Calcified Tissue International最新文献

{"title":"Evaluation of Potential Roles of Zinc Finger Homeobox 3 (Zfhx3) Expressed in Chondrocytes and Osteoblasts on Skeletal Growth in Mice.","authors":"Gustavo A Gomez, Anakha Udayakumar, Sheila Pourteymoor, Garrett Dennis, Weirong Xing, Subburaman Mohan","doi":"10.1007/s00223-024-01265-6","DOIUrl":"10.1007/s00223-024-01265-6","url":null,"abstract":"<p><p>Bone formation is tightly modulated by genetically encoded molecular proteins that interact to regulate cellular differentiation and secretion of bony matrix. Many transcription factors are known to coordinate these events by controlling gene transcription within networks. However, not all factors involved are known. Here, we identified a novel function for Zinc Finger Homeobox 3 (Zfhx3), a gene encoding a transcription factor, as a regulator of bone metabolism. We knocked out Zfhx3 conditionally in mice in either chondrocytes or osteoblasts and characterized their bones by micro-CT in 12-week-old mice. We observed a negative effect in linear bone growth in both knockout mice but reduced bone mass only in mice with Zfhx3 deleted in osteoblasts. Loss of Zfhx3 expression in osteoblasts affected trabecular bone mass in femurs and vertebrae in both sexes but influenced cortical bone volume fraction only in females. Moreover, transcriptional analysis of femoral bones in osteoblast Zfhx3 conditional knockout mice revealed a reduced expression of osteoblast genes, and histological evaluation of trabecular bones suggests that Zfhx3 causes changes in bone formation and not resorption. The loss of Zfhx3 causes reductions in trabecular bone area and osteoid volume, but no changes in the expression of osteoclast differentiation markers or number of TRAP stained osteoclasts. These studies introduce Zfhx3 as a relevant factor toward understanding gene regulatory networks that control bone formation and development of peak bone mass.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859086","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":"Exogenous Angiotensin-(1-7) Provides Protection Against Inflammatory Bone Resorption and Osteoclastogenesis by Inhibition of TNF-α Expression in Macrophages.","authors":"Jiayi Ren, Hideki Kitaura, Takahiro Noguchi, Fumitoshi Ohori, Aseel Marahleh, Jinghan Ma, Kayoko Kanou, Ziqiu Fan, Itaru Mizoguchi","doi":"10.1007/s00223-024-01257-6","DOIUrl":"10.1007/s00223-024-01257-6","url":null,"abstract":"<p><p>Renin-angiotensin-aldosterone system plays a crucial role in the regulation of blood pressure and fluid homeostasis. It is reported to be involved in mediating osteoclastogenesis and bone loss in diseases of inflammatory bone resorption such as osteoporosis. Angiotensin-(1-7), a product of Angiotensin I and II (Ang I, II), is cleaved by Angiotensin-converting enzyme 2 and then binds to Mas receptor to counteract inflammatory effects produced by Ang II. However, the mechanism by which Ang-(1-7) reduces bone resorption remains unclear. Therefore, we aim to elucidate the effects of Ang-(1-7) on lipopolysaccharide (LPS)-induced osteoclastogenesis. In vivo, mice were supracalvarial injected with Ang-(1-7) or LPS ± Ang-(1-7) subcutaneously. Bone resorption and osteoclast formation were compared using micro-computed tomography, tartrate-resistant acid phosphatase (TRAP) stain, and real-time PCR. We found that Ang-(1-7) attenuated tumor necrosis factor (TNF)-α, TRAP, and Cathepsin K expression from calvaria and decreased osteoclast number along with bone resorption at the suture mesenchyme. In vitro, RANKL/TNF-α ± Ang-(1-7) was added to cultures of bone marrow-derived macrophages (BMMs) and osteoclast formation was measured via TRAP staining. The effect of Ang-(1-7) on LPS-induced osteoblasts RANKL expression and peritoneal macrophages TNF-α expression was also investigated. The effect of Ang-(1-7) on the MAPK and NF-κB pathway was studied by Western blotting. As a result, Ang-(1-7) reduced LPS-stimulated macrophages TNF-α expression and inhibited the MAPK and NF-κB pathway activation. However, Ang-(1-7) did not affect osteoclastogenesis induced by RANKL/TNF-α nor reduce osteoblasts RANKL expression in vitro. In conclusion, Ang-(1-7) alleviated LPS-induced osteoclastogenesis and bone resorption in vivo via inhibiting TNF-α expression in macrophages.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726950","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 Characteristics of Gut Microbiota and Its Relation with Diet in Postmenopausal Osteoporosis.","authors":"Tinglong Chen, Fan Meng, Ning Wang, Yongqiang Hao, Lingjie Fu","doi":"10.1007/s00223-024-01260-x","DOIUrl":"10.1007/s00223-024-01260-x","url":null,"abstract":"<p><p>The gut microbiome is linked to osteoporosis. Previous clinical studies showed inconsistent results. This study aimed to characterize the gut microbiota feature and reveal its relation with diet in postmenopausal osteoporosis. Fifty-five postmenopausal women with osteoporosis (Op group) and forty-four age-matched postmenopausal women (normal bone mineral density, Con group) were included in this study. Fecal microbiota was collected and analyzed by shallow shotgun sequencing. Food frequency questionnaires were collected from both groups, and Spearman analysis was used to clarify its correlation with gut microbiota. A total of 2671 species from 29 phyla, 292 families, 152 orders, 80 classes were detected in the study. The two groups had no significant difference in the α and β diversity (p > 0.05). At the genus level, Anaerostipes was enriched in Op group (p < 0.05). At species level, Methanobrevibacter smithii, Bifidobacterium animalis, Rhodococcus defluvii, Lactobacillus plantarum, and Carnobacterium mobile were enriched in the Op group, while Bacillus luciferensis, Acetivibrio cellulolyticus, Citrobacter amalonaticus, and Bifidobacterium breve were differentially enriched in the Con group. Food frequency questionnaire showed that postmenopausal women with osteoporosis intaked more red meat, beer, white and red wine (p < 0.05), and the Con group had more yogurt, fruit, and tea consumption. Red meat consumption had a significant negative correlation with Streptosporangiales (p < 0.01) and Actinomadura (p < 0.05). Fruits intake negatively correlated with Nocardiaceae, Rhodococcus, and Rhodococcus defluvii (p < 0.05). More yogurt intake was consistently correlated with a greater abundance of Streptosporangiales. This study suggests that gut microbiota is significantly altered in the postmenopausal osteoporosis population at genus and species levels, and specific dietary intake might relate to these changes.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765540","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":"Global 'Conditional' Assurance of Romosozumab Safety: International Consensus on the Uniqueness of Adverse Cardiovascular Events in Japan.","authors":"Hiroshi Kawaguchi","doi":"10.1007/s00223-024-01267-4","DOIUrl":"10.1007/s00223-024-01267-4","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854943","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":"Muscle Performance as a Predictor of Bone Health: Among Community-Dwelling Postmenopausal Japanese Women from Setagaya-Aoba Study.","authors":"Takahisa Ohta, Hiroyuki Sasai, Naoki Kikuchi, Koichi Nakazato, Takanobu Okamoto","doi":"10.1007/s00223-024-01269-2","DOIUrl":"10.1007/s00223-024-01269-2","url":null,"abstract":"<p><p>Osteoporosis is a significant health concern for postmenopausal women, necessitating efficient screening methods for bone health. This study explores the potential of muscle function, assessed through the 30-s chair stand test (CS-30), as an indicator for low bone stiffness in this demographic, aiming to establish a practical threshold for large-scale fitness surveillance without the need for specialized tools. We analyzed data from 1055 community-dwelling postmenopausal Japanese women, aged 41-89 years, collected between 2016 and 2019. Participants underwent CS-30 to evaluate muscle function alongside quantitative ultrasound (QUS) measurements to assess bone stiffness. The cohort was divided into two groups for the development and validation of a cutoff point for low bone stiffness, defined as a QUS speed of sound less than 1487.3 m/s. The CS-30 cutoff was determined using receiver operating characteristic (ROC) curve analysis and validated through logistic regression, accounting for age, body mass index, and smoking status. Among 577 postmenopausal women, 16.0% exhibited low bone stiffness. In the development group (n = 382), ROC analysis identified a CS-30 cutoff of 25 repetitions for detecting low bone stiffness, with an area under the curve of 0.744 (P < 0.001). In the validation group (n = 195), participants performing ≥ 25 repetitions had a higher risk of low bone stiffness compared to those performing ≤ 24 repetitions. The CS-30 test is an effective preliminary screening tool for identifying postmenopausal women at risk of low bone stiffness, with a threshold of 25 repetitions. This method could facilitate early detection of individuals at higher osteoporosis risk, promoting timely intervention.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892926","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":"Developing Cut-off Values for Low and Very Low Bone Mineral Density at the Thoracic Spine Using Quantitative Computed Tomography.","authors":"Andia Cheneymann, Josephine Therkildsen, Laust Dupont Rasmussen, Jesper Thygesen, Christin Isaksen, Ellen-Margrethe Hauge, Simon Winther, Morten Böttcher","doi":"10.1007/s00223-024-01268-3","DOIUrl":"10.1007/s00223-024-01268-3","url":null,"abstract":"<p><p>Osteoporosis is under-diagnosed while detectable by measuring bone mineral density (BMD) using quantitative computer tomography (QCT). Opportunistic screening for low BMD has previously been suggested using lumbar QCT. However, thoracic QCT also possesses this potential to develop upper and lower cut-off values for low thoracic BMD, corresponding to the current cut-offs for lumbar BMD. In participants referred with chest pain, lumbar and thoracic BMD were measured using non-contrast lumbar- and cardiac CT scans. Lumbar BMD cut-off values for very low (< 80 mg/cm³), low (80-120 mg/cm³), and normal BMD (> 120 mg/cm³) were used to assess the corresponding thoracic values. A linear regression enabled identification of new diagnostic thoracic BMD cut-off values. The 177 participants (mean age 61 [range 31-74] years, 51% women) had a lumbar BMD of 121.6 mg/cm³ (95% CI 115.9-127.3) and a thoracic BMD of 137.0 mg/cm³ (95% CI: 131.5-142.5), p < 0.001. Categorization of lumbar BMD revealed 14%, 35%, and 45% in each BMD category. When applied for the thoracic BMD measurements, 25% of participants were reclassified into a lower group. Linear regression predicted a relationship of Thoracic BMD = 0.85 * Lumbar BMD + 33.5, yielding adjusted thoracic cut-off values of < 102 and > 136 mg/cm³. Significant differences in BMD between lumbar and thoracic regions were found, but a linear relationship enabled the development of thoracic upper and lower cut-off values for low BMD in the thoracic spine. As Thoracic CT scans are frequent, these findings will strengthen the utilization of CT images for opportunistic detection of osteoporosis.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995371","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 Relationship between Sclerostin and Kidney Transplantation Mineral Bone Disorders: A Molecule of Controversies.","authors":"Baris Afsar, Rengin Elsurer Afsar, Yasar Caliskan, Krista L Lentine","doi":"10.1007/s00223-024-01261-w","DOIUrl":"10.1007/s00223-024-01261-w","url":null,"abstract":"<p><p>Kidney transplantation is the most effective treatment option for most patients with end-stage kidney disease due to reduced mortality, decreased cardiovascular events and increased quality of life compared to patients treated with dialysis. However, kidney transplantation is not devoid of both acute and chronic complications including mineral bone disorders (MBD) which are already present in patients with chronic kidney disease (CKD) before kidney transplantation. The natural history of MBD after kidney transplantation is variable and new markers are needed to define MBD after kidney transplantation. One of these promising molecules is sclerostin. The main action of sclerostin is to inhibit bone formation and mineralization by blocking osteoblast differentiation and function. In kidney transplant recipients (KTRs), various studies have shown that sclerostin is associated with graft function, bone parameters, vascular calcification, and arterial stiffness although non-uniformly. Furthermore, data for inhibition of sclerostin with monoclonal antibody romosozumab for treatment of osteoporosis is available for general population but not in KTRs which osteoporosis is highly prevalent. In this narrative review, we have summarized the studies investigating the change of sclerostin before and after kidney transplantation, the relationship between sclerostin and laboratory parameters, bone metabolism and vascular calcification in the context of kidney transplantation. We also pointed out the uncertainties, explained the causes of divergent findings and suggest further potential study topics regarding sclerostin in kidney transplantation.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792028","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":"3D U-Net Neural Network Architecture-Assisted LDCT to Acquire Vertebral Morphology Parameters: A Vertebral Morphology Comprehensive Analysis in a Chinese Population.","authors":"Duoshan Ma, Yan Wang, Xinxin Zhang, Danyang Su, Mengze Ma, Baoxin Qian, Xiaopeng Yang, Jianbo Gao, Yan Wu","doi":"10.1007/s00223-024-01255-8","DOIUrl":"10.1007/s00223-024-01255-8","url":null,"abstract":"<p><p>To evaluate the feasibility of acquiring vertebral height from chest low-dose computed tomography (LDCT) images using an artificial intelligence (AI) system based on 3D U-Net vertebral segmentation technology and the correlation and features of vertebral morphology with sex and age of the Chinese population. Patients who underwent chest LDCT between September 2020 and April 2023 were enrolled. The Altman and Pearson's correlation analyses were used to compare the correlation and consistency between the AI software and manual measurement of vertebral height. The anterior height (Ha), middle height (Hm), posterior height (Hp), and vertebral height ratios (VHRs) (Ha/Hp and Hm/Hp) were measured from T1 to L2 using an AI system. The VHR is the ratio of Ha to Hp or the ratio of Hm to Hp of the vertebrae, which can reflect the shape of the anterior wedge and biconcave vertebrae. Changes in these parameters, particularly the VHR, were analysed at different vertebral levels in different age and sex groups. The results of the AI methods were highly consistent and correlated with manual measurements. The Pearson's correlation coefficients were 0.855, 0.919, and 0.846, respectively. The trend of VHRs showed troughs at T7 and T11 and a peak at T9; however, Hm/Hp showed slight fluctuations. Regarding the VHR, significant sex differences were found at L1 and L2 in all age bands. This innovative study focuses on vertebral morphology for opportunistic analysis in the mainland Chinese population and the distribution tendency of vertebral morphology with ageing using a chest LDCT aided by an AI system based on 3D U-Net vertebral segmentation technology. The AI system demonstrates the potential to automatically perform opportunistic vertebral morphology analyses using LDCT scans obtained during lung cancer screening. We advocate the use of age-, sex-, and vertebral level-specific criteria for the morphometric evaluation of vertebral osteoporotic fractures for a more accurate diagnosis of vertebral fractures and spinal pathologies.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626077","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":"Association Between Dietary Acid Load and Grip Strength in Adults 50 Years and Older: A Cross-Sectional Study.","authors":"Elsa M Konieczynski, Lisa Ceglia, Elise Reitshamer, Bess Dawson-Hughes","doi":"10.1007/s00223-024-01258-5","DOIUrl":"10.1007/s00223-024-01258-5","url":null,"abstract":"<p><p>Minimal data exist on whether the acid-base balance of the diet is linked to muscle strength. The aim of this study was to determine if dietary acid load is associated with grip strength in a nationally representative sample of middle- to older-age adults. We examined the cross-sectional association of grip strength with dietary acid load quantified through potential renal acid load (PRAL) and net endogenous acid production (NEAP) in 4,059 adults aged 50 years and older in the 2011-2014 NHANES survey cycles. PRAL and NEAP were estimated from two 24-h recalls and categorized into sex-specific quartiles. Grip strength was measured on a dynamometer. Multiple linear regression models were used to determine the associations of PRAL and NEAP (as quartiles) with grip strength for men and women separately, adjusting for total energy, age, race/ethnicity, weight, physical activity, smoking, serum 25-hydroxyvitamin D, and estimated glomerular filtration rate. Mean grip strength was 26.8 ± 0.2 kg in women and 43.0 ± 0.4 kg in men. Adjusted grip strength was inversely associated with quartiles of PRAL (p_trend = 0.049) and NEAP (p_trend = 0.034) in women with quartile 4 vs 1 differences of - 1.21 and - 1.08 kg (both p < 0.05), respectively. Adjusted grip strength was not associated with PRAL or NEAP in men. Overall, we found inverse associations between dietary acid load and grip strength in middle- and older-age women, suggesting that an alkaline diet may be important in maintaining muscle strength in this population. There was no association between dietary acid load and grip strength in men.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751187","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":"Early-Onset Osteoporosis: Molecular Analysis in Large Cohort and Focus on the PLS3 Gene.","authors":"Maxence Mancini, Roland Chapurlat, Bertrand Isidor, Marine Desjonqueres, Guillaume Couture, Pascal Guggenbuhl, Régis Coutant, Salima El Chehadeh, Mélanie Fradin, Aline Frazier, Alice Goldenberg, Pascaline Guillot, Eugénie Koumakis, Nadia Mehsen-Cêtre, Massimiliano Rossi, Élise Schaefer, Sabine Sigaudy, Valérie Porquet-Bordes, Élisabeth Fontanges, Pauline Letard, Thomas Edouard, Rose-Marie Javier, Martine Cohen-Solal, Thomas Funck-Brentano, Corinne Collet","doi":"10.1007/s00223-024-01288-z","DOIUrl":"https://doi.org/10.1007/s00223-024-01288-z","url":null,"abstract":"<p><p>Osteoporosis is a skeletal disorder characterized by abnormal bone microarchitecture and low bone mineral density (BMD), responsible for an increased risk of fractures and skeletal fragility. It is a common pathology of the aging population. However, when osteoporosis occurs in children or young adults, it strongly suggests an underlying genetic etiology. Over the past two decades, several genes have been identified as responsible for this particular kind of considered monogenic early-onset osteoporosis (EOOP) or juvenile osteoporosis, the main ones being COL1A1, COL1A2, LRP5, LRP6, WNT1, and more recently PLS3. In this study, the objective was to characterize a large cohort of patients diagnosed with primary osteoporosis and to establish its diagnosis yield. The study included 577 patients diagnosed with primary osteoporosis and its diagnosis yield was established. To this end, next-generation sequencing (NGS) of a panel of 21 genes known to play a role in bone fragility was carried out. A genetic etiology was explained in about 18% of cases, while the others remain unexplained. The most frequently identified gene associated with EOOP is LRP5, which was responsible for 8.2% of the positive results (47 patients). As unexpected, 17 patients (2.9%) had a variant in PLS3 which encodes plastin 3. Alterations of PLS3 are associated with dominant X-linked osteoporosis, an extremely rare disease. Given the rarity of this disease, we focused on it. It was observed that males were more affected than females, but it is noteworthy that three females with a particularly severe phenotype were identified. Of these three, two had a variant in an additional gene involved in EOP, illustrating the probable existence of digenism. We significantly increase the number of variants potentially associated with EOOP, especially in PLS3. The results of our study demonstrate that molecular analysis in EOOP is beneficial and useful.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307154","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}