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Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway

Chinese Medical Journal 2023年第12期136卷 1468-1477页

作者： Hongqi Zhang Gang Xiang Jiong Li Sihan He Yunjia Wang Ang Deng Yuxiang Wang Chaofeng Guo Department of Spine Surgery and Orthopaedics Xiangya HospitalCentral South UniversityChangshaHunan 410000China National Clinical Research Center for Geriatric Disorder Xiangya HospitalCentral South UniversityChangshaHunan 410000China

Background:Congenital scoliosis(CS)is a complex spinal malformation of unknown etiology with abnormal bone *** growth factor 23(FGF23),secreted by osteoblasts and osteocytes,can inhibit bone formation and *** research aims to investigate the relationship between CS and ***:We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target ***23 mRNA levels in the peripheral blood of CS patients and age-matched controls were *** operator characteristic(ROC)curve analyses were conducted to evaluate the specificity and sensitivity of *** expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3(FGFr3)/tissue non-specific alkaline phosphatase(TNAP)/osteopontin(OPN)in primary osteoblasts from CS patients(CS-Ob)and controls(CT-Ob)were *** addition,the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were ***:DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins,accompanied by increased mRNA *** patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography(CT)values compared with *** FGF23 mRNA levels were negatively correlated with the CT value of the spine,and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for ***,significantly increased levels of FGF23,FGFr3,OPN,impaired osteogenic mineralization and lower TNAP levels were observed in ***,FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels,while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in *** of CS-Ob was rescued after FGF23 ***:Our results suggested increased peripheral blood FGF23 levels,decreased bone mineral density in CS patients,and a good predictive ability of CS by peripheral blood FGF23 leve

关键词： Scoliosis Fibroblast growth factor 23 Fibroblast growth factor receptor 3 osteopenia

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Impaired autophagy activity-induced abnormal differentiation of bone marrow stem cells is related to adolescent idiopathic scoliosis osteopenia

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Chinese Medical Journal 2023年第17期136卷 2077-2085页

作者： Hongqi Zhang Guanteng Yang Jiong Li Lige Xiao Chaofeng Guo Yuxiang Wang Department of Spine Surgery and Orthopaedics Xiangya HospitalCentral-South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorder Xiangya HospitalCentral-South UniversityChangshaHunan 410008China

Background:osteopenia has been well documented in adolescent idiopathic scoliosis(AIS).Bone marrow stem cells(BMSCs)are a crucial regulator of bone *** previous study revealed a decreased osteogenic ability of BMSCs in AIS-related osteopenia,but the underlying mechanism of this phenomenon remains ***:A total of 22 AIS patients and 18 age-matched controls were recruited for this *** and bone mass were measured in all *** marrow blood was collected for BMSC isolation and *** and adipogenic induction were performed to observe the differences in the differentiation of BMSCs between the AIS-related osteopenia group and the control ***,a total RNA was extracted from isolated BMSCs to perform RNA sequencing and subsequent ***:A lower osteogenic capacity and increased adipogenic capacity of BMSCs in AIS-related osteopenia were *** in mRNA expression levels between the AIS-related osteopenia group and the control group were identified,including differences in the expression of LRRC17,DCLK1,PCDH7,TSPAN5,NHSL2,and *** Encyclopedia of Genes and Genomes enrichment analyses revealed several biological processes involved in the regulation of autophagy and *** Western blotting results of autophagy markers in BMSCs suggested impaired autophagic activity in BMSCs in the AIS-related osteopenia ***:Our study revealed that BMSCs from AIS-related osteopenia patients have lower autophagic activity,which may be related to the lower osteogenic capacity and higher adipogenic capacity of BMSCs and consequently lead to the lower bone mass in AIS patients.

关键词： Adolescent idiopathic scoliosis Bone marrow stem cell Autophagy osteopenia

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The Influence of Health Qigong on the Subjectively Expressed Psychophysical State of Patients with Rheumatoid Arthritis,Rheum,Osteoporosis,osteopenia

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Chinese Medicine and Culture 2018年第3期1卷 150-154页

作者： Ilinka Acimovic Chinese Association of Health Qigong

This study assesses the impact of exercise on the health of the Qigong(Jibengong,Health Qigong Ba Duan Jin and Health Qigong Yi Jin Jing)in patients with rheumatoid arthritis,rheumatism,osteoporosis,*** the given questionnaire we have come up with data showing how and how much health qigong affects the patients with rheumatoid arthritis,rheumatism,osteoporosis,osteopenia according to the subjective assessment.

关键词： Ba Duan Jin depression health qigong Jibengong osteopathy osteopenia osteoporosis physical activity rheumatoid arthritis therapy Yi Jin Jing

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Osteonecrosis of the jaw in a patient taking once-yearly infusion of zoledronic acid for osteopenia

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Case Reports in Clinical Medicine 2013年第9期2卷 535-537页

作者： Takako Imai Tanaka Charles Donald Taylor Department of Biomedical and Diagnostic Sciences University of Detroit Mercy School of Dentistry Detroit USA Department of Patient Management University of Detroit Mercy School of Dentistry Detroit USA

Osteonecrosis of the jaw (ONJ) is an adverse effect of nitrogen-containing bisphosphonates. Advancing age, intravenous administration of zoledronic acid (ZOL), history of dento-alveolar surgery, and concomitant systemic diseases such as diabetes are known as risk factors for developing ONJ. However, despite numerous studies, the exact pathophysiology remains unclear and management strategies are largely anecdotal. Once-yearly intravenously administered 5 mg ZOL was approved by the US Food and Drug Administration in 2007 for the treatment of osteoporosis and its efficacy with 3 year-regimen had been recently proven in preventing new clinical fracture. Although occurrences of ONJ have been reported to be rare with this drug administration, available data is very limited and long-term outcomes are lacking. We present a case of ONJ identified in an osteopenic patient with an intermittent but long standing sore mouth related to exposed mandibular bone. Once-yearly infusion of zoledronic acid used in the treatment of osteopenia may contribute to the spontaneous development of ONJ, especially in those presenting with multiple comorbidity factors. This report suggests the importance of health care professionals keeping abreast of new developments in this area and providing appropriate information to their patients.

关键词： osteopenia Osteoporosis Bisphosphonates Osteonecrosis Letrozole Once-Yearly Zoledronic Acid ONJ ARONJ BRONJ

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Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling

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Genes & Diseases 2024年第2期11卷 964-977页

作者： Chengzhi Wu Hengyu Liu Dongmei Zhong Xiaoming Yang Zhiheng Liao Yuyu Chen Shun Zhang Deying Su Baolin Zhang Chuan Li Liru Tian Caixia Xu Peiqiang Su Guangdong Provincial Key Laboratory of Orthopedics and Traumatology Department of Spine SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Research Center for Translational Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Precision Medicine Institute The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Department of Orthopedics Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Guangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research School of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China

Mutation of the MAPK7 gene was related to human ***7 regulated the development of limb bones and skulls in ***,the role of MAPK7 in vertebral development is still *** this study,we constructed Col2a1-cre;Mapk7 f/f transgenic mouse model to delete Mapk7 in cartilage,which displayed kyphosis and ***,Mapk7 loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes,which impaired chondrocyte hypertrophy and attenuated vertebral *** vivo,systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by Mapk7 *** study firstly clarified the mechanism by which MAPK7 was involved in vertebral development,which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.

关键词： Chondrocyte hypertrophy Growth plate Kyphosis MAPK7 MEF2C osteopenia PI3K/AKT PTEN

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Hepatocellular carcinoma and musculoskeletal system: A narrative literature review

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World Journal of Gastroenterology 2024年第15期30卷 2109-2117页

作者： Jelena Jadzic Danijela Djonic Center of Bone Biology Faculty of MedicineUniversity of BelgradeBelgrade 11000Serbia

Musculoskeletal alterations in hepatocellular carcinoma(HCC)are less common than liver-related ***,they can significantly impact the quality of life and overall prognosis of patients with *** main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asym-ptomatic and unapparent during routine clinical *** narrative literature review aimed to provide a comprehensive overview of the contem-porary literature related to the changes in the musculoskeletal system in patients with HCC,focusing on its clinical implications and underlying etiopathogenetic *** bone metastases are the most common skeletal alterations associated with HCC,which could be associated with an increased risk of low-trauma bone ***,previous studies reported that osteopenia,sarcopenia,and myosteatosis are associated with poor clinical outcomes in patients with *** though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients,these complications are frequently overlooked in the clinical management of patients with *** together,contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient *** research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.

关键词： Hepatocellular carcinoma osteopenia Osteoporosis Sarcopenia Bone metastases Bone fragility

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Burden of bone disease in chronic pancreatitis:A systematic review and meta-analysis

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World Journal of Gastroenterology 2023年第8期29卷 1374-1394页

作者： Ankit Chhoda Maria Jose Hernandez-Woodbine Nana Afua Akkya Addo Syed Alishan Nasir Alyssa Grimshaw Craig Gunderson Awais Ahmed Steven D.Freedman Sunil G.Sheth Department of Gastroenterology Beth Israel Deaconess Medical CenterBostonMA 02215United States Department of Medicine Norwalk HospitalYale School of MedicineNorwalkCT 06850United States Cushing/Whitney Medical Library Yale UniversityNew HavenCT 06510United States General Internal Medicine Yale School of MedicineNew HavenCT 06510United States

BACKGROUND Bone disease is an under-recognized cause of morbidity in chronic pancreatitis(CP).Over the past decade,publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the *** To quantify the prevalence of osteopenia,osteoporosis,and fragility fractures in CP patients and investigate the associated clinical features and *** A systematic search identified studies investigating bone disease in CP patients from Cochrane Library,Embase,Google Scholar,Ovid Medline,PubMed,Scopus,and Web of Science,from inception until October *** outcomes included prevalence of osteopenia,osteoporosis,and fragility fractures,which were metaanalyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical *** Twenty-one studies were included for systematic review and 18 studies were included for *** pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2%(95%CI:35.2%-47.3%)and 20.9%(95%CI:14.9%-27.6%),*** pooled prevalence of fragility fractures described among CP was 5.9%(95%CI:3.9%-8.4%).Metaregression revealed significant association of pancreatic enzyme replacement therapy(PERT)use with prevalence of osteoporosis[coefficient:1.7(95%CI:0.6-2.8);Posteopenia,osteoporosis or fragility *** of data on systemic inflammation,CP severity,and bone mineralization parameters precluded a formal *** This meta-analysis confirms significant bone disease in patients with *** than PERT use,we observed no patient or study-specific factor to be significantly associated with CP-related bone *** studies are needed to identify confounders,at-risk population,and to understand the mechanisms of CP-related bone disease an

关键词： Chronic pancreatitis Fractures Osteoporosis osteopenia Bone disease

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Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn’s disease

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World Journal of Gastroenterology 2006年第35期12卷 5680-5686页

作者： Sarah A Bartram Robert T Peaston David J Rawlings David Walshaw Roger M Francis Nick P Thompson Musculoskeletal unit Freeman HospitalNewcastle-upon-Tyne United Kingdom Department of Biochemistry Freeman Hospital Newcastle-upon-Tyne United Kingdom Regional Medical Physics Department Newcastle General Hospital United Kingdom Dept of Statistics University of Newcastle upon Tyne United Kingdom Musculoskeletal unit Freeman Hospital Newcastle-upon-Tyne United Kingdom Department of Medicine Freeman Hospital Newcastle-upon-Tyne United Kingdom

AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn’s disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX). RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for thebone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.

关键词： Crohn's disease Osteoporosis osteopenia Bone mineral density

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Effect of rapamycin on hepatic osteodystrophy in rats with portasystemic shunting

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World Journal of Gastroenterology 2006年第28期12卷 4504-4510页

作者： Schalk W van der Merwe Maria M Conradie Robert Bond Brenda J Olivier Elongo Fritz Martin Nieuwoudt Rhena Delport Tomas Slavik Gert Engelbrecht Del Kahn Enid G Shephard Maritha J Kotze Nico P de Villiers Stephen Hough Department of Internal Medicine and Gastroenterology ImmunologyHepatology and GI- research laboratoryUniversity of PretoriaSouth Africa Department of Internal Medicine and Endocrinology University of StellenboschSouth Africa Department of Internal Medicine and Gastroenterology1 Hepatology and GI- research laboratoryUniversity of PretoriaSouth Africa Department of Hepatology and GI- research laboratory University of PretoriaSouth Africa Department of Chemical Pathology University of PretoriaSouth Africa Department of Ampath pathology PretoriaSouth Africa Department of Surgery Grootte Schuur HospitalUniversity of Cape TownSouth Africa MRC Liver Research Centre Grootte Schuur HospitalUniversity of Cape TownSouth Africa Department of Genecare Molecular Genetics Christiaan Barnard Memorial HospitalCape TownSouth Africa

AIM： TO study if T-cell activation related to portasystemic shunting causes osteoclast-mediated bone loss through RANKL-dependent pathways. We also investigated if T-cell inhibition using rapamycin would protect against bone loss in rats. METHODS： Portasystemic shunting was performed in male Sprague-Dawley rats and rapamycin 0.1 mg/kg was administered for 15 wk by gavage. Rats received powderized chow and supplemental feeds to prevent the effects of malnutrition on bone composition. Weight gain and growth was restored after surgery in shunted animals. At termination, biochemical parameters of bone turnover and quantitative bone histology were assessed. Markers of T-cell activation, inflammatory cytokine production, and RANKL-dependent pathways were measured. In addition, the roles of IGF-1 and hypogonadism were investigated. RESULTS： Portasystemic shunting caused low turnover osteoporosis that was RANKL independent. Bone resorbing cytokine levels, including IL-1, IL-6 and TNFα, were not increased in serum and TNFα and RANKL expression were not upregulated in PBMC. Portasystemic shunting increased the circulating CD8＋ T-cell population. Rapamycin decreased the circulating CD8＋ T-cell population, increased CD8＋ CD25＋ T-regulatory cell population and improved all parameters of bone turnover. CONCLUSION： Osteoporosis caused by portasystemic shunting may be partially ameliorated by rapamycin in the rat model of hepatic osteodystrophy.

关键词： osteopenia Liver disease Portasystemic shunting T-lymphocyte Rapamycin

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No evidence of circulating autoantibodies against osteoprotegerin in patients with celiac disease

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World Journal of Gastroenterology 2012年第14期18卷 1622-1627页

作者： Tiziana Larussa Evelina Suraci Immacolata Nazionale Isabella Leone Tiziana Montalcini Ludovico Abenavoli Maria Imeneo Arturo Pujia Francesco Luzza Department of Health Science University of Catanzaro "Magna Graecia"88100 CatanzaroItaly Department of Medical and Surgical Science University of Catanzaro "Magna Graecia"88100 CatanzaroItaly

AIM:To investigate risk factors for low bone mineral density(BMD) in celiac disease(CD) patients,focusing on circulating autoantibodies against osteoprotegerin(OPG).METHODS:Seventy asymptomatic CD adult patients on gluten-free diet(GFD) and harbouring persistent negative CD-related serology were *** risk factors for osteoporosis(e.g.,age,sex,menopausal status,history of fractures,smoke,and body mass index) were checked and BMD was assessed by dual energy X ray *** calcium and parathyroid hormone(PTH) levels were ***-eight patients underwent repeat duodenal *** samples from a selected sub-group of 30 patients,who were also typed for human leukocyte antigen(HLA) DQ2 and DQ8 haplotype,were incubatedwith homodimeric recombinant human OPG and tested by western blotting with an anti-OPG antibody after ***:Despite persistent negative CD-related serology and strict adherence to GFD,49 out of the 70(74%) patients displayed low *** these patients,13(24%) showed osteoporosis and 36(76%) *** the exception of age,conventional risk factors for osteoporosis did not differ between patients with normal and low *** serum calcium and PTH levels were normal in all *** mucosa healing was found in 31(82%) out of 38 patients who underwent repeat duodenal biopsy with 20(64%) still displaying low *** remaining 7 patients had an incomplete normalization of duodenal mucosa with 6(84%) showing low *** evidence of circulating antibodies against OPG was found in the serum of 30 celiac patients who were tested for,independent of BMD,duodenal histology,and HLA ***:If any,the role of circulating autoantibodies against OPG in the pathogenesis of bone derangement in patients with CD is not a major one.

关键词： Celiac disease Osteoprotegerin Bone mineral density Gluten-free diet Osteoporosis osteopenia

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