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1.
Commun Biol ; 7(1): 548, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719881

RESUMO

Hyperthyroidism is a well-known trigger of high bone turnover that can lead to the development of secondary osteoporosis. Previously, we have shown that blocking bone morphogenetic protein (BMP) signaling systemically with BMPR1A-Fc can prevent bone loss in hyperthyroid mice. To distinguish between bone cell type-specific effects, conditional knockout mice lacking Bmpr1a in either osteoclast precursors (LysM-Cre) or osteoprogenitors (Osx-Cre) were rendered hyperthyroid and their bone microarchitecture, strength and turnover were analyzed. While hyperthyroidism in osteoclast precursor-specific Bmpr1a knockout mice accelerated bone resorption leading to bone loss just as in wildtype mice, osteoprogenitor-specific Bmpr1a deletion prevented an increase of bone resorption and thus osteoporosis with hyperthyroidism. In vitro, wildtype but not Bmpr1a-deficient osteoblasts responded to thyroid hormone (TH) treatment with increased differentiation and activity. Furthermore, we found an elevated Rankl/Opg ratio with TH excess in osteoblasts and bone tissue from wildtype mice, but not in Bmpr1a knockouts. In line, expression of osteoclast marker genes increased when osteoclasts were treated with supernatants from TH-stimulated wildtype osteoblasts, in contrast to Bmpr1a-deficient cells. In conclusion, we identified the osteoblastic BMP receptor BMPR1A as a main driver of osteoporosis in hyperthyroid mice promoting TH-induced osteoblast activity and potentially its coupling to high osteoclastic resorption.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo I , Reabsorção Óssea , Hipertireoidismo , Camundongos Knockout , Osteoblastos , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Osteoblastos/metabolismo , Hipertireoidismo/metabolismo , Hipertireoidismo/genética , Hipertireoidismo/complicações , Camundongos , Reabsorção Óssea/metabolismo , Reabsorção Óssea/genética , Osteoporose/metabolismo , Osteoporose/genética , Osteoporose/etiologia , Osteoporose/patologia , Osteoclastos/metabolismo , Masculino , Diferenciação Celular
2.
Int J Mol Sci ; 25(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732046

RESUMO

Obesity, type 2 diabetes mellitus (T2DM) and osteoporosis are serious diseases with an ever-increasing incidence that quite often coexist, especially in the elderly. Individuals with obesity and T2DM have impaired bone quality and an elevated risk of fragility fractures, despite higher and/or unchanged bone mineral density (BMD). The effect of obesity on fracture risk is site-specific, with reduced risk for several fractures (e.g., hip, pelvis, and wrist) and increased risk for others (e.g., humerus, ankle, upper leg, elbow, vertebrae, and rib). Patients with T2DM have a greater risk of hip, upper leg, foot, humerus, and total fractures. A chronic pro-inflammatory state, increased risk of falls, secondary complications, and pharmacotherapy can contribute to the pathophysiology of aforementioned fractures. Bisphosphonates and denosumab significantly reduced the risk of vertebral fractures in patients with both obesity and T2DM. Teriparatide significantly lowered non-vertebral fracture risk in T2DM subjects. It is important to recognize elevated fracture risk and osteoporosis in obese and T2DM patients, as they are currently considered low risk and tend to be underdiagnosed and undertreated. The implementation of better diagnostic tools, including trabecular bone score, lumbar spine BMD/body mass index (BMI) ratio, and microRNAs to predict bone fragility, could improve fracture prevention in this patient group.


Assuntos
Densidade Óssea , Diabetes Mellitus Tipo 2 , Obesidade , Osteoporose , Humanos , Diabetes Mellitus Tipo 2/complicações , Osteoporose/etiologia , Osteoporose/tratamento farmacológico , Obesidade/complicações , Fraturas Ósseas/etiologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia
3.
J Int Med Res ; 52(5): 3000605241246743, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38698517

RESUMO

OBJECTIVE: To identify patients with type 2 diabetes mellitus (T2DM) with no history of fracture or osteoporosis treatment who are at risk of bone complications through the assessment of bone quality and quantity. METHODS: Of the outpatients attending our clinic during 2021 to 2022, we retrospectively enrolled 137 (men/women: 85/52, median age: 65 years) consecutive patients aged ≥40 years who had T2DM but no history of fracture or osteoporosis treatment. The lumbar spine and femoral neck bone mineral density and the trabecular bone score were determined using dual-energy X-ray absorptiometry. Independent factors associated with bone disease were identified using logistic regression analysis, and odds ratios (ORs) were calculated. RESULTS: Age and female sex were significantly associated with high ORs for development of bone disease. The integrated risk of bone complications was nearly 40-fold higher in older (≥65 years) women than in younger (<65 years) men. This difference remained after adjustment for the duration of T2DM, body mass index, and HbA1c level. CONCLUSIONS: Older women have the highest risk of osteopenia and osteoporosis among patients with T2DM who have no history of fracture or osteoporosis treatment. These patients should undergo intensive monitoring for bone fragility from an early stage of their disease.


Assuntos
Absorciometria de Fóton , Densidade Óssea , Diabetes Mellitus Tipo 2 , Osteoporose , Humanos , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/etiologia , Fatores Sexuais , Estudos Retrospectivos , Fatores Etários , Fatores de Risco , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/epidemiologia , Vértebras Lombares/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/patologia , Índice de Massa Corporal
4.
Front Endocrinol (Lausanne) ; 15: 1298531, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745961

RESUMO

Introduction: The relationship between intervertebral disc degeneration (IVDD) and osteoporosis (OP), diagnosed primarily using bone mineral density (BMD), remains unclear so far. The present study, therefore, aimed to investigate the potential relationship between osteoporosis and intervertebral disc degeneration using Mendelian randomization and genome-wide association analyses. Specifically, the impact of bone mineral density on the development of intervertebral disc degeneration was evaluated. Materials and methods: The genome-wide association studies (GWAS) summary data of OP/BMDs and IVDD were collected from the FinnGen consortium, the GEFOS consortium, and MRC-IEU. The relationship between IVDD and OP was then explored using TSMR. The inverse-variance weighted (IVW) method was adopted as the primary effect estimate, and the reliability and stability of the results were validated using various methods, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. Results: No significant causal relationship was observed between OP and IVDD (IVW, P > 0.05) or between femoral neck BMD (FA-BMD) and IVDD when OP and FA-BMD were used as exposures. However, increased levels of total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD) were revealed as significant risk factors for IVDD (TB-BMD: IVW, OR = 1.201, 95% CI: 1.123-1.284, P = 8.72 × 10-8; LS-BMD: IVW, OR = 1.179, 95% CI: 1.083-1.284, P = 1.43 × 10-4). Interestingly, both heel BMD (eBMD) and femur neck BMD (FN-BMD) exhibited potential causal relationships (eBMD: IVW, OR = 1.068, 95% CI: 1.008-1.131, P = 0.0248; FN-BMD, IVW, OR = 1.161, 95% CI: 1.041-1.295, P = 0.0074) with the risk of IVDD. The reverse MR analysis revealed no statistically causal impact of IVDD on OP and the level of BMD (P > 0.05). Conclusion: OP and the level of FA-BMD were revealed to have no causal relationship with IVDD. The increased levels of TB-BMD and LS-BMD could promote the occurrence of IVDD. Both eBMD and FN-BMD have potential causal relationships with the risk of IVDD. No significant relationship exists between IVDD and the risk of OP. Further research is warranted to comprehensively comprehend the molecular mechanisms underlying the impact of OP and BMD on IVDD and vice versa.


Assuntos
Densidade Óssea , Estudo de Associação Genômica Ampla , Degeneração do Disco Intervertebral , Análise da Randomização Mendeliana , Osteoporose , Humanos , Degeneração do Disco Intervertebral/genética , Densidade Óssea/genética , Osteoporose/genética , Osteoporose/etiologia , Feminino , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Masculino
5.
BMC Musculoskelet Disord ; 25(1): 345, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38693494

RESUMO

BACKGROUND: Educational duration might play a vital role in preventing the occurrence and development of osteoporosis(OP). PURPOSE: To assess the causal effect of educational duration on bone mineral density(BMD) and risk factors for OP by Mendelian randomization(MR) study. METHODS: The causal relationship was analyzed using data from genome-wide association study(GWAS). Inverse variance weighting (IVW) was used as the main analysis method. Horizontal pleiotropy was identified by MR-Egger intercept test, MR pleiotropy residual sum and outlier (MR-PRESSO) test. The leave-one-out method was used as a sensitivity analysis. RESULTS: The IVW results indicated that there was a positive causal relationship between educational duration and BMD (OR = 1.012, 95%CI:1.003-1.022), physical activity(PA) (OR = 1.156, 95%CI:1.032-1.295), calcium consumption (OR = 1.004, 95%CI:1.002-1.005), and coffee intake (OR = 1.019, 95%CI:1.014-1.024). There was a negative association between whole body fat mass (OR = 0.950, 95%CI:0.939-0.961), time for vigorous PA (OR = 0.955, 95%CI:0.939-0.972), sunbath (OR = 0.987, 95%CI:0.986-0.989), salt consumption (OR = 0.965, 95%CI:0.959-0.971), fizzy drink intake (OR = 0.985, 95%CI:0.978-0.992), smoking (OR = 0.969, 95%CI:0.964-0.975), and falling risk (OR = 0.976, 95%CI:0.965-0.987). There was no significant association between educational duration and lean mass, time for light-to-moderate PA, milk intake, and alcohol intake. Horizontal pleiotropy was absent in this study. The results were robust under sensitivity analyses. CONCLUSION: A longer educational duration was causally linked with increased BMD. No causal relationship had been found between educational duration and lean mass, time for light-to-moderate PA, milk intake, and alcohol consumption as risk factors for osteoporosis.


Assuntos
Densidade Óssea , Exercício Físico , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteoporose , Humanos , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/genética , Fatores de Risco , Escolaridade , Fatores de Tempo , Feminino
6.
Endocrinol Metab (Seoul) ; 39(2): 267-282, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38693817

RESUMO

This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.


Assuntos
Transplante de Órgãos , Osteoporose , Humanos , Transplante de Órgãos/efeitos adversos , Osteoporose/etiologia , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Complicações Pós-Operatórias/etiologia
7.
Sao Paulo Med J ; 142(5): e2023266, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655984

RESUMO

BACKGROUND: Osteoporosis, characterized by decreased bone density and increased fracture risk, imposes significant physical, psychosocial, and financial burdens. Early detection and prevention are crucial for managing osteoporosis and reducing the risk of fractures. OBJECTIVES: To investigate the relationship between Hepatitis A seropositivity and bone mineral density (BMD) in adolescents and adults and to explore the potential link between Hepatitis A infection and osteoporosis risk. DESIGN AND SETTING: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 to evaluate the association between hepatitis A seropositivity and BMD in 15,693 participants. METHODS: Multivariable regression analysis was used to calculate the mean BMD and standard error for adolescents and adults, followed by an independent z-test to determine whether there was a significant difference between the seropositive and seronegative groups. RESULTS: Hepatitis A seropositive adolescents and adults had lower BMD than their seronegative counterparts, with significant differences in lumber spine (mean difference = -0.03 g/cm2, P < 0.01 for both age groups) and pelvis BMDs (mean difference = -0.02 g/cm2, P < 0.01 for the adult age groups), after adjusting for various covariates. CONCLUSIONS: This study confirmed that both adolescent and adult individuals seropositive for Hepatitis A antibodies had reduced BMD among both adolescents and adults, especially in the adult group. This finding suggests a possible link between Hepatitis A infection and risk of osteoporosis.


Assuntos
Densidade Óssea , Hepatite A , Inquéritos Nutricionais , Osteoporose , Humanos , Densidade Óssea/fisiologia , Estudos Transversais , Adolescente , Masculino , Feminino , Adulto , Hepatite A/epidemiologia , Osteoporose/sangue , Osteoporose/etiologia , Adulto Jovem , Pessoa de Meia-Idade , Fatores de Risco , Anticorpos Anti-Hepatite A/sangue
8.
Acta Med Indones ; 56(1): 20-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38561882

RESUMO

BACKGROUND: Osteoporosis is a major problem in transfusion-dependent thalassemia patients (TDT) patients. Osteoprotegerin (OPG) is one of several bone markers that are closely associated with osteoporosis in TDT patients. OPG is a glycoprotein that functions as a feedback receptor for the Receptor Activator of Nuclear Factor kappa B Ligand (RANKL), which is an alpha tumor necrosis factor receptor. One of the causes of decreased bone mass density is iron toxicity, which can be identified by showing elevated transferrin saturation. Bone mass dual X-ray absorptiometry (DEXA) is a gold standard for the diagnosis of osteoporosis, these procedures are not commonly available in Indonesia. This study was conducted to analyze the correlation between serum levels of OPG and transferrin saturation in TDT patients. METHODS: A correlational study with a cross-sectional approach analyzed data from TDT patients at Hemato-Oncology Medic Outpatient Clinic, Hasan Sadikin General Hospital, Bandung, Indonesia. Primary data were obtained through blood sampling and anthropometry measurement while secondary data were obtained from the patient's medical records. OPG and transferrin saturation levels were assessed using the ELISA method. Research data were analyzed using the rank Spearman correlation test. RESULTS: Data were collected from 51 research subjects (30 women dan 21 men). The median OPG level was 380 (170-1230) pg/mL and the median transferrin saturation level was 89.4 (66.7 - 96.2)%. Analysis of correlation showed a significant correlation between and transferrin saturation level with a coefficient value of r -0.539 and p-value <0.001. CONCLUSION: There was a significant inverse correlation between OPG with transferrin saturation in TDT patients.


Assuntos
Osteoporose , Talassemia , Masculino , Humanos , Feminino , Osteoprotegerina , Densidade Óssea , Osteoporose/etiologia , Osteoporose/patologia , Talassemia/terapia , Talassemia/complicações , Transferrinas , Ligante RANK
9.
Nutrients ; 16(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674910

RESUMO

Type 2 diabetes mellitus (T2DM) presents a challenge for individuals today, affecting their health and life quality. Besides its known complications, T2DM has been found to contribute to bone/mineral abnormalities, thereby increasing the vulnerability to bone fragility/fractures. However, there is still a need for appropriate diagnostic approaches and targeted medications to address T2DM-associated bone diseases. This study aims to investigate the relationship between changes in gut microbiota, T2DM, and osteoporosis. To explore this, a T2DM rat model was induced by combining a high-fat diet and low-dose streptozotocin treatment. Our findings reveal that T2DM rats have lower bone mass and reduced levels of bone turnover markers compared to control rats. We also observe significant alterations in gut microbiota in T2DM rats, characterized by a higher relative abundance of Firmicutes (F) and Proteobacteria (P), but a lower relative abundance of Bacteroidetes (B) at the phylum level. Further analysis indicates a correlation between the F/B ratio and bone turnover levels, as well as between the B/P ratio and HbA1c levels. Additionally, at the genus level, we observe an inverse correlation in the relative abundance of Lachnospiraceae. These findings show promise for the development of new strategies to diagnose and treat T2DM-associated bone diseases.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Dieta Hiperlipídica , Disbiose , Microbioma Gastrointestinal , Osteoporose , Estreptozocina , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Osteoporose/etiologia , Diabetes Mellitus Experimental/microbiologia , Ratos , Masculino , Diabetes Mellitus Tipo 2/microbiologia , Ratos Sprague-Dawley , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo
10.
Acta Cir Bras ; 39: e391024, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656061

RESUMO

PURPOSE: Osteoporosis is a bone disease which commonly occurred in postmenopausal women. Almost 10 percent of world population and approximately 30% of women (postmenopausal) suffer from this disease. Alternative medicine has great success in the treatment of osteoporosis disease. Bryodulcosigenin, a potent phytoconstituent, already displayed the anti-inflammatory and antioxidant effect. In this study, we made effort to analyze the antiosteoporosis effect of bryodulcosigenin against ovariectomy (OVX) induced osteoporosis in rats. METHODS: Swiss albino Wistar rats were grouped into fIve groups and given an oral dose of bryodulcosigenin (10, 20 and 30 mg/kg) for eight weeks. Body weight, uterus, bone mineral density, cytokines, hormones parameters, transforming growth factor (TGF)-ß, insulin-like growth factor (IGF), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand (RANKL), and its ratio were estimated. RESULTS: Bryodulcosigenin significantly (p < 0.001) suppressed the body weight and enhanced the uterine weight and significantly (p < 0.001) increased the bone mineral density in whole femur, caput femoris, distal femur and proximal femur. Bryodulcosigenin significantly (P < 0.001) altered the level of biochemical parameters at dose dependent manner, significantly (P < 0.001) improved the level of estrogen and suppressed the level of follicle stimulating hormone and luteinizing hormone. Bryodulcosigenin significantly (P < 0.001) improved the level of OPG and suppressed the level of RANKL. CONCLUSIONS: Bryodulcosigenin reduced the cytokines level and suppressed the TGF-ß and IGF. We concluded that bryodulcosigenin is an antiosteoporosis medication based on the findings.


Assuntos
Densidade Óssea , Osteoporose , Ovariectomia , Ratos Wistar , Animais , Feminino , Densidade Óssea/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Osteoporose/etiologia , Ratos , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Útero/efeitos dos fármacos , Citocinas/sangue , Citocinas/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Resultado do Tratamento
11.
PLoS One ; 19(4): e0302566, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38669283

RESUMO

INTRODUCTION: Solid organ transplant (SOT) recipients can experience bone loss caused by underlying conditions and the use of immunosuppressants. As a result, SOT recipients are at risk for decreased bone mineral density (BMD) and increased fracture incidences. We propose a network meta-analysis (NMA) that incorporates all available randomized control trial (RCT) data to provide the most comprehensive ranking of anti-osteoporotic interventions according to their ability to decrease fracture incidences and increase BMD in SOT recipients. METHODS: We will search MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and CNKI for relevant RCTs that enrolled adult SOT recipients, assessed anti-osteoporotic therapies, and reported relevant outcomes. Title and full-text screening as well as data extraction will be performed in-duplicate. We will report changes in BMD as weighted or standardized mean differences, and fracture incidences as risk ratios. SUCRA scores will be used to provide rankings of interventions, and quality of evidence will be examined using RoB2 and CINeMA. DISCUSSIONS: To our knowledge, this systematic review and NMA will be the most comprehensive quantitative analysis regarding the management of bone loss and fractures in SOT recipients. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with SOT. The findings of the NMA will be disseminated in a peer-reviewed journal.


Assuntos
Densidade Óssea , Fraturas Ósseas , Metanálise em Rede , Transplante de Órgãos , Osteoporose , Revisões Sistemáticas como Assunto , Humanos , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Fraturas Ósseas/prevenção & controle , Fraturas Ósseas/etiologia , Transplante de Órgãos/efeitos adversos , Osteoporose/prevenção & controle , Osteoporose/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto/métodos
12.
Biomed Pharmacother ; 174: 116523, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574627

RESUMO

Inflammatory bowel disease is linked to a higher occurrence of bone loss. Oxyberberine can effectively improve experimental inflammatory bowel disease. However, no study has shown the effect of oxyberberine on inflammatory bowel disease induced bone loss. The present study was performed to investigate the role of oxyberberine in inflammatory bowel disease induced osteoporosis in chronic inflammatory bowel disease mice model. The inflammatory bowel disease mice were orally given two doses of oxyberberine daily. Blood, colon, and bone specimens were collected for biomarker assessments and histological examinations. Bone biomechanical properties and key proteins and genes involved in the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway were evaluated. Additionally, the binding characteristics of oxyberberine and receptor activator of nuclear factor kappa-B ligand were evaluated by in silico simulation. Results indicated that oxyberberine treatment significantly attenuated the macroscopic damage, colonic shortening, and histological injury from the colon. Furthermore, oxyberberine decreased serum inflammatory cytokine levels. The intervention with oxyberberine significantly mitigated the deterioration of bone mass, biomechanical properties, and microstructural parameters. Moreover, the upregulated osteoclast formation factors in model mice were significantly abolished by oxyberberine. In silico simulation results also showed that oxyberberine was firmly bound with target protein. Hence, our findings indicated that oxyberberine had the potential to mitigate inflammatory bowel disease induced inflammation in bone, inhibit osteoclast formation through regulating the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway, and might be a valuable approach in preventing bone loss associated with inflammatory bowel disease.


Assuntos
Doenças Inflamatórias Intestinais , NF-kappa B , Osteoporose , Ligante RANK , Transdução de Sinais , Animais , Ligante RANK/metabolismo , Transdução de Sinais/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/metabolismo , Osteoporose/prevenção & controle , NF-kappa B/metabolismo , Camundongos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Berberina/farmacologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Citocinas/metabolismo
13.
Clin Rheumatol ; 43(5): 1421-1433, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499817

RESUMO

Rheumatoid arthritis (RA) and osteoporosis are two chronic disorders that are often seen together. RA is an autoimmune disorder that causes pain and inflammation in the joints, while osteoporosis is a disorder in which the bones become weak and fragile. Risk factors for bone loss in RA include disease activity, longer disease duration, erosive disease, autoantibody positivity, and joint damage leading to impaired physical activity. Recent research has shown that there is a complex interplay between immune cells, cytokines, and bone remodeling processes in both RA and osteoporosis. The bone remodeling process is regulated by cytokines and immune system signaling pathways, with osteoclasts activated through the RANK/RANKL/OPG pathway and the Wnt/DKK1/sclerostin pathway. Understanding these mechanisms can aid in developing targeted therapies for treatment of osteoporosis in RA patients. Current pharmacological approaches include anti-osteoporotic drugs such as bisphosphonates, denosumab, teriparatide, abaloparatide, raloxifene, and romosozumab. Conventional disease-modifying antirheumatic drugs such as methotrexate and biologicals including TNF inhibitors, IL-6 inhibitors, rituximab, and abatacept lower disease activity in RA and can improve bone metabolism by reducing inflammation but have limited impact on bone mineral density. This review will shed light on the relationship between osteoporosis and rheumatoid arthritis as well as the various factors that influence the onset of osteoporosis in RA patients. We also explore several treatment approaches to effectively managing osteoporosis in RA patients.


Assuntos
Antirreumáticos , Artrite Reumatoide , Osteoporose , Humanos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Antirreumáticos/uso terapêutico , Densidade Óssea , Inflamação/complicações
14.
J Mol Med (Berl) ; 102(5): 655-665, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38436712

RESUMO

NOD-like receptor family CARD domain containing 3 (NLRC3) is the intracellular protein belonging to NLR (NOD-like receptor) family. NLRC3 can negatively regulate inflammatory signal transduction pathways within the adaptive and innate immunocytes. However, studies need to elucidate the biological role of NLRC3 in bone remodeling. Herein, our study proved that NLRC3 prevents bone loss by inhibiting TNFα+ Th17 cell responses. In osteoporosis, NLRC3 attenuated TNFα+ Th17 cell accumulation in the bone marrow. However, osteoporosis (OP) development was aggravated without affecting bone marrow macrophage (BMM) osteoclastogenesis in NLRC3-deficient ovariectomized (OVX) mice. In this study, we transferred the wild-type and NLRC3-/- CD4+ cells into Rag1-/- mice. Consequently, we evidenced the effects of NLRC3 in CD4+ T cells on inhibiting the accumulation of TNFα + Th17 cells, thus restricting bone loss in the OVX mice. Simultaneously, NLRC3-/- CD4+ T cells promoted the recruitment of osteoclast precursors and inflammatory monocytes into the OVX mouse bone marrow. Mechanism-wise, NLRC3 reduced the secretion of TNFα + Th17 cells of RANKL, MIP1α, and MCP1, depending on the T cells. In addition, NLRC3 negatively regulated the Th17 osteoclastogenesis promoting functions via limiting the NF-κB activation. Collectively, this study appreciated the effect of NLRC3 on modulating bone mass via adaptive immunity depending on CD4+ cells. According to findings of this study, NLRC3 may be the candidate anti-OP therapeutic target. KEY MESSAGES: NLRC3 negatively regulated the Th17 osteoclastogenesis promoting functions via limiting the NF-κB activation. NLRC3 may be the candidate anti-OP therapeutic target.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular , Osteoclastos , Osteogênese , Osteoporose , Células Th17 , Fator de Necrose Tumoral alfa , Animais , Células Th17/imunologia , Células Th17/metabolismo , Osteoporose/metabolismo , Osteoporose/etiologia , Osteoporose/imunologia , Osteoporose/genética , Camundongos , Fator de Necrose Tumoral alfa/metabolismo , Osteoclastos/metabolismo , Feminino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia
15.
Front Endocrinol (Lausanne) ; 15: 1344376, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524631

RESUMO

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD.


Assuntos
Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Osteoporose , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Diabetes Mellitus Tipo 2/complicações , Fibrose , Neoplasias Hepáticas/complicações , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose/etiologia
16.
Exp Gerontol ; 188: 112392, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447925

RESUMO

BACKGROUND: Osteoporosis is characterized by low bone mass and deterioration of bone tissue, which is influenced by both environmental factors and nutritional metabolism. The relationship between biochemical indicators and bone mineral density (BMD) is intricate and involves complex mechanisms. Path analysis, a statistical method that investigates causal relationships and the strength of associations among multiple factors, can be valuable in elucidating the connection between biochemical indicators and BMD. METHODS: In this study, we employed advanced statistical techniques, specifically structural equation modeling (SEM) to investigate the intricate interrelationships among a myriad of factors that exert influence on BMD. This analytical approach facilitated not only the identification of the direct relationships between specific variables and BMD but also the exploration of the intricate of indirect pathway through which other variables contribute to the oval impact on BMD. By delving into the direct and indirect effects, we aimed to unravel the complex influences that collectively shape the state of bone health, providing a nuanced understanding of the multifaceted nature of the factors affecting BMD. RESULTS: Our findings revealed that lipid levels had a significant indirect influence on BMD, which was mediated by body mass index (BMI). BMI exhibited both direct and indirect effects on BMD. Uric acid (UA) exerted a significant direct and indirect influence on BMD, with glomerular filtration rate (GFR) acting as the mediator. However, the total effect of UA on BMD was not significant due to the cancellation of positive effect UA on BMD but negative indirect effects of UA through GFR. For females, albumin had a significant direct effect on BMD, whereas this effect was not observed in males. The path analysis models generated results that demonstrated an acceptable fit for both female data (χ2 = 9.63, df = 7, p = 0.21, comparative fit index (CFI) = 0.98, root mean square error of approximation (RMSEA) = 0.05) and male data (χ2 = 6.26, df = 4, p = 0.18, CFI = 0.97, RMSEA = 0.06). CONCLUSIONS: Nutritional metabolism plays a crucial role in maintaining BMD in elderly females and males.


Assuntos
Osteoporose , Masculino , Humanos , Feminino , Idoso , Estudos Transversais , Osteoporose/etiologia , Densidade Óssea , Índice de Massa Corporal , Osso e Ossos
17.
Medicine (Baltimore) ; 103(12): e37467, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518020

RESUMO

Previous observational studies have observed a correlation between sedentary behavior and osteoporosis. However, conclusions from these studies have been contradictory. To explore the potential causal relationship between sedentary behavior and osteoporosis, we conducted a Mendelian randomization analysis. A two-sample Mendelian randomization was adopted to explore the causal relationship of leisure sedentary behavior with osteoporosis. We employed 5 methods to estimate the causal associations between leisure sedentary behavior and osteoporosis. Univariable Mendelian randomization results provided evidence for the causal relationship of the time spent on computer-use with the bone mineral density estimated by heel quantitative ultrasound (eBMD) (inverse variance weighted [IVW]: ß (95% confidence interval [CI]) - 0.150 (-0.270 to -0.031), P = .013; weighted median: ß (95%CI) - 0.195 (-0.336 to -0.055), P = .006). Similar associations were observed in the driving forearm bone mineral density (FABMD) (IVW: ß (95%CI) - 0.933 (-1.860 to -0.007), P = .048) and driving lumbar spine bone mineral density (IVW: ß (95%CI) - 0.649 (-1.175 to -0.124), P = .015). However, we did not find a significant causal relationship between the time spent on watching TV and bone mineral density. Research showed that there was a causal relationship between the time spent on computer use and driving time and eBMD, FABMD, and lumbar spine bone mineral density.


Assuntos
Síndrome de Cogan , Osteoporose , Comportamento Sedentário , Humanos , Análise da Randomização Mendeliana , Osteoporose/etiologia , Osteoporose/genética , Densidade Óssea/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único
18.
Medicine (Baltimore) ; 103(12): e37430, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518046

RESUMO

RATIONALE: There is still information about pregnancy- and lactation-associated osteoporosis, which is a type of osteoporosis that occurs in women with normal bone in the late pregnancy or lactation period. PATIENT CONCERNS: Six cases of pregnancy- and lactation-associated osteoporosis diagnosed in our Endocrinology and Orthopedics Departments from January 2018 to June 2020 were retrospectively studied. The baseline characteristics, clinical features, laboratory findings, radiological manifestations, and follow-up outcomes were analyzed and compared with previous reports. DIAGNOSES: All six patients underwent magnetic resonance imaging scans and vertebral compressive fractures were detected in four patients. OUTCOMES: All six patients received conservative treatment and no surgical intervention. After a mean follow-up of 27.3 months (range 24-31 months), the symptoms of the six patients were significantly relieved, although four patients still had low back pain to varying degrees.


Assuntos
Osteoporose , Complicações na Gravidez , Fraturas da Coluna Vertebral , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Densidade Óssea , Osteoporose/etiologia , Osteoporose/tratamento farmacológico , Lactação , Aleitamento Materno , Fraturas da Coluna Vertebral/complicações , Complicações na Gravidez/tratamento farmacológico
19.
Molecules ; 29(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38542877

RESUMO

Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). Nodakenin has been shown to ameliorate osteoporosis; however, its anti-osteoporotic mechanism is unknown. This study aimed to further reveal the mechanism of the anti-osteoporotic action of nodakenin from the perspective of the microbiome and metabolome. An osteoporosis model was induced in mice through ovariectomy (OVX), with bone mass and microstructure assessed using µCT. Subsequently, ELISA and histologic examination were used to detect biochemical indicators of bone conversion and intestinal morphology. Using metabolomics and 16S rRNA sequencing, it was possible to determine the composition and abundance of the gut microbiota in feces. The results revealed that nodakenin treatment improved the bone microstructure and serum levels of bone turnover markers, and increased the intestinal mucosal integrity. 16S rRNA sequencing analysis revealed that nodakenin treatment decreased the relative abundance of Firmicutes and Patescibacteria, as well as the F/B ratio, and elevated the relative abundance of Bacteroidetes in OVX mice. In addition, nodakenin enhanced the relative abundance of Muribaculaceae and Allobaculum, among others, at the genus level. Moreover, metabolomics analysis revealed that nodakenin treatment significantly altered the changes in 113 metabolites, including calcitriol. A correlation analysis revealed substantial associations between various gut microbiota taxa and both the osteoporosis phenotype and metabolites. In summary, nodakenin treatment alleviated OVX-induced osteoporosis by modulating the gut microbiota and intestinal barrier.


Assuntos
Cumarínicos , Microbioma Gastrointestinal , Glucosídeos , Osteoporose , Feminino , Camundongos , Animais , Humanos , RNA Ribossômico 16S/genética , Microbioma Gastrointestinal/genética , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Ovariectomia/efeitos adversos
20.
Rheumatol Int ; 44(5): 757-764, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38488864

RESUMO

This article examines the complex interactions between inflammatory rheumatic diseases (IRDs) and men's health. It delves into the effects of IRDs on reproductive health, erectile dysfunction, prostate involvement, male osteoporosis, body composition, physical activity, and coping mechanisms. The findings show that the prevalence of sexual dysfunction varies among different diseases, underscoring the necessity for comprehensive counseling. The link between IRDs and prostate health, with a substantial rise in benign prostatic hyperplasia among IRD patients, demonstrates the condition's importance. In contrast to popular belief, osteoporosis mostly affects women; the current study highlights the growing identification of male osteoporosis, particularly in the setting of IRDs. Male RA patients had a significant loss in bone mineral density, highlighting the importance of increasing awareness and tailored therapy to address osteoporosis in men. IRDs affect body composition, with male RA patients showing imbalances characterized by decreased lean body mass and increased fat mass. Given the dynamic nature of these conditions, coping with IRDs necessitates thorough and individualized diversified approaches. The complex link between IRDs and men's health demands continuing research, including longitudinal studies and tailored therapies. The essay promotes a patient-centered approach, recognizing the unique obstacles that males with IRDs confront.


Assuntos
Disfunção Erétil , Osteoporose , Doenças Reumáticas , Disfunções Sexuais Fisiológicas , Humanos , Masculino , Feminino , Saúde do Homem , Disfunção Erétil/psicologia , Osteoporose/epidemiologia , Osteoporose/etiologia , Doenças Reumáticas/epidemiologia
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