Kristen J Koltun, Matthew B Bird, Jennifer N Forse, Mita Lovalekar, Qi Mi, Brian J Martin, Bradley C Nindl
{"title":"Tibial Skeletal Adaptations in Male and Female Marine Corps Officer Candidates Undergoing 10 Weeks of Military Training.","authors":"Kristen J Koltun, Matthew B Bird, Jennifer N Forse, Mita Lovalekar, Qi Mi, Brian J Martin, Bradley C Nindl","doi":"10.1007/s00223-024-01339-5","DOIUrl":"https://doi.org/10.1007/s00223-024-01339-5","url":null,"abstract":"<p><p>Military training improves tibial density, structure, and estimated strength; however, men and women may adapt differently. Most work performed in military populations has assessed changes in bone health during initial entry programs, a timeframe at the beginning of a service member's career when bones may be more adaptable to a novel mechanical stimulus. The purpose of this investigation was to examine changes in tibial volumetric bone mineral density (vBMD), structure, and estimated strength, and biomarkers of bone metabolism (P1NP, osteocalcin, TRAP5b, sclerostin) between male and female candidates measured at the start and end of United States Marine Corps Officer Candidates School (OCS), a 10-week military training program attended by older service members (~ 25 y/o) who may have previous military experience. Peripheral quantitative computed tomography (pQCT) of the tibia (n = 375) and blood draws (n = 385) were performed. Generalized linear mixed effects modeling compared changes between sexes over time. Increases in total and trabecular vBMD were observed at the 4% site in the total sample, but total and cortical vBMD decreased in female candidates at the 66% site. Periosteal circumference at the 38% and 66% sites increased in the total sample. Estimated strength increased similarly in male and female candidates at the 4% and 38% sites but only increased in male candidates at the 66% site. Concentrations of P1NP and osteocalcin increased similarly in both sexes, although sclerostin and TRAP5b decreased only in male candidates. Measures of tibial vBMD, width, and estimated strength increased following OCS consistent with adaptive bone formation.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"27"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944958","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":"Administration of Bisphosphonate Preparations to Mice with Mild-type Hypophosphatasia Reduces the Quality of Spontaneous Locomotor Activity.","authors":"Aki Nakamura-Takahashi, Satoshi Ishizuka, Kengo Hirai, Satoru Matsunaga, Norio Kasahara, Seikou Shintani, Shinichi Abe, Masataka Kasahara","doi":"10.1007/s00223-024-01326-w","DOIUrl":"10.1007/s00223-024-01326-w","url":null,"abstract":"<p><p>Hypophosphatasia (HPP) is a congenital bone disease caused by tissue-nonspecific mutations in the alkaline phosphatase gene. It is classified into six types: severe perinatal, benign prenatal, infantile, pediatric, adult, and odonto. HPP with femoral hypoplasia on fetal ultrasonography, seizures, or early loss of primary teeth can be easily diagnosed. In contrast, pediatric, adult, and odonto types of HPP over 4 years of age are less likely to be diagnosed because they do not have typical symptoms. Consequently, it may be misdiagnosed as common osteoporosis, and treatments incompatible with HPP may be implemented. The purpose of this study was to analyze the effects of bisphosphonate preparations administration on the femur of Akp2<sup>+/-</sup> mice, a mild-type HPP mice model. Zoledronic acid (Zol) was subcutaneously administered to 4-week-old Akp2<sup>+/-</sup> mice at 1 mg/kg (volume: 200 μL) once a week for a total of 5 times. Afterward, spontaneous locomotor activity analysis was performed, and serum and femur bones were collected at 9 weeks of age. Additionally, micro-computed tomography (CT) analysis, histological analysis, and analysis of the expression levels of various marker proteins and genes were performed. Age-matched Akp2<sup>+/+</sup> mice served as controls. The results demonstrated that the administration of Zol to Akp2<sup>+/-</sup> mice, compared to Akp2<sup>+/+</sup> mice, insufficiently promotive bone formation, torn femoral head cartilage, and decreased spontaneous locomotor activity. Therefore, it is important to accurately diagnose patients with mild-type HPP.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"30"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945377","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}
Laura Freitas, Andrea Bezerra, Ana Resende-Coelho, Leonardo Maciel, Maria Gomez-Lazaro, Tânia Amorim, Ricardo Fernandes, Hélder Fonseca
{"title":"Effect of Eight Months of Swimming on Bone Quality of Different Anatomical Regions: A Study on Wistar Rat Models.","authors":"Laura Freitas, Andrea Bezerra, Ana Resende-Coelho, Leonardo Maciel, Maria Gomez-Lazaro, Tânia Amorim, Ricardo Fernandes, Hélder Fonseca","doi":"10.1007/s00223-024-01333-x","DOIUrl":"10.1007/s00223-024-01333-x","url":null,"abstract":"<p><p>Swimming is a popular sport with several health benefits, but its effects on bone quality are controversial possibly due to distinct effects on different anatomical regions. Our aim was to investigate the effect of 8-month swimming on bone growth, mass, geometry, trabecular microarchitecture and osteocyte density of the lumbar vertebrae, femur and tibia of male rats. Wistar rat models were assigned to either a swimming (n = 10; 2h/d, 5 d/week) or a physically active control group (n = 10) for 8 months, after which they were sacrificed and their lumbar vertebrae, femur and tibia assessed for bone mass, cortical geometry, trabecular microarchitecture and osteocyte density through µ-CT and histology. Variables were compared between groups through independent samples t tests. Swimming animals displayed higher vertebral trabecular connectivity and lower trabecular separation compared to controls. However, femur length, trabecular and cortical bone mass and cortical thickness were lower compared to controls. At the tibia, animals from the swimming group also presented lower trabecular number and connectivity and higher trabecular separation. Osteocyte density at the femur and vertebra was similar between groups. Eight months of swimming negatively affected bone mass, cortical geometry and trabecular microarchitecture at the femur and tibia whilst having a favourable effect on vertebral trabecular microarchitecture. These results suggest that swimming has divergent effects on different anatomical regions.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"29"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944941","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}
Elena Della Morte, Maria Pina Notarangelo, Stefania Niada, Chiara Giannasi, Federica Fortuna, Francesca Cadelano, Elisabetta Lambertini, Roberta Piva, Anna Teresa Brini, Letizia Penolazzi
{"title":"Adipose-Derived Stromal Cell Conditioned Medium on Bone Remodeling: Insights from a 3D Osteoblast-Osteoclast Co-Culture Model.","authors":"Elena Della Morte, Maria Pina Notarangelo, Stefania Niada, Chiara Giannasi, Federica Fortuna, Francesca Cadelano, Elisabetta Lambertini, Roberta Piva, Anna Teresa Brini, Letizia Penolazzi","doi":"10.1007/s00223-024-01335-9","DOIUrl":"https://doi.org/10.1007/s00223-024-01335-9","url":null,"abstract":"<p><p>This study describes the potential of the conditioned medium (CM) from adipose-derived mesenchymal stromal cells (ASCs) to affect the response of bone cells and support bone remodeling. This was in particular assessed by an in vitro model represented by a 3D human osteoblast-osteoclast co-culture. It has been reported that the effects of ASCs are predominantly attributable to the paracrine effects of their secreted factors, that are present as soluble factors or loaded into extracellular vesicles. They may affect various biological processes, including bone turnover. Our interest was to provide further evidence to support ASC-CM as a promising cell-free therapeutic agent for the treatment of bone loss. ASC-CM was characterized using nanoparticle tracking analysis (NTA), cytofluorimetry, and proteomic analysis. Human osteoblasts (hOBs) from vertebral lamina were cultured with monocytes, as osteoclasts (hOCs) precursors, in a Rotary cell culture system for 14 days. Histochemical analysis was performed to evaluate the effect of ASC-CM on bone-specific markers such as tartrate-resistant acid phosphatase (TRAP), osteopontin (OPN), RUNX2, Collagen 1 (COL1), and mineral matrix. ASC-CM characterization confirmed the content of CD63/CD81/CD9 positive extracellular vesicles. Proteomic dataset considering bone-remodeling-related keywords identified 16 processes significantly enriched. The exposure of hOBs/hOCs aggregates to ASC-CM induced increase of OPN, COL I, and RUNX2, and significantly induced mineral matrix deposition, while significantly reducing TRAP expression. These data demonstrated that CM from ASCs contains a complex of secreted factors able to control either bone resorption or bone formation and requires further investigations to deeply analyze their potential therapeutic effects.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"26"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945376","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}
Sandra Baumann, Lilian Sewing, Cyril Traechslin, Wilma Verhagen-Kamerbeek, Leticia Grize, Marius Kraenzlin, Christian Meier
{"title":"Serum Pentosidine in Relation to Obesity in Patients with Type 2 Diabetes and Healthy Controls.","authors":"Sandra Baumann, Lilian Sewing, Cyril Traechslin, Wilma Verhagen-Kamerbeek, Leticia Grize, Marius Kraenzlin, Christian Meier","doi":"10.1007/s00223-024-01338-6","DOIUrl":"10.1007/s00223-024-01338-6","url":null,"abstract":"<p><p>Pentosidine (PEN), a surrogate marker of advanced glycation end-product formation, reflects increased non-enzymatic cross-linking in bone collagen, which is thought to be an important determinant of bone fragility in type 2 diabetes mellitus (T2DM). We aimed to investigate serum concentrations of PEN in patients with T2DM and controls without T2DM and to examine its relationship with bone parameters and metabolic state such as glycaemic control, insulin resistance and body weight. In a cross-sectional study-design, data from postmenopausal women and men with T2DM (n = 110) and controls without T2DM (n = 111) were evaluated. Serum PEN was measured using an ELISA-based assay (CSB-E09415h, Cusabio). In addition, biochemical markers of glucose metabolism and bone turnover markers were measured. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry. After adjustment for age, gender and body mass index (BMI), serum PEN was significantly higher in patients with T2DM compared to controls (p = 0.02) and most prominently in women with T2DM (p = 0.09). We found a strong association of serum PEN concentrations with BMI in the entire study population (R = 0.43, p < 0.001) as well as in patients with T2DM (R = 0.28, p < 0.01). While bone turnover markers were significantly decreased, and BMD increased in patients with T2DM, only weak or no associations were observed between these skeletal surrogate markers and serum PEN. We conclude that serum PEN is strongly associated with BMI with highest levels in obese women with T2DM. Adjustment for patient's weight is needed when evaluating serum PEN levels in patients with T2DM.Clinical Trial Information: NCT02551315.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"25"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944942","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":"Effects of Pregnancy and Lactation on Bone Microstructure and Material Properties in a Rat Model of Bariatric Surgery.","authors":"Malory Couchot, Françoise Schmitt, Morgane Mermet, Céline Fassot, Guillaume Mabilleau","doi":"10.1007/s00223-024-01321-1","DOIUrl":"https://doi.org/10.1007/s00223-024-01321-1","url":null,"abstract":"<p><p>Obesity is a major public health issue worldwide. Despite various approaches to weight loss, the most effective technique for reducing obesity, as well as diabetes and associated diseases, is bariatric surgery. Increasingly, young women without children are undergoing bariatric surgery, vertical sleeve gastrectomy (VSG) being the most common procedure nowadays. However, despite several reports suggesting bone loss after VSG, little is known about the potential additive effects of gestation and lactation after VSG to bone health. This study investigated the combined effects of pre-gestational VSG and subsequent gestation/lactation on bone metabolism in a rat model fed a high fat high sugar (HFHS) diet, with a focus on bone biomechanics, mass, microarchitecture and material properties. Furthermore, bone mass and remodelling were followed longitudinally by microCT prior to surgery, 4 weeks post-surgery, after weaning and at sacrifice. Significant alterations in bone mass and microarchitecture, characterized by changes in trabecular thickness and number, as well as changes in bone formation and resorption were influenced by both surgery and reproductive demands. Mechanical testing at sacrifice demonstrated compromised long bone fragility, in rat with HFHS regardless of the surgical procedure (Sham or VSG). Furthermore, analysis of bone material properties highlighted potential disruptions in the pattern of bone mineralization in sham and VSG animals fed a HFHS diet. These findings underscore the complex interplay between pre-gestational VSG and subsequent gestation/lactation in modulating bone metabolism in the investigated rat model. The preclinical rat model may help with optimizing surgical strategies and developing targeted interventions to mitigate potential bone-related complications associated with VSG in reproductive-aged individuals.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"23"},"PeriodicalIF":3.3,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926778","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":"Treatment Advances in Tumor-Induced Osteomalacia.","authors":"Iris R Hartley, Kelly L Roszko","doi":"10.1007/s00223-024-01317-x","DOIUrl":"https://doi.org/10.1007/s00223-024-01317-x","url":null,"abstract":"<p><p>Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by hypersecretion of fibroblast growth factor 23 (FGF23) by typically benign phosphaturic mesenchymal tumors (PMTs). FGF23 excess causes chronic hypophosphatemia through renal phosphate losses and decreased production of 1,25-dihydroxy-vitamin-D. TIO presents with symptoms of chronic hypophosphatemia including fatigue, bone pain, weakness, and fractures. Definitive treatment is surgical resection of the PMT with wide margins. Other therapeutic options are necessary when the tumor is unable to be localized, not amenable to complete resection, or when the patient is not a good surgical candidate. Alternative ablative approaches such as radiotherapy, radiofrequency ablation, and cryoablation, have been used with variable success and limited follow up. Medical management is warranted both prior to definitive therapy and in non-operable cases to improve symptoms and allow for bone remineralization. Oral phosphate and calcitriol were the mainstay of medical therapy, however, the development of burosumab, a monoclonal blocking antibody to FGF23, has introduced an approved therapy that improves hypophosphatemia and symptoms in patients with TIO. In select cases, cinacalcet can be an effective adjuvant to phosphate and calcitriol. Continued monitoring for tumor growth is necessary while on medical therapy. Infigratinib, a selective FGFR tyrosine-kinase inhibitor targeting a causative tumoral fusion protein, can reverse the biochemical findings of TIO and possibly reduce tumor mass; however, its use is constrained by serious side effects. Overall, innovations in medical and interventional treatments have broadened therapeutic options for patients with PMTs, particularly in cases where a curative surgical resection is not possible.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"24"},"PeriodicalIF":3.3,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926783","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}
Juliette Jousse, Blandine Merle, Elodie Feurer, Emmanuelle Vignot, Roland Chapurlat
{"title":"A Qualitative Approach to Quality of Life in Fibrous Bone Dysplasia /McCune Albright Syndrome: Looking Beyond Quantitative Analysis.","authors":"Juliette Jousse, Blandine Merle, Elodie Feurer, Emmanuelle Vignot, Roland Chapurlat","doi":"10.1007/s00223-024-01332-y","DOIUrl":"10.1007/s00223-024-01332-y","url":null,"abstract":"<p><p>This study explores FD/MAS patient's perceptions about their disease and its impact on their quality of life. We have evaluated quality of life (QoL) in French Fibrous Dysplasia/MacCune-Albright Syndrome (FD/MAS) patients using a qualitative approach with focus groups to explore perceptions, symptoms and limitations associated with FD/MAS and a quantitative method with the Short Form-36 (SF36) to quantify QoL. Focus groups revealed the heterogeneity of FD forms and allowed for understanding the reasons of reduced QoL. Patients identified pain as the dominant symptom. The impact on mental health was explained by diagnostic uncertainty, disease chronicity and rarity and the inconsistent effectiveness of therapies. Patients talked about disability but also of coping strategies. They expressed their need for comprehensive and multi-disciplinary care from medical and paramedical professionals familiar with their pathology. The quantitative questionnaire SF36 confirmed reduced QoL in these patients compared with the French general population in all sub-domains: physical function (72.1 versus 84.4, p = 0.0001), physical role (60.5 versus 81.1, p = 0.0004), body pain (58.7 versus 72.4, p = 0.0004), general health (50.08 versus 67.6, p < 0.0001), energy (44.58 versus 57.2, p < 0.0001), social function (61.34 versus 80.5, p < 0.0001), emotional role (57.98 versus 81.3, p = 0.0002) and emotional well-being (57.98 versus 81.3, p = 0.0097). Polyostotic patients had poorer QoL compared with monostotic patients. A better understanding of the disease experience and expectations of FD patients will enable practitioners to provide care better adapted to patients' needs, and pave the way for optimizing DF care.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"18"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920772","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}
Gregorio Bevilacqua, Stefania D'Angelo, Faidra Laskou, Elena Zaballa, Nicholas C Harvey, Elaine M Dennison
{"title":"The Association between Social Support and Musculoskeletal Health in Community-Dwelling Older Adults: Findings from the Hertfordshire Cohort Study.","authors":"Gregorio Bevilacqua, Stefania D'Angelo, Faidra Laskou, Elena Zaballa, Nicholas C Harvey, Elaine M Dennison","doi":"10.1007/s00223-024-01307-z","DOIUrl":"10.1007/s00223-024-01307-z","url":null,"abstract":"<p><p>Previous studies suggest social support is associated with musculoskeletal health in later life. We explored this relationship further in community-dwelling older adults, by considering associations between different aspects of social support and musculoskeletal health in community-dwelling adults. Participants from the Hertfordshire Cohort Study reported level of confiding/emotional, practical, and negative support using the Close Persons Questionnaire. Muscle strength was measured by grip strength dynamometry, and physical capability by timed up-and-go, chair rises, and walking speed tests. Bone mineral density (BMD) was assessed using dual-energy x-ray absorptiometry. Linear regression, adjusted for age, sex, body mass index (BMI), alcohol, smoking, physical activity, social class, and diet, was used for analysis. 1842 men and women (mean age 65.7 years) participated. Low emotional support correlated with weaker grip strength and poorer physical capability tests, although estimates were not robust to adjustment for confounders. Low practical support was linked to shorter timed up-and-go (β - 0.171, 95%CI - 0.319, - 0.024) and walking speed times (β - 0.157, 95%CI - 0.306, - 0.007), following adjustment for confounders. Negative support (i.e. the perceived inadequacy of the support received) was associated with lower grip strength (β - 0.145, 95%CI - 0.223, - 0.067) and slower walking speeds (β 0.159, 95%CI 0.004, 0.314). No social support exposures were associated with BMD. Different types of social support are linked to various measures of musculoskeletal health in older adults. Limited requirement for practical support correlated with better physical capability, while negative support correlated with poorer outcomes. No social support measure was associated with BMD.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"8"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920768","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 a Novel Col1a1<sup>G643S/+</sup> Osteogenesis Imperfecta Mouse Model with Insights into Skeletal Phenotype, Fragility, and Therapeutic Evaluations.","authors":"Hiroyuki Saitou, Yasuhisa Ohata, Shinji Takeyari, Chiaki Nishizawa, Hirofumi Nakayama, Makoto Fujiwara, Yasuji Kitabatake, Takuo Kubota, Keiichi Ozono","doi":"10.1007/s00223-024-01320-2","DOIUrl":"10.1007/s00223-024-01320-2","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is an inheritable skeletal disorder characterized by bone fragility often caused by pathogenic variants in the COL1A1 gene. Current OI mouse models with a glycine substitution in Col1a1 exhibit excessive severity, thereby limiting long-term pathophysiological analysis and drug effect assessments. To address this limitation, we constructed a novel OI mouse model mimicking a patient with OI type III. This was achieved by introducing a G-to-A transversion at nucleotide position 2428 in the Col1a1 gene via CRISPR-Cas9 technology in C57BL/6 J mice. The resulting heterozygous variant mice (Col1a1<sup>G643S/+</sup>) displayed reduced body weight and pronounced skeletal abnormalities. Micro-CT analysis at 12 weeks revealed decreased vertebral bone parameters and altered cortical bone characteristics, indicative of bone fragility. Additionally, the abnormalities of the anisotropy, complexity, connectivity, and structure of trabecular bone were revealed. A three-point bending test confirmed the fragility, with reduced displacement and fracture energy in both sexes. Furthermore, we evaluated the effect of 4-phenylbutyric acid on the bone in Col1a1<sup>G643S/+</sup> mice at 12 weeks, observing no significant effects, likely due to the absence of collagen retention in the ER in this model. Despite being a moderate OI model, Col1a1<sup>G643S/+</sup> mice manifest a distinct and fragile bone phenotype, making them suitable for extended studies. This model offers a valuable platform for investigating long-term pathophysiological aspects of OI and assessing the efficacy of potential therapeutic interventions.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"13"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920748","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}