RESUMO
Objective: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role. Methods: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship. Results: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio (OR) > 1.5, p < 0.001]. Steiger's test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship. Conclusion: This study's findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis.
Assuntos
Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Osteoporose , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Osteoporose/metabolismo , Osteoporose/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Massa Corporal , Idoso , Circunferência da Cintura , Obesidade/complicações , Obesidade/metabolismo , Relação Cintura-QuadrilRESUMO
Background: Osteoporosis (OP) associated with aging exerts substantial clinical and fiscal strains on societal structures. An increasing number of research studies have suggested a bidirectional relationship between circulating inflammatory markers (CIMs) and OP. However, observational studies are susceptible to perturbations in confounding variables. In contrast, Mendelian randomization (MR) offers a robust methodological framework to circumvent such confounders, facilitating a more accurate assessment of causality. Our study aimed to evaluate the causal relationships between CIMs and OP, identifying new approaches and strategies for the prevention, diagnosis and treatment of OP. Methods: We analyzed publicly available GWAS summary statistics to investigate the causal relationships between CIMs and OP. Causal estimates were calculated via a systematic analytical framework, including bidirectional MR analysis and Bayesian colocalization analysis. Results: Genetically determined levels of CXCL11 (OR = 0.91, 95% CI = 0.85-0.98, P = 0.008, PFDR = 0.119), IL-18 (OR = 0.88, 95% CI = 0.83-0.94, P = 8.66×10-5, PFDR = 0.008), and LIF (OR = 0.86, 95% CI = 0.76-0.96, P = 0.008, PFDR = 0.119) were linked to a reduced risk of OP. Conversely, higher levels of ARTN (OR = 1.11, 95% CI = 1.02-1.20, P = 0.012, PFDR = 0.119) and IFNG (OR = 1.16, 95% CI = 1.03-1.30, P = 0.013, PFDR = 0.119) were associated with an increased risk of OP. Bayesian colocalization analysis revealed no evidence of shared causal variants. Conclusion: Despite finding no overall association between CIMs and OP, five CIMs demonstrated a potentially significant association with OP. These findings could pave the way for future mechanistic studies aimed at discovering new treatments for this disease. Additionally, we are the first to suggest a unidirectional causal relationship between ARTN and OP. This novel insight introduces new avenues for research into diagnostic and therapeutic strategies for OP.
Assuntos
Biomarcadores , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteoporose , Humanos , Osteoporose/sangue , Osteoporose/genética , Osteoporose/etiologia , Osteoporose/diagnóstico , Biomarcadores/sangue , Teorema de Bayes , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Inflamação/sangue , Inflamação/genética , FemininoRESUMO
BACKGROUND: Increasing evidence shows the pivotal significance of miRNAs in the pathogenesis of osteoporosis. miR-381-3p has been identified as an inhibitor of osteogenesis. This study explored the role and mechanism of miR-381-3p in postmenopausal osteoporosis (PMOP), the most common type of osteoporosis. METHODS: Bilateral ovariectomy (OVX) rat model was established and miR-381-3p antagomir was administrated through the tail vein in vivo. The pathological changes in rats were assessed through the evaluation of serum bone turnover markers (BALP, PINP, and CTX-1), hematoxylin and eosin (H&E) staining, as well as the expression of osteoblast differentiation biomarkers. Moreover, isolated bone marrow mesenchymal stem cells from OVX-induced rats (OVX-BMMSCs) were utilized to explore the impact of miR-381-3p on osteoblast differentiation. In addition, the target gene and downstream pathway of miR-381-3p were further investigated both in vivo and in vitro. RESULTS: miR-381-3p expression was elevated, whereas KLF5 was suppressed in OVX rats. miR-381-3p antagomir decreased serum levels of bone turnover markers, improved trabecular separation, promoted osteoblast differentiation biomarker expression in OVX rats. ALP activity and mineralization were suppressed, and levels of osteoblast differentiation biomarkers were impeded after miR-381-3p overexpression during osteoblast differentiation of OVX-BMMSCs. While contrasting results were found after inhibition of miR-381-3p. miR-381-3p targets KLF5, negatively affecting its expression as well as its downstream Wnt/ß-catenin pathway, both in vivo and in vitro. Silencing of KLF5 restored Wnt/ß-catenin activation induced by miR-381-3p antagomir. CONCLUSION: miR-381-3p aggravates PMOP by inhibiting osteogenic differentiation through targeting KLF5/Wnt/ß-catenin pathway. miR-381-3p appears to be a promising candidate for therapeutic intervention in PMOP.
Assuntos
Diferenciação Celular , Fatores de Transcrição Kruppel-Like , MicroRNAs , Osteogênese , Osteoporose Pós-Menopausa , Ovariectomia , Ratos Sprague-Dawley , Via de Sinalização Wnt , Animais , MicroRNAs/genética , Ovariectomia/efeitos adversos , Osteogênese/genética , Osteogênese/fisiologia , Feminino , Via de Sinalização Wnt/fisiologia , Via de Sinalização Wnt/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Ratos , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/metabolismo , Modelos Animais de Doenças , Osteoblastos/metabolismo , Osteoporose/genética , Osteoporose/etiologia , Osteoporose/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células Cultivadas , HumanosRESUMO
BACKGROUND: Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. METHODS: Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. RESULTS: After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. CONCLUSIONS: The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.
Assuntos
Diferenciação Celular , NF-kappa B , Osteoclastos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Fator 6 Associado a Receptor de TNF , Animais , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/genética , Osteoclastos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Feminino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Camundongos , Células RAW 264.7 , Flavonoides/farmacologia , Osteogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Osteoporose/metabolismo , Osteoporose/etiologia , Ovariectomia/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacosRESUMO
Background: While previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear. Objective: Our study used linkage disequilibrium scores(LDSC) regression analysis and Mendelian randomization(MR) to assess the genetic correlation and causal relationship between IBD and OP in European and East Asian populations. Methods: We performed separate genetic correlation and causal analyses for IBD and OP in European and East Asian populations, used the product of coefficients method to estimate the mediating effect of nutritional status on the causal relationship, and used multi-trait analysis to explore the biological mechanisms underlying the IBD-nutrition-OP causal pathway. Results: Our analysis revealed a significant genetic correlation and causal relationship between IBD and OP in the European population. Conversely, no such correlation or causal relationship was observed in the East Asian population. Mediation analysis revealed a significant mediating effect of nutritional status on the causal pathway between IBD and OP in the European population. Multi-trait analysis of the IBD-nutrition-OP causal pathway identified MFAP2, ATP13A2, SERPINA1, FTO and VCAN as deleterious variants. Conclusion: Our findings establish a genetic correlation and causal relationship between IBD and OP in the European population, with nutritional status playing a crucial mediating role.
Assuntos
Povo Asiático , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais , Análise da Randomização Mendeliana , Estado Nutricional , Osteoporose , Polimorfismo de Nucleotídeo Único , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/epidemiologia , Osteoporose/genética , Osteoporose/etiologia , Osteoporose/epidemiologia , Povo Asiático/genética , Desequilíbrio de Ligação , População Branca/genética , Europa (Continente)/epidemiologia , Ásia Oriental/epidemiologia , Feminino , Estudo de Associação Genômica Ampla , Masculino , População do Leste AsiáticoRESUMO
BACKGROUND: Artesunate (ART) has the potential to modulate the nuclear factor kappa B (NF-κB) and Notch1/Hes1 signaling pathways, which play crucial roles in the pathogenesis of osteoporosis. This study aims to explore whether ART participates in the progression of osteoporosis by regulating these signaling pathways. METHODS: In the in vitro experiments, we treated bone marrow mesenchymal stem cells (BMSCs) with different concentrations of ART (0, 3, 6, 12 µM) and evaluated osteogenic differentiation using alkaline phosphatase staining (ALP) and alizarin red S staining (ARS) staining. The expression levels of osteocalcin (OCN), RUNT-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), and receptor activator of the nuclear factor kappa ligand (RANKL) were detected by real-time quantitative PCR (RT-qPCR). The effects of ART on NF-κB p65 and Notch1 protein expression were analyzed by Western blot (WB) and immunofluorescence (IF). In the in vivo experiments, a postmenopausal osteoporosis rat model was established via ovariectomy. Bone tissue pathological injury was evaluated using hematoxylin eosin (HE) staining. Serum ALP levels were measured using a kit, bone density was determined by dual-energy X-ray absorptiometry, and serum levels of bone gla protein (BGP), OPG, RANKL, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and IL-1ß were measured by enzyme-linked immunosorbent assay (ELISA). Additionally, the expression of NF-κB p65 and Notch1 in tissues was assessed by immunohistochemistry. RESULTS: In vitro experiments revealed that compared to the control group, ART dose-dependently promoted BMSCs proliferation and enhanced their osteogenic differentiation capability. The expression of OCN, RUNX2, and OPG significantly increased in the ART-treated group, while RANKL expression decreased significantly (p < 0.05). ART significantly inhibited the expression of NF-κB p65 and Notch1/Hes1 signaling pathway proteins (p < 0.05). Compared to ART treatment alone, combined treatment with ART and phorbol myristate acetate (PMA) or valproic acid (VPA) resulted in increased expression of NF-κB p65 and Notch1 proteins and decreased osteogenic differentiation capability (p < 0.05). In vivo experiments showed that in rats treated with ART, bone damage was significantly reduced, bone density and mineral content were restored considerably, and the expression of inflammatory factors (TNF-α, IL-6, IL-1ß) decreased significantly (p < 0.05). Additionally, ART treatment significantly reduced the expression of NF-κB p65 and Notch1 proteins, increased OPG expression, and decreased BGP and RANKL levels (p < 0.05). CONCLUSION: In summary, ART facilitates the osteogenic differentiation of BMSCs by inhibiting the NF-κB and Notch1/Hes1 signaling pathways, thereby exerting significant protective effects against osteoporosis.
Assuntos
Artesunato , NF-kappa B , Osteoporose , Ovariectomia , Ratos Sprague-Dawley , Receptor Notch1 , Transdução de Sinais , Animais , Artesunato/farmacologia , Artesunato/uso terapêutico , Feminino , Transdução de Sinais/efeitos dos fármacos , Receptor Notch1/metabolismo , NF-kappa B/metabolismo , Osteoporose/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Ratos , Osteogênese/efeitos dos fármacos , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Inflamação/metabolismo , Diferenciação Celular/efeitos dos fármacos , Fatores de Transcrição HES-1RESUMO
BACKGROUND: Osteoporosis is a considerable public health challenge in Moyu County, Xinjiang. Here, we evaluated the influencing factors of osteoporosis in this region. METHODS: We recruited 7,761 participants and randomized them into normal and osteoporotic populations based on T-score. The effects of general conditions, body composition, calcium sources and exercise, respiratory exposure, and daily diet on osteoporosis were analyzed. Furthermore, a structural equation model was constructed to uncover the direct and indirect influencing factors of osteoporosis. RESULTS: Among the participants, 1,803 (23.23%) had normal bone mass while 1,496 (19.28%) had osteoporosis. The univariate analysis showed significant differences in the general conditions, body composition, calcium sources and exercise, respiratory exposure, and daily diet. Stratification based on age (45 years) and body mass index (BMI) (18.5 kg/m2) showed variations in the body composition between the two groups; however, the visceral fat differed significantly. Logistic regression analysis affirmed the association of visceral fat index as it was included in all equations, except for age and female menopause. The structural equation exhibited that the general conditions, body composition, and, calcium sources, and exercise were direct factors of osteoporosis, while respiratory exposure and daily diet were indirect factors. The standardized path coefficient was highest in general conditions, followed by body composition, and lastly, calcium sources and exercise. CONCLUSION: Obesity, besides age and female menopause, is also an influencing factor of osteoporosis. The visceral fat index plays a vital role in osteoporosis. Our findings may provide experimental evidence for early prevention and treatment of osteoporosis.
Assuntos
Gordura Intra-Abdominal , Osteoporose , Humanos , Osteoporose/epidemiologia , Osteoporose/etiologia , Pessoa de Meia-Idade , Feminino , Masculino , Gordura Intra-Abdominal/metabolismo , Idoso , Exercício Físico/fisiologia , Composição Corporal/fisiologia , Índice de Massa Corporal , Adulto , China/epidemiologia , Fatores de RiscoRESUMO
The objective of this review is to examine the connection between osteoporosis and diabetes, compare the underlying causes of osteoporosis in various forms of diabetes, and suggest optimal methods for diagnosing and assessing fracture risk in diabetic patients. This narrative review discusses the key factors contributing to the heightened risk of fractures in individuals with diabetes, as well as the shared elements impacting the treatment of both diabetes mellitus and osteoporosis. Understanding the close link between diabetes and a heightened risk of fractures is crucial in effectively managing both conditions. There are several review articles of meta-analysis regarding diaporosis. Nevertheless, no review articles showed collected and well-organized medications of antidiabetics and made for inconvenient reading for those who were interested in details of drug mechanisms. In this article, we presented collected and comprehensive charts of every antidiabetic medication which was linked to fracture risk and indicated plausible descriptions according to research articles.
Assuntos
Hipoglicemiantes , Osteoporose , Humanos , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Hipoglicemiantes/uso terapêutico , Fraturas Ósseas/etiologia , Diabetes Mellitus , Densidade Óssea , Complicações do Diabetes , Fatores de RiscoRESUMO
BACKGROUND: Early-onset osteoporosis is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT). It remains unknown if physical training can improve bone formation in these patients, as the transplantation procedure may cause sustained dysregulation of the bone-forming osteoblast progenitor cells. OBJECTIVE: We aimed to explore the effect of resistance training on bone remodeling in long-term survivors of pediatric HSCT. PROCEDURE: In this prospective, controlled intervention study, we included seven HSCT survivors and 15 age- and sex-matched healthy controls. The participants completed a 12-week heavy load, lower extremity resistance training intervention with three weekly sessions. We measured fasting serum levels of the bone formation marker "N-terminal propeptide of type I procollagen" (P1NP), and the bone resorption marker "C-terminal telopeptide of type I collagen" (CTX). The hypothesis was planned before data collection began. The trial was registered at Clinicaltrials.gov before including the first participant, with trial registration no. NCT04922970. RESULTS: Resistance training led to significantly increased levels of fasting P1NP in both patients (from 57.62 to 114.99 ng/mL, p = .03) and controls (from 66.02 to 104.62 ng/mL, p < .001). No significant changes in fasting CTX levels were observed. CONCLUSIONS: Despite previous high-dose cytotoxic therapy, long-term survivors of pediatric HSCT respond to resistance training with improvement of bone formation, comparable to that of healthy controls. This suggests that resistance training might be a promising non-pharmacological approach to prevent the early decline in bone mass, and should be considered as part of a follow-up program to counteract long-term sequela after pediatric HSCT.
Assuntos
Remodelação Óssea , Transplante de Células-Tronco Hematopoéticas , Treinamento Resistido , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Criança , Adolescente , Estudos Prospectivos , Sobreviventes , Estudos de Casos e Controles , Seguimentos , Pró-Colágeno/sangue , Fragmentos de Peptídeos/sangue , Osteoporose/etiologia , Colágeno Tipo I/sangue , Biomarcadores/sangueRESUMO
CONTEXT: There is an increasing population of childhood cancer survivors (CCS) at risk for treatment-related toxicities, including skeletal morbidities. Bone mineral density (BMD) is a proxy for bone health and reductions are associated with osteoporosis and fractures. OBJECTIVE: To investigate bone health in CCS by conducting a systematic review and meta-analysis of BMD after completed treatments. DATA SOURCES: We searched Medline, Embase, Cochrane, and Web of Science in May 2019 and updated in May 2023. STUDY SELECTION: Studies reporting BMD Z-scores measured with dual-energy x-ray absorptiometry in CCS after treatment completion. DATA EXTRACTION: We performed a pooled analysis of studies reporting BMD Z-scores and thereafter we analyzed studies comparing BMD in survivors and healthy controls. All analyses were performed based on the site of BMD measurement. RESULTS: Of 4243 studies, 84 were included (N = 8106). The mean time off-treatment across the studies ranged from 2 months to 24 years. The overall pooled mean Z-score was -0.57 (95% confidence interval [CI] -0.59 to -0.55) in the whole-body, -0.84 (95% CI -0.86 to -0.83) in the lumbar spine, -0.79 (95% CI -0.81 to -0.77) in the femoral neck and -0.14 (95% CI -0.18 to -0.11) in the total hip. When comparing survivors with controls, BMD was significantly lower in survivors at all sites. LIMITATIONS: English publications, study-level meta-analysis. CONCLUSIONS: We showed a significant reduction of BMD Z-scores in CCS. Given the increased fracture risk already within -1 SD, these results emphasize the need for BMD surveillance and secondary prevention in CCS.
Assuntos
Densidade Óssea , Sobreviventes de Câncer , Neoplasias , Humanos , Criança , Osteoporose/epidemiologia , Osteoporose/etiologia , Absorciometria de Fóton , AdolescenteRESUMO
BACKGROUND: Previous studies have shown that the inflammatory potential of the diet is associated with a variety of chronic noncommunicable diseases characterized by a chronic low-grade inflammatory response. However, the relationships between dietary inflammatory potential and organismal inflammatory status and osteoporosis have been less studied. This study aimed to investigate the relationships among inflammatory diet, inflammatory state and osteoporosis in the Xinjiang multiethnic population. METHODS: The participants consisted of 4452 adults aged 35 to 74 years from Xinjiang, China. The dietary inflammatory index (DII) was calculated using dietary data collected with a semiquantitative food frequency questionnaire, and information about osteoporosis was derived from quantitative ultrasound measurements. The relationships of the DII score and inflammatory factors with the risk of osteoporosis were analysed using multivariate logistic regression, and the nonlinear associations between DII and osteoporosis were further analysed using restricted cubic splines. RESULTS: The results showed that proinflammatory diets were associated with a greater risk of osteoporosis (T3 vs. T1: OR = 1.87; 95% CI = 1.44, 2.45) and that there was no nonlinear relationship between the DII and the risk of osteoporosis. Increased concentrations of the inflammatory factors IL-6, IL-10, IL-12p70, IL-17, and IL-23 were associated with a greater risk of osteoporosis. CONCLUSIONS: The risk of osteoporosis can be reduced by increasing the consumption of an appropriate anti-inflammatory diet.
Assuntos
Dieta , Inflamação , Osteoporose , Humanos , Pessoa de Meia-Idade , Osteoporose/etiologia , Osteoporose/epidemiologia , Osteoporose/sangue , Feminino , Masculino , Estudos Transversais , China/epidemiologia , Idoso , Adulto , Dieta/efeitos adversos , Inflamação/sangue , Inflamação/etiologia , Fatores de RiscoRESUMO
This article reviews bone metabolism, bone mass, and bone structure changes expected during and after pregnancy and lactation, as well as the condition of pregnancy and lactation-associated osteoporosis (PLO)-a presentation with fragility fracture(s) in the context of these physiologic changes. Clinical implications of physiologic bone changes will be addressed, as will specific management considerations that apply to premenopausal women with PLO.
Assuntos
Densidade Óssea , Osso e Ossos , Lactação , Osteoporose , Complicações na Gravidez , Humanos , Feminino , Gravidez , Lactação/fisiologia , Osteoporose/etiologia , Osteoporose/metabolismo , Densidade Óssea/fisiologia , Osso e Ossos/metabolismo , Osso e Ossos/fisiopatologia , Complicações na Gravidez/fisiopatologiaRESUMO
BACKGROUND: To aim of this study is to assess the mechanism through which Desertliving Cistanche modulates the PI3K/AKT signaling pathway in the treatment of hyperlipidemic osteoporosis in ovariectomized rats. METHODS: We randomly assigned specific-pathogen-free (SPF) rats into five groups (n = 10 per group). The normal control group received a standard diet, while the model group, atorvastatin group, diethylstilbestrol group, and treatment group were fed a high-fat diet. Four weeks later, bilateral ovariectomies were conducted, followed by drug interventions. After six weeks of treatment, relevant indicators were compared and analyzed. RESULTS: Compared to the normal control group, rats in the model group exhibited blurred trabecular morphology, disorganized osteocytes, significantly elevated levels of bone-specific alkaline phosphatase (BALP), bone Gla-protein (BGP), total cholesterol (TC), tumor necrosis factor-α (TNF-α), and receptor activator of NF-κB ligand (RANKL). Also, the model group revealed significantly reduced levels of ultimate load, fracture load, estradiol (E2), bone mineral density (BMD), osteoprotegerin (OPG), and phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in femoral tissue. The atorvastatin group presented with higher TC and TNF-α levels compared to the normal control group. Conversely, the treatment group demonstrated enhanced trabecular morphology, denser structure, smaller bone marrow cavities, and reduced BALP, BGP, TC, TNF-α, and RANKL levels. Furthermore, the treatment group exhibited higher levels of E2, BMD, OPG, and PI3K and Akt in bone tissue compared to the model group. The treatment group also had lower TC and TNF-α levels than the atorvastatin group. Biomechanical analysis indicated that after administration of Desertliving Cistanche, the treatment group had reduced body mass, increased ultimate and fracture load of the femur, denser bone structure, smaller bone marrow cavities, and altered periosteal arrangement compared to the model group. CONCLUSION: Our study revealed that Desertliving Cistanche demonstrated significant efficacy in preventing and treating postmenopausal hyperlipidemic osteoporosis in rats.
Assuntos
Cistanche , Hiperlipidemias , Osteoporose , Ovariectomia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Ovariectomia/efeitos adversos , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Hiperlipidemias/complicações , Hiperlipidemias/metabolismo , Osteoporose/etiologia , Osteoporose/metabolismo , Ratos , Ratos Sprague-Dawley , Densidade Óssea/efeitos dos fármacos , Distribuição AleatóriaRESUMO
Background: A common complication of thalassemia is secondary osteoporosis. This study aimed to assess the prevalence and factors associated with low BMD in thalassemic patients. Method: This is a cross-sectional study. Eligible patients were males aged within 18-49 years or premenopausal women diagnosed with thalassemia in Chiang Mai University Hospital between July 2021 and July 2022. The diagnosis of low BMD by dual-energy x-ray absorptiometry (DXA) was defined as a Z-score of -2.0 SD or lower in either the lumbar spine or femoral neck. Clinical factors associated with low BMD were analyzed using a logistic regression model. Results: Prevalence of low BMD was 62.4% from 210 patients with a mean age of 29.7 ± 7.6 years. The predominant clinical characteristics of low BMD thalassemia patients were being female, transfusion-dependent (TDT) and a history of splenectomy. From multivariable analysis, the independent variables associated with low BMD were transfusion dependency (odds ratio, OR 2.36; 95%CI 1.28 to 4.38; p=0.006) and body mass index (BMI) (OR 0.71; 95%CI 0.61 to 0.82; p<0.001). Among patients with low BMD, we observed a correlation between a Z-score with low IGF-1 levels (ß=-0.42; 95% CI -0.83 to -0.01; p=0.040), serum phosphate levels (ß=0.40; 95% CI 0.07 to 0.73; p=0.016) and hypogonadism (ß=-0.48, 95% CI -0.91 to -0.04, p=0.031). Conclusion: This study found a prevalence of low BMD in 62.4% of subjects. Factors associated with low BMD were TDT and BMI. Within the low BMD subgroup, hypogonadism, serum phosphate and low serum IGF-1 levels were associated with a lower Z-score.
Assuntos
Densidade Óssea , Talassemia , Humanos , Masculino , Feminino , Adulto , Estudos Transversais , Talassemia/epidemiologia , Talassemia/complicações , Talassemia/sangue , Prevalência , Fatores de Risco , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/etiologia , Absorciometria de FótonRESUMO
Abnormalities in osteoclastic generation or activity disrupt bone homeostasis and are highly involved in many pathologic bone-related diseases, including rheumatoid arthritis, osteopetrosis, and osteoporosis. Control of osteoclast-mediated bone resorption is crucial for treating these bone diseases. However, the mechanisms of control of osteoclastogenesis are incompletely understood. In this study, we identified that inosine 5'-monophosphate dehydrogenase type II (Impdh2) positively regulates bone resorption. By histomorphometric analysis, Impdh2 deletion in mouse myeloid lineage cells (Impdh2LysM-/- mice) showed a high bone mass due to the reduced osteoclast number. qPCR and western blotting results demonstrated that the expression of osteoclast marker genes, including Nfatc1, Ctsk, Calcr, Acp5, Dcstamp, and Atp6v0d2, was significantly decreased in the Impdh2LysM-/- mice. Furthermore, the Impdh inhibitor MPA treatment inhibited osteoclast differentiation and induced Impdh2-cytoophidia formation. The ability of osteoclast differentiation was recovered after MPA deprivation. Interestingly, genome-wide analysis revealed that the osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation, were impaired in the Impdh2LysM-/- mice. Moreover, the deletion of Impdh2 alleviated ovariectomy-induced bone loss. In conclusion, our findings revealed a previously unrecognized function of Impdh2, suggesting that Impdh2-mediated mechanisms represent therapeutic targets for osteolytic diseases.
Assuntos
IMP Desidrogenase , Mitocôndrias , Osteoclastos , Osteogênese , Osteoporose , Ovariectomia , Fosforilação Oxidativa , Animais , Osteoporose/metabolismo , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/patologia , Camundongos , Feminino , Osteoclastos/metabolismo , Osteoclastos/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , IMP Desidrogenase/metabolismo , IMP Desidrogenase/genética , IMP Desidrogenase/deficiência , Camundongos Knockout , Camundongos Endogâmicos C57BL , Diferenciação Celular , Reabsorção Óssea/metabolismo , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Reabsorção Óssea/etiologiaRESUMO
Low bone mineral density (BMD) is common in adults with coeliac disease (CD), even in individuals adhering to a gluten-free diet (GFD). Women are more likely to have low BMD and have an increased risk of osteoporosis, so women with pre-existing low BMD related to CD are at an even higher risk. BMD assessed by dual X-ray absorptiometry (DXA) and bone quality assessed through quantitative ultrasound (QUS) were investigated in 31 premenopausal women with CD consuming a GFD, and 39 matched healthy controls from the Lower North Island, New Zealand. In addition, bone metabolism and nutrient status were assessed, and four-day diet diaries were used to estimate nutrient intake. No statistically significant differences were found in BMD assessed by DXA between the two groups at the hip, lumbar spine or forearm. However, the parameters measured by the QUS were significantly lower in CD participants. Dietary data indicated significantly lower intakes of energy, dietary fibre, magnesium and phosphorus in women with CD, likely as a result of a reduced intake of wholegrain foods, and suggested that both groups had inadequate intake of calcium. No significant differences were demonstrated in biochemical parameters. BMD and bone biomarkers indicated no differences between coeliac and healthy women in New Zealand. However, these findings suggest that QUS may be more sensitive for the coeliac population, due to the disease's affect on the trabecular bone, and warrant further research.
Assuntos
Absorciometria de Fóton , Densidade Óssea , Doença Celíaca , Dieta Livre de Glúten , Pré-Menopausa , Humanos , Doença Celíaca/dietoterapia , Doença Celíaca/complicações , Doença Celíaca/fisiopatologia , Feminino , Adulto , Nova Zelândia , Pessoa de Meia-Idade , Osteoporose/etiologia , Estudos de Casos e Controles , Estado Nutricional , Ultrassonografia , Osso e Ossos/metabolismo , Adulto Jovem , Biomarcadores/sangueRESUMO
The relationship between bone mineral density and type 2 diabetes is still controversial. The aim of this study is to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in elderly men and postmenopausal women. The participants in this study included 692 postmenopausal women and older men aged ≥ 50 years, who were divided into the T2DM group and non-T2DM control group according to whether or not they had T2DM. The data of participants in the two groups were collected from the inpatient medical record system and physical examination center systems, respectively, of the Tertiary Class A Hospital. All data analysis is performed in SPSS Software. Compared with all T2DM group, the BMD and T scores of lumbar spines 1-4 (L1-L4), left femoral neck (LFN) and all left hip joints (LHJ) in the non-T2DM group were significantly lower than those in the T2DM group (P < 0.05), and the probability of major osteoporotic fracture in the next 10 years (PMOF) was significantly higher than that in T2DM group (P < 0.001). However, with the prolongation of the course of T2DM, the BMD significantly decreased, while fracture risk and the prevalence of osteoporosis significantly increased (P < 0.05). We also found that the BMD of L1-4, LFN and LHJ were negatively correlated with homeostatic model assessment-insulin resistance (HOMA-IR) (P = 0.028, P = 0.01 and P = 0.047, respectively). The results also showed that the BMD of LHJ was positively correlated with indirect bilirubin (IBIL) (P = 0.018). Although the BMD was lower in the non-T2DM group than in the T2DM group, the prolongation of the course of T2DM associated with the lower BMD. And the higher prevalence of osteoporosis and fracture risk significantly associated with the prolongation of the course of T2DM. In addition, BMD was significantly associated with insulin resistance (IR) and bilirubin levels in T2DM patients.Registration number: China Clinical Trials Registry: MR-51-23-051741; https://www.medicalresearch.org.cn/search/research/researchView?id=c0e5f868-eca9-4c68-af58-d73460c34028 .
Assuntos
Densidade Óssea , Diabetes Mellitus Tipo 2 , Pós-Menopausa , Humanos , Diabetes Mellitus Tipo 2/complicações , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Vértebras Lombares/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/etiologia , Colo do Fêmur/diagnóstico por imagem , Fatores de Risco , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , PrevalênciaRESUMO
Diabetic osteoporosis is a common health problem that is associated with a disruption in bone metabolism. A2A adenosine receptor (A2AAR) signaling seems to play a critical role in bone homeostasis. This study aimed to evaluate the effect of A2AAR stimulation on the treatment of diabetic-induced osteoporosis versus insulin treatment. Forty adult male rats were allocated into control (C), untreated diabetic-induced osteoporosis (DIO), insulin-treated DIO (I-DIO), and A2AAR agonist-treated DIO (A-DIO) groups. Both insulin and A2AAR agonist treatments significantly increased serum insulin level, glutathione peroxidase (GPx) activity, bone expression of osteoprotegerin (Opg) and ß-catenin (Ctnnb1), and cortical and trabecular bone thickness, whereas they decreased serum fasting glucose, malondialdehyde (MDA), tumor necrosis factor α (TNF-α), bone expression of receptor activator of nuclear factor kappa-B ligand (Rankl), runt-related transcription factor-2 (Runx2), and sclerostin (Sost) versus the untreated DIO groups. A2AAR agonist treatment was more effective than insulin in ameliorating diabetic osteoporosis. This might be attributed to the upregulation of ß-catenin gene expression, enhancing its anabolic effect on bone, in addition to the A2AAR agonist's anti-oxidative, anti-inflammatory, and anti-diabetic effects.
Assuntos
Diabetes Mellitus Experimental , Osteoporose , Animais , Masculino , Ratos , Agonistas do Receptor A2 de Adenosina/farmacologia , Agonistas do Receptor A2 de Adenosina/uso terapêutico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Insulina/metabolismo , Osteoporose/metabolismo , Osteoporose/etiologia , Osteoporose/tratamento farmacológico , Ratos Wistar , Receptor A2A de Adenosina/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: Bone mesenchymal stem cells (BMSCs) have been tentatively applied in the treatment of glucocorticoid-induced osteoporosis (GIOP) and systemic lupus erythematosus (SLE). However, the effects of BMSCs on osteoporosis within the context of glucocorticoid (GC) application in SLE remain unclear. Our aim was to explore the roles of BMSCs and different doses of GC interventions on osteoporosis in SLE murine models. METHODS: MRL/MpJ-Faslpr mice were divided into eight groups with BMSC treatment and different dose of GC intervention. Three-dimensional imaging analysis and hematoxylin and eosin (H&E) staining were performed to observe morphological changes. The concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in serum were measured by enzyme-linked immunosorbent assay (ELISA). The subpopulation of B cells and T cells in bone marrows and spleens were analyzed by flow cytometry. Serum cytokines and chemokines were assessed using Luminex magnetic bead technology. RESULTS: BMSCs ameliorated osteoporosis in murine SLE models by enhancing bone mass, improving bone structure, and promoting bone formation through increased bone mineral content and optimization of trabecular morphology. BMSC and GC treatments reduced the number of B cells in bone marrows, but the effect was not significant in spleens. BMSCs significantly promoted the expression of IL-10 while reducing IL-18. Moreover, BMSCs exert immunomodulatory effects by reducing Th17 expression and rectifying the Th17/Treg imbalance. CONCLUSION: BMSCs effectively alleviate osteoporosis induced by SLE itself, as well as osteoporosis resulting from SLE combined with various doses of GC therapy. The therapeutic effects of BMSCs appear to be mediated by their influence on bone marrow B cells, T cell subsets, and associated cytokines. High-dose GC treatment exerts a potent anti-inflammatory effect but may hinder the immunotherapeutic potential of BMSCs. Our research may offer valuable guidance to clinicians regarding the use of BMSC treatment in SLE and provide insights into the judicious use of GCs in clinical practice.
Assuntos
Modelos Animais de Doenças , Glucocorticoides , Lúpus Eritematoso Sistêmico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoporose , Animais , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/terapia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Osteoporose/etiologia , Osteoporose/tratamento farmacológico , Osteoporose/terapia , Glucocorticoides/administração & dosagem , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Feminino , Camundongos Endogâmicos MRL lpr , Citocinas/metabolismoRESUMO
For women under age 65, varying recommendations and the need to apply clinical risk calculators can lead to underscreening for osteoporosis. The resulting undertreatment may lead to a risk of osteoporotic fractures with significant morbidity and impact on functional status. Factors that must be considered when deciding to screen a woman under age 65 include a history of fragility fractures, race, family history, body mass index, smoking, high alcohol use, and secondary causes of osteoporosis. Secondary causes of osteoporosis are much more common in younger women. These include common conditions such as glucocorticoid use, hyperthyroidism, hypogonadism, chronic kidney disease, diabetes, anticonvulsant use, rheumatoid arthritis, malabsorption, and a history of anorexia nervosa. The reasons why these conditions confer an increased risk of osteoporosis are discussed. Recommendations are provided for the clinician to be aware of when screening women under age 65 for osteoporosis and initiating treatment when indicated.