RESUMEN
BACKGROUND: Osteoporosis (OP) is a common finding in diabetic patients especially high-risk populations such as postmenopausal women. Sclerostin is a glycoprotein chiefly secreted by mature osteocytes and is considered a main regulator of bone formation. The C1q/TNF-Related Protein 3 (CTRP3) was found to be significantly associated with OP in postmenopausal women. The effect of type 2 diabetes mellitus (T2DM) on sclerostin and CTRP3 levels in postmenopausal women is rarely investigated. The present study aimed to assess the impact of T2DM on sclerostin and CTRP3 levels and their relation to OP in postmenopausal women. METHODS: The study included 60 postmenopausal women with T2DM and 60 age-matched postmenopausal non-diabetic women. Bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry (DEXA). Serum levels of sclerostin and CTRP3 were assessed using enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Diabetic group expressed significantly higher serum levels of sclerostin when compared with non-diabetic group (110.0 ± 29.0 versus 51.5 ± 23.2 ng; p < 0.001). Oppositely, CTRP3 were significantly lower in the diabetic group (3.5 ± 3.5 versus 9.9 ± 3.7 ng/ml, p < 0.001). Multivariate logistic regression analysis identified HbA1c levels [OR (95% CI): 0.49 (0.26-0.93), p = 0.028], sclerotin levels [OR (95% CI): 1.06 (1.0-1.012), p = 0.041] and CTRP3 levels [OR (95%) CI: 1.64 (1.0-2.68), p = 0.047] as significant predictors of OP in diabetic patients. CONCLUSIONS: Sclerostin and CTRP3 levels are involved in OP in postmenopausal diabetic patients.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Densidad Ósea , Proteínas Morfogenéticas Óseas , Diabetes Mellitus Tipo 2 , Osteoporosis Posmenopáusica , Posmenopausia , Humanos , Femenino , Densidad Ósea/fisiología , Proteínas Adaptadoras Transductoras de Señales/sangre , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/sangre , Marcadores Genéticos , Posmenopausia/sangre , Proteínas Morfogenéticas Óseas/sangre , Osteoporosis Posmenopáusica/sangre , Factores de Necrosis Tumoral/sangre , Absorciometría de Fotón , Estudios de Casos y Controles , AncianoRESUMEN
BACKGROUND: Osteoporosis (OP) is a highly prevalent disorder affecting 50 million individuals around the world. It is also a typical skeletal disorder described by low bone mass, which leads to reduced bone strength and an enhanced risk of fractures. Osteoprotegerin As a member of the TNF receptor superfamily, osteoprotegerin is well recognized for its protective effect against excessive bone resorption. Irisin is Irisin is a muscle-secreted hormone that is generated by the cleavage of membrane protein FNDC-5 (fibronectin type III domain-containing protein 5) (FNDC5). Irisin is widely distributed in the human body and is involved in the browning of white adipose tissue, improving insulin resistance, improving cognitive function, and regulating bone metabolism. METHODS: This study was a prospective cross-sectional study involving 90 postmenopausal osteoporosis (PMOP) Iraqi women in Kirkuk City over one year time; from April 2023 to the end of July 2024. Sixty women with osteoporosis are diagnosed by DEXA. And 30 women as a control group. The blood samples were collected from each woman included in this study for the estimation of osteoprotegerin and irisin. Were measured using the ELISA kit. RESULT: This was conducted on sixty postmenopausal osteoporosis women. The age range was (50-65) years and the mean body mass index was (30.05) and thirty women as a control group. The age range was (50-65) years, and the mean body mass index was (27.55). The study found that the mean serum level of osteoprotegerin, increased in postmenopausal osteoporosis women compared to control (P-Value = 0.0007, while the mean serum level of irisin was lower in postmenopausal osteoporosis women compared to control this result was highly significant at a P value of 0.0004. CONCLUSION: This study reveals that there was a positive correlation between serum osteoprotegerin, level with irisin (R=0.175).
Asunto(s)
Fibronectinas , Osteoporosis Posmenopáusica , Osteoprotegerina , Humanos , Femenino , Fibronectinas/sangre , Osteoprotegerina/sangre , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangre , Estudios Transversales , Anciano , Estudios Prospectivos , Densidad ÓseaRESUMEN
BACKGROUND: Acute-phase reactions (APRs) are common among people treated for the first time with zoledronate (ZOL). The current view is that both the APRs caused by ZOL and its efficacy are related to the mevalonic acid pathway. However, the relationship between APRs and ZOL efficacy remains unclear. METHODS: This was a prospective observational cohort study involving postmenopausal women with osteoporosis in Shanghai, China, for 1 year. A total of 108 patients with an average age of 67.4 ± 5.8 years were treated with 5 mg intravenous ZOL for the first time. Data on demographic characteristics, APRs, blood counts, bone turnover markers, including C-telopeptide collagen crosslinks (CTX) and N-terminal propeptide of type 1 collagen (PINP), and bone mineral density (BMD) were collected. RESULTS: (1) The results did not reveal a relationship between APRs and changes in bone turnover markers and BMD but showed that changes in body temperature (T) within 3 days after administration were positively correlated with changes in the BMD of the LS at Month 12 (ß = 0.279 P = 0.034). (2) This effect was mediated mainly by changes in serum CTX (b = 0.046, 95% CI [0.0010-0.0091]). (3) The ROC curve revealed that when T increased by 1.95 °C, the sensitivity and specificity of identifying clinically important changes in LS BMD after 1 year were optimized. CONCLUSIONS: In this study, we tested the hypothesis that people with elevated body T after initial ZOL treatment had greater improvements in BMD and better outcomes. TRIAL REGISTRATION: NCT, NCT03158246. Registered 18/05/2017.
Asunto(s)
Reacción de Fase Aguda , Temperatura Corporal , Conservadores de la Densidad Ósea , Densidad Ósea , Difosfonatos , Imidazoles , Ácido Zoledrónico , Humanos , Ácido Zoledrónico/uso terapéutico , Ácido Zoledrónico/administración & dosificación , Femenino , Anciano , Estudios Prospectivos , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/administración & dosificación , Persona de Mediana Edad , Imidazoles/administración & dosificación , Imidazoles/uso terapéutico , Difosfonatos/uso terapéutico , Difosfonatos/administración & dosificación , Temperatura Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Reacción de Fase Aguda/sangre , Resultado del Tratamiento , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico , Biomarcadores/sangre , Estudios de Cohortes , Valor Predictivo de las PruebasRESUMEN
Objective: This systematic review and meta-analysis aimed to investigate the association between circulating irisin levels and osteoporosis in women, exploring irisin's potential role in the pathophysiology and management of osteoporosis. Method: We searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang, and VIP databases up to January 2023. The inclusion criteria were observational studies reporting on circulating irisin levels in women. The standardized mean difference (SMD) and correlation coefficients with a 95% confidence interval (CI) were used as the main effect measures under a random-effects model. Heterogeneity was evaluated using the Cochrane Q statistic and the I2 statistics. Subgroup analysis and univariate meta-regression analysis were performed to identify the sources of heterogeneity. The quality of the included study was assessed by the Newcastle-Ottawa Score. The quality of evidence was evaluated using the GRADE system. Publication bias was assessed using Begg's and Egger's test, and the trim-and-fill method. Sensitivity analysis was performed to assess the stability of the results. Results: Fifteen studies with a total of 2856 participants met the criteria. The analysis showed significantly lower irisin levels in postmenopausal osteoporotic women compared to non-osteoporotic controls (SMD = -1.66, 95% CI: -2.43 to -0.89, P < 0.0001; I2 = 98%, P < 0.00001) and in postmenopausal individuals with osteoporotic fractures than in non-fractures controls (SMD = -1.25, 95% CI: -2.15 to -0.34, P = 0.007; I2 = 97%, P < 0.00001). Correlation analysis revealed that irisin levels positively correlated with lumbar spine BMD (r = 0.37, 95% CI: 0.18 to 0.54), femoral BMD (r = 0.30, 95% CI: 0.18 to 0.42), and femoral neck BMD (r = 0.31, 95% CI: 0.14 to 0.47) in women. Despite significant heterogeneity, the robustness of the results was supported by using the random effects model and sensitivity analysis. Conclusion: The current evidence suggests that lower irisin levels are significantly associated with osteoporosis and fracture in postmenopausal women, suggesting its utility as a potential biomarker for early detection of osteoporosis and therapeutic target. However, further high-quality prospective research controlling for confounding factors is needed to clarify the relationship between irisin levels and osteoporotic outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023410264.
Asunto(s)
Fibronectinas , Osteoporosis , Femenino , Humanos , Biomarcadores/sangre , Densidad Ósea , Fibronectinas/sangre , Estudios Observacionales como Asunto , Osteoporosis/sangre , Osteoporosis/diagnóstico , Osteoporosis Posmenopáusica/sangreRESUMEN
OBJECTIVE: This study aims to investigate the correlation between changes in bone mineral density (BMD) in postmenopausal women and circulating inflammatory markers. METHODS: This retrospective study focused on postmenopausal women admitted to the orthopedic department of Suzhou Benq Medical Center from June 2022 to December 2023, following predetermined inclusion and exclusion criteria. We retrospectively collected data on initial blood routine test results and bone density measurements for all study subjects upon admission, including parameters such as white blood cell count (WBC), C-reactive protein, interleukin-6 (IL-6), and procalcitonin (PCT). Additionally, the systemic immune-inflammation index (SII) was calculated using neutrophil count, lymphocyte count, and platelet count. Statistical analyses using SPSS and GraphPad software were performed to assess the correlation between bone density and inflammatory markers. RESULTS: Patients were classified into three groups based on BMD results, including 60 individuals in the osteoporosis (OP) group, 127 individuals in the osteopenia group, and 37 individuals in the Normal group, respectively. Principal component analysis analysis suggested that WBC, SII, and postmenopausal OP (PMOP) held significant feature values. Correlation analysis indicated a correlation between WBC (p = 0.021), IL-6 (p = 0.044), SII (p = 0.034), and PMOP. One-way ANOVA analysis revealed significant differences in IL-6 (p = 0.0179), SII (p = 0.0210), and PCT (p = 0.0200) among the three groups. Finally, ROC curve analysis demonstrated that SII (area under the curve = 0.716) has predictive value for PMOP. CONCLUSION: This study identified a certain predictive value for PMOP through the assessment of inflammatory markers in peripheral blood using routine blood tests.
Asunto(s)
Biomarcadores , Densidad Ósea , Posmenopausia , Humanos , Femenino , Posmenopausia/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Biomarcadores/sangre , Anciano , Inflamación/sangre , Inflamación/diagnóstico , Interleucina-6/sangre , Proteína C-Reactiva/análisis , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico , Recuento de Leucocitos , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/diagnóstico , Curva ROCRESUMEN
The activins-follistatins-inhibins (AFI) hormonal system affects bone metabolism. Treatments that alter bone metabolism may also alter the AFI molecules. In this non-randomized, open-label, head-to-head comparative study, circulating levels of the AFI system were evaluated in postmenopausal women with osteoporosis treated for 12 mo with either teriparatide (n = 23) or denosumab (n = 22). Τeriparatide treatment increased activin B (P=.01) and activin AB (P=.004) and the ratios activin A/follistatin (P=.006), activin B/follistatin (P=.007), activin AB/follistatin (P<.001), and activin AB/ follistatin-like 3 (FSTL3) (P=.034). The significant P for trend in group × time interactions of activins B and AB and of the ratio activin AB/FSTL3 remained robust after adjustment for BMI and LS BMD but it was lost for activin B after adjustment for previous antiresorptive treatment. The effect of teriparatide on BMD was attenuated when it was adjusted for baseline activins levels or their 12-mo changes. No changes were observed after denosumab treatment. In conclusion, activins B and AB, as well as the ratios of all activins to follistatin and of activin AB to FSTL3 increased with teriparatide treatment, possibly in a compensatory manner. Future studies are needed to study the potentially important role activins may play in bone biology and any associations with the effect of teriparatide on BMD. Clinical Trials identifier: NCT04206618. ClinicalTrials.gov https://clinicaltrials.gov/search?term=NCT04206618.
Bone and the muscle comprise 2 tissues that are considered to interact with each other, not only through mechanical but also through endocrine signals. Several components of the activinsfollistatinsinhibins (AFI) hormonal system have been shown to be secreted by the muscle and affect the bone possibly contributing to this interplay. We have previously investigated the levels of the AFI molecules in casecontrol studies and reported differences between osteoporotic vs osteopenic vs postmenopausal and premenopausal women with normal BMD. In this 12-mo, non-randomized, open-labeled, head-to-head comparative study, we prospectively compared the effect of antiosteoporotic agents with opposite effect on bone metabolism, that is, teriparatide vs denosumab, on the circulating concentrations of all known molecules of the AFI system in postmenopausal women with osteoporosis. We observed increases of activins after teriparatide treatment, but no effect after denosumab treatment on any of the AFI molecules studied. Since activins are mainly acting in an autocrine way and since activin B and AB have not been extensively studied, further studies in the basic research, preclinical, and clinical research fields are required to expand these observations and fully elucidate physiology and any therapeutic potential.
Asunto(s)
Activinas , Denosumab , Folistatina , Osteoporosis Posmenopáusica , Teriparatido , Humanos , Femenino , Teriparatido/farmacología , Teriparatido/uso terapéutico , Denosumab/uso terapéutico , Denosumab/farmacología , Activinas/sangre , Activinas/metabolismo , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/metabolismo , Folistatina/sangre , Anciano , Persona de Mediana EdadRESUMEN
AIMS: Uric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture. METHODS: An observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray. RESULTS: Higher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures. CONCLUSIONS: In the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures.
Asunto(s)
Densidad Ósea , Posmenopausia , Ácido Úrico , Humanos , Femenino , Ácido Úrico/sangre , Posmenopausia/sangre , Estudios Transversales , Persona de Mediana Edad , Anciano , Fracturas Óseas/sangre , Fracturas Óseas/epidemiología , Vitamina D/sangre , Calcio/sangre , Factores de Riesgo , Hormona Paratiroidea/sangre , Ultrasonografía , Osteoporosis Posmenopáusica/sangre , Fracturas de la Columna Vertebral/sangre , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/diagnóstico por imagenRESUMEN
AIM: To study the association of bone mineral density (BMD) with serum biochemical and immunological markers in postmenopausal women with rheumatoid arthritis (RA). MATERIALS AND METHODS: The study included 173 women with RA (age 61.0 [56.0; 66.0] years). A survey, dual-energy X-ray absorptiometry to measure the BMD of the lumbar spine (LI-LIV), femoral neck (FN) and total hip (TH), routine blood chemistry, measurement of C-reactive protein (CRP), rheumatoid factor, cyclic citrullinated peptide antibodies (CCPA), parathyroid hormone (PTH), vitamin D3, myostatin, follistatin, interleukin-6 (IL-6), IL-6 receptors, insulin-like growth factor 1, adiponectin, leptin, fibroblast growth factor 23, and tumor necrosis factor SF12 were performed. RESULTS: PTH (ß=-0.22, -0.35 and -0.30 for LI-LIV, FN and TH, respectively), CRP (ß=-0.18, 0.23 and -0.22 for LI-LIV, FN and TH, respectively) and leptin (ß=0.35, 0.32 and 0.42 for LI-LIV, FN and TH, respectively) were shown a significant association with BMD in all sites of measurement. It was independent of age, body mass index and postmenopause duration. Associations were also found between adiponectin and BMD of LI-LIV and TH (ß=-0.36 and -0.28, respectively), CCPA and BMD of FN and TH (ß=-0.21, -0.24, respectively) and IL-6 and BMD of FN (ß=0.37). CONCLUSION: The study of biochemical and immunological markers in women with RA demonstrated that CRP, CCPA, PTH, IL-6, adiponectin, and leptin influenced BMD.
Asunto(s)
Artritis Reumatoide , Biomarcadores , Densidad Ósea , Humanos , Femenino , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Artritis Reumatoide/fisiopatología , Densidad Ósea/fisiología , Persona de Mediana Edad , Biomarcadores/sangre , Absorciometría de Fotón/métodos , Anciano , Posmenopausia/sangre , Posmenopausia/inmunología , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Adiponectina/sangre , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/inmunología , Osteoporosis Posmenopáusica/fisiopatología , Osteoporosis Posmenopáusica/etiología , Leptina/sangreRESUMEN
Introduction: Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women. Methods: In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis. Results: The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene. Discussion: Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis.
Asunto(s)
Bacterias , Densidad Ósea , Heces , Microbioma Gastrointestinal , Metabolómica , Posmenopausia , ARN Ribosómico 16S , Humanos , Femenino , Posmenopausia/sangre , Heces/microbiología , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Anciano , Metaboloma , Biomarcadores/sangre , Cromatografía Liquida , Espectrometría de Masas , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/microbiología , Remodelación ÓseaRESUMEN
Osteoporosis (OP) is a common complication of postmenopausal women with rheumatoid arthritis (RA). Herein, the objective of our study was to explore the correlation between serum matrix metalloproteinase 3 (MMP3) and OP among postmenopausal women with RA to foster better diagnosis and treatment. A total of 208 elderly postmenopausal women with RA were included in this study, with 83 patients diagnosed with OP after RA diagnosis and 125 patients without OP. Serum MMP3 levels and bone mineral density (BMD) were measured and compared. The predictive value of serum MMP3 for OP in this population was also analyzed using receiver operating curve (ROC) analysis. Postmenopausal women with RA and OP diagnosis had markedly higher serum MMP3 levels, compared to those without OP. ROC analysis showed that serum MMP3 had predictive value for OP. Additionally, a negative correlation was observed between serum MMP3 levels and BMD. High serum MMP3 levels were also found to be associated with high abnormal bone metabolism. We found that serum MMP3 levels are strongly correlated with OP in postmenopausal women with RA and that elevated levels of serum MMP3 are linked to low BMD and high abnormal bone metabolism. Serum MMP3 may be a useful biomarker for predicting OP in this population, and could potentially aid in the development of targeted prevention and treatment strategies.
Asunto(s)
Artritis Reumatoide , Biomarcadores , Densidad Ósea , Metaloproteinasa 3 de la Matriz , Posmenopausia , Humanos , Femenino , Metaloproteinasa 3 de la Matriz/sangre , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Anciano , Biomarcadores/sangre , Persona de Mediana Edad , Posmenopausia/sangre , Curva ROC , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico , Osteoporosis/sangre , Osteoporosis/etiología , Osteoporosis/diagnósticoRESUMEN
Postmenopausal osteoporosis (PMOP) is a common metabolic inflammatory disease. In conditions of estrogen deficiency, chronic activation of the immune system leads to a hypo-inflammatory phenotype and alterations in its cytokine and immune cell profile, although immune cells play an important role in the pathology of osteoporosis, studies on this have been rare. Therefore, it is important to investigate the role of immune cell-related genes in PMOP. PMOP-related datasets were downloaded from the Gene Expression Omnibus database. Immune cells scores between high bone mineral density (BMD) and low BMD samples were assessed based on the single sample gene set enrichment analysis method. Subsequently, weighted gene co-expression network analysis was performed to identify modules highly associated with immune cells and obtain module genes. Differential analysis between high BMD and low BMD was also performed to obtain differentially expressed genes. Module genes are intersected with differentially expressed genes to obtain candidate genes, and functional enrichment analysis was performed. Machine learning methods were used to filter out the signature genes. The receiver operating characteristic (ROC) curves of the signature genes and the nomogram were plotted to determine whether the signature genes can be used as a molecular marker. Gene set enrichment analysis was also performed to explore the potential mechanism of the signature genes. Finally, RNA expression of signature genes was validated in blood samples from PMOP patients and normal control by real-time quantitative polymerase chain reaction. Our study of PMOP patients identified differences in immune cells (activated dendritic cell, CD56 bright natural killer cell, Central memory CD4 T cell, Effector memory CD4 T cell, Mast cell, Natural killer T cell, T follicular helper cell, Type 1 T-helper cell, and Type 17 T-helper cell) between high and low BMD patients. We obtained a total of 73 candidate genes based on modular genes and differential genes, and obtained 5 signature genes by least absolute shrinkage and selection operator and random forest model screening. ROC, principal component analysis, and t-distributed stochastic neighbor embedding down scaling analysis revealed that the 5 signature genes had good discriminatory ability between high and low BMD samples. A logistic regression model was constructed based on 5 signature genes, and both ROC and column line plots indicated that the model accuracy and applicability were good. Five signature genes were found to be associated with proteasome, mitochondria, and lysosome by gene set enrichment analysis. The real-time quantitative polymerase chain reaction results showed that the expression of the signature genes was significantly different between the 2 groups. HIST1H2AG, PYGM, NCKAP1, POMP, and LYPLA1 might play key roles in PMOP and be served as the biomarkers of PMOP.
Asunto(s)
Biomarcadores , Densidad Ósea , Osteoporosis Posmenopáusica , Humanos , Femenino , Osteoporosis Posmenopáusica/genética , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/inmunología , Densidad Ósea/genética , Biomarcadores/sangre , Persona de Mediana Edad , Perfilación de la Expresión Génica/métodos , Curva ROC , Anciano , Aprendizaje AutomáticoRESUMEN
Osteoporosis is a common condition associated with an increased risk of bone fractures due to fragility. Bone mineral density (BMD) is lower in menopausal women due to estrogen deficiency, age-related decline in osteoblast function, decreased calcium absorption, and reduced synthesis of vitamin D, which lead to osteoporosis. The aim of this study was to determine the correlation between serum vitamin D levels and BMD assessed using radiofrequency echographic multi-spectrometry technology (REMS) in menopausal women. A cross-sectional study was conducted at Prof. Dr. Chairuddin P. Lubis Hospital of Universitas Sumatera Utara, Medan, Indonesia, from May 2023 to August 2023. Consecutive sampling method was employed to sample menopausal women with no history of hysterectomy or oophorectomy (unilateral or bilateral), and no history of hormone replacement therapy or vitamin D supplementation. Interviews and physical examinations were conducted to obtain the characteristics of the subjects (age, duration of menopause, and body mass index). The 25(OH)D level was measured using immunoassay and REMS examination was conducted to assess BMD. The Spearman correlation test was used to assess the correlation between serum vitamin D levels and BMD. A total of 32 menopausal women were included in this study with the average vitamin D level was 18.05±5.81 ng/mL, and the mean BMD level was -2.13±1.23. The data showed a significant positive correlation between serum vitamin D levels and BMD in menopausal women (r=0.710; p=0.020). This study highlights that REMS could be useful as an alternative to dual-energy x-ray absorptiometry (DXA) to assess DMD in postmenopausal women.
Asunto(s)
Densidad Ósea , Menopausia , Vitamina D , Humanos , Femenino , Densidad Ósea/fisiología , Vitamina D/sangre , Vitamina D/análogos & derivados , Estudios Transversales , Persona de Mediana Edad , Indonesia/epidemiología , Menopausia/sangre , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico por imagen , AncianoRESUMEN
BACKGROUND: This study aimed to assess the efficacy and safety of MW031 in Chinese postmenopausal women with osteoporosis. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 448 postmenopausal women with osteoporosis were randomized 3:1 to receive MW031 and placebo for 12 months. The primary efficacy endpoint was the percentage change from baseline in BMD at lumbar spine in month 12. The safety and immunogenicity profiles were also included. RESULTS: Of 448 randomized patients, 421 completed the study (MW031, n = 322; placebo, n = 99).After 12 months of MW031 treatment, BMD increased by 5.80% at lumbar spine,3.65% at total hip, and 2.93% at femoral neck. The model-adjusted difference was 3.86% (P<0.0001), 2.34% (P<0.0001), and 1.05% (p = 0.08) compared with placebo group, respectively. For the bone turnover markers, serum CTX level in MW031 group decreased to the maximum difference in month 1 (-71.71%, 95% CI: -77.83%, -65.60%, P<0.0001) compared with the placebo group. The safety analysis showed no significant differences in the proportion of patients reporting any adverse events between the two groups. CONCLUSION: This study demonstrated that MW031 safely and effectively increased BMD and rapidly decreased the level of bone resorption marker in Chinese postmenopausal women with osteoporosis. TRIAL REGISTRATION: NCT05215977 (ClinicalTrials.gov.).
Asunto(s)
Biosimilares Farmacéuticos , Conservadores de la Densidad Ósea , Densidad Ósea , Denosumab , Osteoporosis Posmenopáusica , Humanos , Femenino , Método Doble Ciego , Persona de Mediana Edad , Denosumab/efectos adversos , Denosumab/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/sangre , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Anciano , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , China , Resultado del Tratamiento , Pueblo Asiatico , Pueblos del Este de AsiaRESUMEN
BACKGROUND AND AIMS: Postmenopausal osteoporosis (PMO) and type 2 diabetes mellitus (T2DM) frequently coexist in postmenopausal women. The study aimed to explore metabolic variations linked to these circumstances and their simultaneous presence through proton nuclear magnetic resonance metabolomics (1H NMR). MATERIALS AND METHODS: Serum samples from 80 postmenopausal women, including 20 PMO individuals, 20 T2DM, 20 T2DM + PMO, and 20 healthy postmenopausal women, were analyzed using 1H NMR spectroscopy. RESULTS: Our study revealed significant metabolic profile differences among the four groups. Notably, the T2DM + PMO group showed elevated levels of alanine, pyruvate, glutamate, lactate, and aspartate, indicating their involvement in lipid metabolism, energy, and amino acids. Importantly, our multivariate statistical analysis identified a metabolite set that accurately distinguished the groups, suggesting its potential as an early diagnostic marker. CONCLUSION: The 1H NMR metabolomics approach uncovered metabolic biomarkers intricately linked to postmenopausal osteoporosis (PMO), type 2 diabetes mellitus (T2DM), and their concurrent presence. Among these biomarkers, alanine emerged as a pivotal player, showing its significant role in the metabolic landscape associated with PMO and T2DM. These findings shed light on the pathophysiological mechanisms underlying these conditions and underscore alanine's potential as a diagnostic biomarker.
Asunto(s)
Biomarcadores , Diabetes Mellitus Tipo 2 , Metabolómica , Osteoporosis Posmenopáusica , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Metabolómica/métodos , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico , Anciano , Espectroscopía de Resonancia Magnética/métodos , MetabolomaRESUMEN
BACKGROUND: Glucocorticoids and sclerostin act as inhibitors of the Wnt signaling pathway, thereby hindering bone formation. Given the pathway's intricate association with mesenchymal stem cells, the hypothesis suggests that heightened sclerostin levels may be intricately linked to an augmentation in marrow adiposity induced by glucocorticoids. This study endeavored to delve into the nuanced relationship between circulating sclerostin and bone marrow adipose tissue in postmenopausal women grappling with glucocorticoid-induced osteoporosis (GIO). METHODS: In this cross-sectional study, 103 patients with autoimmune-associated diseases underwent glucocorticoid treatment, boasting an average age of 61.3 years (standard deviation 7.1 years). The investigation encompassed a thorough assessment, incorporating medical history, anthropometric data, biochemical analysis, and dual-energy X-ray absorptiometry measurements of lumbar and femoral bone mineral density (BMD). Osteoporosis criteria were established at a T-score of -2.5 or lower. Additionally, MR spectroscopy quantified the vertebral marrow fat fraction. RESULTS: BMD at the femoral neck, total hip, and lumbar spine showcased an inverse correlation with marrow fat fraction (r = -0.511 to - 0.647, P < 0.001). Serum sclerostin levels exhibited a positive correlation with BMD at various skeletal sites (r = 0.476 to 0.589, P < 0.001). A noteworthy correlation emerged between circulating sclerostin and marrow fat fraction at the lumbar spine (r = -0.731, 95% CI, -0.810 to -0.627, P < 0.001). Multivariate analysis brought to light that vertebral marrow fat fraction significantly contributed to sclerostin serum concentrations (standardized regression coefficient ß = 0.462, P < 0.001). Even after adjusting for age, body mass index, physical activity, renal function, BMD, and the duration and doses of glucocorticoid treatment, serum sclerostin levels maintained a significant correlation with marrow fat fraction. CONCLUSIONS: Circulating sclerostin levels exhibited a noteworthy association with marrow adiposity in postmenopausal women grappling with GIO.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Adiposidad , Densidad Ósea , Médula Ósea , Glucocorticoides , Posmenopausia , Humanos , Femenino , Persona de Mediana Edad , Glucocorticoides/efectos adversos , Estudios Transversales , Adiposidad/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Anciano , Marcadores Genéticos , Biomarcadores/sangre , Biomarcadores/análisis , Osteoporosis Posmenopáusica/sangre , Absorciometría de FotónRESUMEN
The role of monocytes in postmenopausal osteoporosis is widely recognized; however, the mechanisms underlying monocyte reprogramming remain unknown. In this study, single-cell RNA sequencing (scRNA-seq) was conducted on CD14+ bone marrow monocytes obtained from 3 postmenopausal women with normal BMD and 3 women with postmenopausal osteoporosis (PMOP). Monocle2 was used to classify the monocytes into 7 distinct clusters. The proportion of cluster 1 significantly decreased in PMOP patients, while the proportion of cluster 7 increased. Further analysis via GSEA, transcription factor activity analysis, and sc-metabolic analysis revealed significant differences between clusters 1 and 7. Cluster 7 exhibited upregulated pathways associated with inflammation, immunity, and osteoclast differentiation, whereas cluster 1 demonstrated the opposite results. Monocle2, TSCAN, VECTOR, and scVelo data indicated that cluster 1 represented the initial subset and that cluster 7 represents one of the terminal subsets. BayesPrism and ssGSEA were employed to analyze the bulk transcriptome data obtained from the GEO database. The observed alterations in the proportions of 1 and 7 were validated and found to have diagnostic significance. CD16 serves as the marker gene for cluster 7, thus leading to an increased proportion of CD16+ monocytes in women with PMOP. Flow cytometry was used to assess the consistency of outcomes with those of the bioinformatic analysis. Subsequently, an additional scRNA-seq analysis was conducted on bone marrow mononuclear cells obtained from 3 patients with PMOP and 3 postmenopausal women with normal BMD. The differential proportions of cluster 1 and cluster 7 were once again confirmed, with the pathological effect of cluster 7 may attribute to cell-cell communication. The scRNA-seq findings suggest that an imbalance in monocyte subsets is a characteristic feature of PMOP. These findings elucidate the limitations of utilizing bulk transcriptome data for detecting alterations in monocytes, which may influence novel research inquiries.
Monocytes are a type of white blood cell that plays a role in postmenopausal osteoporosis (PMOP), a condition where bones become weak and brittle after menopause. However, how monocytes change in this condition is not fully understood. In this study, single-cell RNA sequencing was used to analyze bone marrow monocytes from postmenopausal women with normal bone density and those with osteoporosis. Two distinct types of monocytes were identified, which were called clusters 1 and 7. In women with PMOP, there was a decrease in cluster 1 monocytes and an increase in cluster 7 monocytes. This change was validated in external datasets and in peripheral blood. Further analysis showed that cluster 7 monocytes positively correlated with inflammation, immunity, and osteoclast differentiation (a process that leads to bone resorption). Cluster 1 monocytes were found to be the initial subset, while cluster 7 monocytes were one of the terminal subsets. Overall, this study suggests that an imbalance in monocyte subsets is a characteristic feature of postmenopausal osteoporosis. These findings have important implications for understanding the role of monocytes in bone health.
Asunto(s)
Monocitos , Osteoporosis Posmenopáusica , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Humanos , Femenino , Monocitos/metabolismo , Monocitos/patología , Osteoporosis Posmenopáusica/genética , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/sangre , Persona de Mediana Edad , Anciano , Regulación de la Expresión Génica , Transcriptoma , Receptores de Lipopolisacáridos/metabolismoRESUMEN
Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require subcutaneous injections. The purpose of this study was to assess the effects of a novel orally administered PTH tablet on serum markers of bone formation (PINP and osteocalcin), bone resorption (crosslinked C-telopeptide [CTX]), BMD, and safety in postmenopausal women with low BMD or osteoporosis. In this 6-mo, double-blind, placebo-controlled study, 161 patients were randomized to oral PTH tablets containing 0.5, 1.0, 1.5, or 2.5 mg or placebo daily. Biochemical markers were assessed at 1, 2, 3, and 6 mo and BMD of LS, TH, and FN was measured at 6 mo. Biochemical marker changes were dose dependent with minimal or no effect at the 2 lowest doses. At the highest dose (2.5 mg once daily), serum PINP and OC levels increased 30% within 1 mo after oral PTH initiation (P < .0001), remained elevated through 3 mo, and were back to baseline at 6 mo. In contrast, serum CTX levels declined 16% and 21% below baseline at 3 and 6 mo, respectively (both P ≤ .02). At 6 mo, 2.5 mg tablets increased mean BMD vs placebo of the LS by 2.7%, TH by 1.8%, and FN by 2.8% (all P ≤ .01). There were no drug-related serious adverse events. The most common adverse events were headache, nausea, and dizziness. In contrast to subcutaneous PTH, the oral PTH tablet appears to increase BMD rapidly by the dual mechanism of stimulating formation and inhibiting bone resorption. This might be the first effective oral anabolic alternative to subcutaneous administration for the treatment of low BMD or osteoporosis.
Despite the superior benefits of bone-building (anabolic) agents and guidelines supporting their use, these medications are used in a minority of patients for whom they are appropriate, in part because they require daily or monthly injections, which limit patient acceptance. An oral anabolic tablet has potential to address this substantial treatment gap. In this double-blind, placebo controlled, dose-finding randomized study, 161 postmenopausal women with low BMD or osteoporosis were treated with varying doses of the active part of PTH(1-34) or placebo given in daily oral tablets for 6 mo. The highest oral PTH tablet dose (2.5 mg) produced an increase in markers of bone formation while simultaneously decreasing the markers of bone breakdown. Significant gains in BMD of the spine and hip were observed at the end of the 6-mo study and there were no significant safety concerns. The 2.5 mg oral PTH tablet dose was well tolerated when patients were instructed to titrate up to the full dose. We conclude that this PTH tablet might be the first effective orally administered bone building medication and should be studied further in treatment of women with osteoporosis.
Asunto(s)
Densidad Ósea , Humanos , Femenino , Administración Oral , Persona de Mediana Edad , Anciano , Densidad Ósea/efectos de los fármacos , Biomarcadores/sangre , Comprimidos , Posmenopausia/efectos de los fármacos , Posmenopausia/sangre , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/sangre , Método Doble Ciego , Hormona Paratiroidea/sangre , Placebos , Teriparatido/administración & dosificación , Teriparatido/farmacología , Fragmentos de Péptidos/sangreRESUMEN
PURPOSE: Osteoporosis has been a widespread concern for older women, especially postmenopausal women. Thyroid function is crucial for bone metabolism. However, the relationship between thyroid function variation within thyroxine reference range and bone mineral density (BMD) remains ambiguous. The objective of this study was to evaluate the effect of subclinical hypothyroidism or hyperthyroidism on total spinal BMD in postmenopausal women. METHODS: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010, multivariable weighted logistic regression was used to evaluate the relationships between total spine BMD and TSH among postmenopausal women aged ≥50. RESULTS: After accounting for a number of variables, this study discovered that the middle TSH tertile was associated with a decreased probability of osteoporosis. Additionally, the subgroup analysis revealed that postmenopausal women over the age of 65 or people with an overweight BMI had a clearer relationship between total spine BMD and TSH. CONCLUSION: The total spinal BMD had a positive relationship with thyroid stimulating hormone in postmenopausal women, and that appropriate TSH level (1.38-2.32 mIU/L) was accompanied by higher total spinal BMD.
Asunto(s)
Densidad Ósea , Hipertiroidismo , Posmenopausia , Tirotropina , Humanos , Femenino , Densidad Ósea/fisiología , Persona de Mediana Edad , Anciano , Posmenopausia/fisiología , Tirotropina/sangre , Hipertiroidismo/sangre , Hipertiroidismo/fisiopatología , Encuestas Nutricionales , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/sangre , Columna Vertebral , Hipotiroidismo/sangre , Hipotiroidismo/fisiopatología , Hipotiroidismo/epidemiología , Glándula Tiroides/fisiología , Glándula Tiroides/fisiopatología , Pruebas de Función de la TiroidesRESUMEN
Baseline serum PINP value was significantly and independently associated with the increased bone mineral density (≥ 3%) in both total hip and femoral necks by 12 months of romosozumab treatment in patients with treatment-naive postmenopausal osteoporosis. PURPOSE: Some patients fail to obtain a sufficiently increased hip bone mineral density (BMD) by romosozumab (ROMO) treatment. This study aimed to investigate the prognostic factor for increased hip BMD with ROMO in patients with treatment-naive postmenopausal osteoporosis. METHODS: This prospective, observational, and multicenter study included patients (n = 63: mean age, 72.6 years; T-scores of the lumbar spine [LS], - 3.3; total hip [TH], - 2.6; femoral neck [FN], - 3.3; serum type I procollagen N-terminal propeptide [PINP], 68.5 µg/L) treated by ROMO for 12 months. BMD and serum bone turnover markers were evaluated at each time point. A responder analysis was performed to assess the patient percentage, and both univariate and multivariate analyses were performed to investigate the factors associated with clinically significant increased BMD (≥ 3%) in both TH and FN. RESULTS: Percentage changes of BMD from baseline in the LS, TH, and FN areas were 17.5%, 4.9%, and 4.3%, respectively. In LS, 96.8% of patients achieved ≥ 6% increased LS-BMD, although 57.1% could not achieve ≥ 3% increased BMD in either TH or FN. Multiple regression analysis revealed that only the baseline PINP value was significantly and independently associated with ≥ 3% increased BMD in both TH and FN (p = 0.019, 95% confidence interval = 1.006-1.054). The optimal cut-off PINP value was 53.7 µg/L with 54.3% sensitivity and 92.3% specificity (area under the curve = 0.752). CONCLUSIONS: In a real-world setting, baseline PINP value was associated with the increased BMD of TH and FN by ROMO treatment in treatment-naive patients.
Asunto(s)
Conservadores de la Densidad Ósea , Densidad Ósea , Osteoporosis Posmenopáusica , Anciano , Femenino , Humanos , Biomarcadores/sangre , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/efectos de los fármacos , Osteoporosis , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico por imagen , Osteoporosis Posmenopáusica/tratamiento farmacológico , Procolágeno/sangre , Estudios Prospectivos , Teriparatido , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/efectos de los fármacos , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/efectos de los fármacosRESUMEN
Background: Osteoporosis is one of the most common systemic metabolic bone diseases, especially in postmenopausal women. Circular RNA (circRNA) has been implicated in various human diseases. However, the potential role of circRNAs in postmenopausal osteoporosis (PMOP) remains largely unknown. The study aims to identify potential biomarkers and further understand the mechanism of PMOP by constructing a circRNA-associated ceRNA network. Methods: The PMOP-related datasets GSE161361, GSE64433, and GSE56116 were downloaded from the Gene Expression Omnibus (GEO) database and were used to obtain differentially expressed genes (DEGs). Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to determine possible relevant functions of differentially expressed messenger RNAs (mRNAs). The TRRUST database was used to predict differential transcription factor (TF)-mRNA regulatory pairs. Afterwards, combined CircBank and miRTarBase, circRNA-miRNA as well as miRNA-TF pairs were constructed. Then, a circRNA-miRNA-TF-mRNA network was established. Next, the correlation of mRNAs, TFs, and PMOP was verified by the Comparative Toxicogenomics Database. And expression levels of key genes, including circRNAs, miRNAs, TFs, and mRNAs in the ceRNA network were further validated by quantitative real-time PCR (qRT-PCR). Furthermore, to screen out signaling pathways related to key mRNAs of the ceRNA network, Gene Set Enrichment Analysis (GSEA) was performed. Results: A total of 1201 DE mRNAs, 44 DE miRNAs, and 1613 DE circRNAs associated with PMOP were obtained. GO function annotation showed DE mRNAs were mainly related to inflammatory responses. KEGG analysis revealed DE mRNAs were mainly enriched in osteoclast differentiation, rheumatoid arthritis, hematopoietic cell lineage, and cytokine-cytokine receptor interaction pathways. We first identified 26 TFs and their target mRNAs. Combining DE miRNAs, miRNA-TF/mRNA pairs were obtained. Combining DE circRNAs, we constructed the ceRNA network contained 6 circRNAs, 4 miRNAs, 4 TFs, and 12 mRNAs. The expression levels of most genes detected by qRT-PCR were generally consistent with the microarray results. Combined with the qRT-PCR validation results, we eventually identified the ceRNA network that contained 4 circRNAs, 3 miRNAs, 3 TFs, and 9 mRNAs. The GSEA revealed that 9 mRNAs participate in many important signaling pathways, such as "olfactory transduction", "T cell receptor signaling pathway", and "neuroactive ligand-receptor interaction". These pathways have been reported to the occurrence and development of PMOP. To sum up, key mRNAs in the ceRNA network may participate in the development of osteoporosis by regulating related signal pathways. Conclusions: A circRNA-associated ceRNA network containing TFs was established for PMOP. The study may help further explore the molecular mechanisms and may serve as potential biomarkers or therapeutic targets for PMOP.