h after tumor excision. In contrast, the value of FGF7 was high (202.6 pg/mL) before surgery, fell at 24 h after surgery (108.6 pg/mL), increased again after one week (252.0 pg/mL), and finally normalized (33.4 pg/mL) one year later, when also serum phosphate was in the normal range. This is the first sino-nasal PMT in which expression of FGF7 was observed and the first case of TIO in which the serum levels of FGF7 were monitored during the course of the disease (i.e., before and after tumor excision). Even though \"phosphatonins\" in addition to FGF23 are thought to contribute to the phosphate wasting leading to TIO, the observed increase in FGF7 levels one week after surgery (+ 31.66% compared to the preoperative value), when phosphate levels tended to normalize, may suggest a mild, if ever, phosphaturic effect of FGF7. Further studies are needed to define the mechanisms underlying the different post-surgical time-dependent decrease in the serum levels of FGF23 and FGF7 and the role of FGF7 in patients with TIO and more in general in phosphate homeostasis.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"82"},"PeriodicalIF":3.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246580","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":"Mineral Content and Extracellular Matrix Protein Expression in Mouse Growth Plates During Epiphyseal Fusion: An Observational Study.","authors":"Xinhang Yu, Megumi Nakamura, Miyuki Mayanagi, Itaru Mizoguchi, Yasuyuki Sasano","doi":"10.1007/s00223-025-01391-9","DOIUrl":"10.1007/s00223-025-01391-9","url":null,"abstract":"<p><p>In humans, the growth plate cartilage is completely replaced by bone in late puberty, resulting in epiphyseal fusion. However, in rats and mice, commonly used experimental model systems, the growth plate does not fuse completely even after sexual maturation, making it difficult to elucidate mechanisms involved in epiphyseal fusion. In this study, we investigated age-related changes in the mouse growth plate to better understand the process of epiphyseal fusion. We used scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM/EDS) to examine the distributions and concentrations of minerals in the growth plate. In SEM images, the hypertrophic zone was observed as a bright area and other zones as dark areas at 10 weeks of age (W10). The bright area was further expanded at W55 than at W10. EDS analysis showed that P and Ca concentrations were high in this area, while C and O concentrations were low, indicating that the growth plate had calcified during aging. Alcian blue histochemistry revealed that the glycosaminoglycans of aggrecan were distributed in the growth plate at both W10 and W55. Immunohistochemistry showed that aggrecan and type II collagen were expressed throughout the growth plate at W10, but sparsely at W55. Type I collagen was expressed weak at both W10 and W55. Type X collagen and MMP-13 expression were observed in the hypertrophic zone at W10 but not at W55. This study demonstrated that although the mouse growth plate calcifies with age, it remains calcified cartilage for an extended period without being replaced by bone.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"81"},"PeriodicalIF":3.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233268","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":"Patterns of Bone Mineral Density Loss at Multiple Skeletal Sites Following Recent Menopause in Users and Non-Users of Menopausal Hormone Therapy.","authors":"Kara L Holloway-Kew, Amelia G Morse, Kara B Anderson, Mark A Kotowicz, Julie A Pasco","doi":"10.1007/s00223-025-01392-8","DOIUrl":"10.1007/s00223-025-01392-8","url":null,"abstract":"<p><p>Post-menopausal bone loss has been well described, however fewer studies have focussed on changes around the time of menopause. This study describes bone mineral density (BMD) loss following recent menopause, stratified by hormone replacement therapy (HT) use. Women (n = 287) who self-reported recent menopause (≥ 12 months to < 5 yr since last menstrual period) for at least one assessment phase of the Geelong Osteoporosis Study were included. BMD was measured using Lunar DPX-L and GE-Prodigy machines. Time since menopause was calculated for each participant at each assessment phase and divided into three categories: < 5 yr, 5-10 yr and ≥ 10 yr. BMD loss was expressed as: (i) cumulative loss over time, (ii) absolute value per year and (iii) percentage loss per year. Proportions of women with normal BMD, osteopenia and osteoporosis were also calculated. Cumulative BMD loss was lower among HT users than non-users at all sites and time categories, except the femoral neck. Compared to the other time categories, HT non-users had a greater rate of BMD loss (expressed as an absolute value or percentage per year) during the first five years postmenopause at the ultra-distal forearm and lumbar spine. No differences were observed between the time categories for HT users. The proportions of women with osteopenia and osteoporosis increased across each of the time categories, but patterns differed by skeletal site, being more pronounced for the femoral neck and mid-forearm sites. Rates of bone loss were greater at the lumbar spine and ultra-distal forearm during the first five years following menopause.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"80"},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224402","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":"Comparison of Type 2 Diabetes Risk in Osteoporosis Patients Treated with Denosumab or Alendronate: A Nationwide Cohort Study.","authors":"Kyoung Jin Kim, Seol A Jang, Su Jin Kwon, Gi Hyeon Seo, Kyoung Min Kim","doi":"10.1007/s00223-025-01385-7","DOIUrl":"https://doi.org/10.1007/s00223-025-01385-7","url":null,"abstract":"<p><p>Recent studies have suggested potential metabolic effects of anti-osteoporotic medications, but their impact on type 2 diabetes mellitus (T2D) risk remains unclear. This study investigated the incidence of T2D in patients with osteoporosis treated with denosumab or alendronate. Using the Korean Health Insurance Review and Assessment Service database, we identified 316,026 patients who received either denosumab or alendronate between October 2017 and June 2022. After 1:3 propensity score matching, 1136 denosumab users and 3303 alendronate users were included. The primary outcome was incident T2D, defined as a new diagnosis followed by an antidiabetic medication prescription within six months. Over a median follow-up of 4.7 years, 57 (5.0%) denosumab users and 196 (5.9%) alendronate users developed T2D, with incidence rates of 10.7 and 12.4 per 1000 person-years, respectively. Denosumab use was not significantly associated with reduced T2D risk (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.64-1.15). Additional adjustment for chronic kidney disease and fractures during follow-up yielded an HR of 0.84 (95% CI 0.62-1.13; P = 0.25). Fine-Gray competing risk analysis considering death produced similar results (HR 0.84, 95% CI 0.62-1.13; P = 0.24). Subgroup analyses showed consistent findings across sex, age groups, comorbidities, and concurrent medication use. These findings suggest no significant difference in T2D risk between denosumab and alendronate users in osteoporosis patients. Both medications appear to have comparable metabolic effects. Further large-scale studies with longer follow-up are warranted to clarify the long-term impact of osteoporosis treatments on diabetes risk.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"78"},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186648","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":"Stress During Lactation: A Hidden Link to Offspring Bone Health.","authors":"Ranjitha Chandrashekar, Bharath K Mulakala, Manoj Gurung, Geetanjali Venna, Jolene R Rearick, Brenda Onyekweli, Meghan L Ruebel, Jasmine Dada-Fox, Jasmina A Zeledon, Rachelanne Talatala, Kayleigh Rodriguez, Laura R Osborn, Mary Grace Bishop, Brenda Smith, Kimberly E Stephens, Edralin A Lucas, Laxmi Yeruva","doi":"10.1007/s00223-025-01378-6","DOIUrl":"10.1007/s00223-025-01378-6","url":null,"abstract":"<p><p>Early-life resource limitation is one factor that could have a major impact on child health and development. Thus, using a rat model of limited bedding and nesting (LBN), we investigated the postnatal bone development, mineralization, and microarchitecture. Pregnant Sprague-Dawley rats were subjected to a LBN model to induce chronic early-life stress (CES), while a control group was maintained under standard conditions. The offspring were assessed at postnatal day (PND) 10, 21, and 35. Tibial length was measured, and tibial and lumbar vertebral bone mineral density (BMD), content (BMC), and area (BMA) were assessed using dual-energy X-ray absorptiometry (DXA). Bone microarchitecture was examined using microcomputed tomography (μCT). Changes in gene expression from the lumbar vertebrae were analyzed by transcriptome. At PND 10, there were no significant differences in BMD and BMC between the treatment groups, but tibial length was significantly decreased by CES. By PND 21, tibial BMC and BMA were significantly reduced in the CES group, indicating impaired bone mineral accumulation. At PND 35, tibial length remained significantly reduced by CES, while BMD and BMC differences were less affected. Vertebral BMA and BMC were reduced by CES. μCT analysis of tibial cortical bone showed significant changes in cortical thickness and bone volume at PND 10 and 21, respectively. For the lumbar vertebrae, μCT data indicated significant increases in the degree of anisotropy and structural model index at PND 21 and 35, respectively. Transcriptome analyses revealed significant differential expression of genes involved in immune response, cellular repair, and stress adaptation at PND 21 but not at PND 10 and PND 35. CES significantly disrupts BMC, BMD, length, and microarchitecture differently at various stages of postnatal development. Transcriptome analyses suggest that these changes are mediated by alterations in gene expression related to immune function and cellular repair. Future research should focus on tracking the longitudinal impacts of CES on bone health from infancy into adulthood, and exploring nutritional interventions, stress reduction programs, and molecular studies that can mitigate the negative effects of CES on bone.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"79"},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186649","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}