Frailty phenotype as mediator between systemic inflammation and osteoporosis and fracture risks: A prospective study

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: 15(3), P. 897 - 906

Published: March 11, 2024

Abstract Background Systemic inflammation and frailty have been implicated in osteoporosis (OP) fracture risks; however, existing evidence remains limited inconclusive. This study aimed to assess the associations of systemic phenotype with incident OP evaluate mediating role phenotype. Methods The present analysed data from UK Biobank, a comprehensive representative dataset encompassing over 500 000 individuals general population. Baseline peripheral blood cell counts were employed calculate markers, including neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte (PLR) immune‐inflammation index (SII). Frailty was assessed using five criteria, defined as frail (≥3 items met), pre‐frail (1–2 met) non‐frail (0 met). events confirmed through participants' health‐related records. Multivariable linear Cox regression models utilized, along mediation analysis. Results Increased associated increased risks fracture. corresponding hazard ratios 95% confidence intervals (CIs) for risk per standard deviation increase log‐transformed NLR, PLR SII 1.113 (1.093–1.132), 1.098 (1.079–1.118) 1.092 (1.073–1.111), risk, they 1.066 (1.051–1.082), 1.059 (1.044–1.075) 1.073 (1.058–1.089), respectively. Compared individuals, ones showed an elevated by 21.2% (95% CI: 16.5–26.2%) 111.0% 98.1–124.8%), respectively, 6.1% 2.8–9.5%) 38.2% 30.7–46.2%), level demonstrated positive association frailty, β CI) 0.034 (0.031–0.037), 0.026 (0.023–0.029) 0.008 (0.005–0.011) response increment SII, NLR PLR, mediated between OP/fracture risk. Subgroup sensitivity analyses robustness these findings. Conclusions are independently linked partially mediates osteoporotic traits. These results highlight significance interventions targeting prevention management.

Language: Английский

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Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5720 - 5739

Published: June 2, 2024

Abstract Alzheimer's disease (AD) is a neurodegenerative that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between brain and bone, but interaction bone AD remains unclear. In this review, we summarize human of association provide an overview their interactions underlying mechanisms AD. We review effects on from aspects pathogenic proteins, risk genes, neurohormones, neuropeptides, neurotransmitters, brain‐derived extracellular vesicles (EVs), autonomic nervous system. Correspondingly, elucidate involvement pathogenesis AD, including bone‐derived hormones, marrow‐derived cells, EVs, inflammation. On basis brain, propose potential strategies for management with hope offering novel perspectives its prevention treatment. Highlights The along consequent changes may involve disturbing homeostasis. Degenerative disorders influence progression through series pathophysiological mechanisms. Therefore, relevant intervention be beneficial comprehensive

Language: Английский

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Relationship of Apolipoprotein B to Aortic Aneurysm: Frailty Index as a Partial Mediator – a Mendelian Randomization Study

Kardiologiia, Journal Year: 2025, Volume and Issue: 65(2), P. 57 - 63

Published: Feb. 28, 2025

Aim Aortic aneurysm is characterized by localized expansion and damage to the vessel wall. While apolipoprotein B (ApoB) has been linked atherosclerosis, its causal relationship with aortic remains unclear. This study used a Mendelian randomization (MR) approach explore relationships between ApoB, aneurysm, potential mediators. Material methods Single nucleotide polymorphism (SNP) data related A1 (ApoA1), triglycerides, frailty index, were obtained from large-scale genome-wide association studies. MR analysis was conducted evaluate relationships, using inverse variance weighting (IVW) as primary statistical method. Additionally, we assessed whether index mediates ApoB aneurysm. Results Univariate revealed that significantly associated (IVW odds ratio (OR) = 1.443, 95 % confidence interval (CI) 1.273–1.637, p < 0.001). Multivariable (MVMR) analysis, adjusted for ApoA1 confirmed these results. In mediation found partially mediate effect of on (mediation contribution: 20.1 %–23.1 %). The ORs respect 1.325 (95 CI 1.168–1.505) 4.188 1.859–9.435), respectively. Conclusion acting partial mediator in this pathway.

Language: Английский

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Laboratory-based Biomarkers for Risk Prediction, Auxiliary Diagnosis and Post-operative Follow-up of Osteoporotic Fractures

Current Osteoporosis Reports, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 8, 2025

Osteoporosis (OP) is characterized by degraded bone microstructure, loss of mass and increased risk fragility fractures. Currently, T-score determined dual-energy X-ray absorptiometry (DEXA) measurements has been regarded as the gold standard for diagnosis osteoporosis. However, multiple factors have indicated that insufficient to identify individuals with osteoporosis at a potentially high fracture, or accurately detect those who require treatment, continuously monitor re-fracture clinical outcomes after treatment. This review covers publications in range ten years comprehensively summarizes studies laboratory-based biomarkers osteoporotic fractures (OF), aiming provide physicians surgeons an update research identification, verification application these tools, useful information design future studies. It was found formation markers (such PINP, BGP, ECM1 SOST), resorption β-CTX, TRAcP5b, osteocalcin, RANKL, RANKL/OPG ratio, t-PINP/β-CTX), hormonal IGF- 1, PTH, leptin, adiponectin AMH), indicators inflammation oxidative stress (SII, IL- 6, LTL, FlOP_360, FlOP_400, GGT), microRNAs miR- 21, 320a- 3p, 491 - 5p, 485 19b- 1- 203a, 31 502 4739, 497, 19b, 107), other (SAF-AGEs glycine), adipocytokines (irisin Omentin- 1), senescence (RDW), lncRNAs (MIAT) may be practice. Further validation better understanding underlying molecular mechanisms help development prediction OF, differential among OP, OF healthy individuals, well post-operative monitoring treatment outcomes.

Language: Английский

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Predictive Value of Inflammation Markers for Frailty in Older Patients with CVD

Clinical Interventions in Aging, Journal Year: 2025, Volume and Issue: Volume 20, P. 435 - 447

Published: April 1, 2025

Chronic inflammation plays a pivotal role in the development of frailty patients with cardiovascular diseases (CVD). Systemic inflammatory response index (SIRI) has been shown to reflect overall status. This study aimed investigate relationship between SIRI and older CVD, develop nomogram for predicting risk this population. A total 234 CVD were included. Inflammation markers derived from routine blood tests, status was assessed using FRAIL scale. Clinical laboratory characteristics compared or without frailty. Multivariate logistic regression employed identify significant variables inclusion nomogram. The performance nomogram, including its discrimination calibration, rigorously evaluated. 98 cases assigned group 136 non-frailty group. Patients generally younger, more likely have normal kidney function, better pressure control. Frail exhibited higher degree systemic non-frail (P < 0.05). Age, LDL-C identified as three independent factors potential patients. Therefore, we constructed clinical model based on age, SIRI. had considerable discriminative calibrating abilities. In summary, our demonstrated association elevated levels markers, particularly SIRI, an increased Furthermore, by integrating established predict CVD.

Language: Английский

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Deciphering the Threshold and Segmented Nonlinear Association Between Systemic Inflammation Response Index and Spinal Bone Density: Insights From a Large-Scale Population Study

Global Spine Journal, Journal Year: 2025, Volume and Issue: unknown

Published: May 21, 2025

Study Design Cross-sectional study. Objective To examine the association between SIRI and spinal BMD assess influence of age, hypertension, diabetes. Methods We analyzed data from 13,950 participants aged ≥20 years. was calculated using neutrophil, monocyte, lymphocyte counts, measured by DXA. Linear regression, generalized additive models, segmented regression were used, with subgroup analyses based on Results A threshold effect observed at = 0.68. Below this threshold, negatively correlated (β −0.0412, P 0.0494), while above it, a positive correlation found 0.0079, < 0.0001). Subgroup showed stronger associations in older adults (≥65 years, β 0.0136, 0.0001), those hypertension 0.0089, 0.0004) diabetes 0.0187, 0.001). Conclusion nonlinear relationship exists BMD, as significant modifiers. may serve biomarker for osteoporosis risk.

Language: Английский

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Exploring the Association Between Immune Cell Phenotypes and Osteoporosis Mediated by Inflammatory Cytokines: Insights from GWAS and Single-Cell Transcriptomics

ImmunoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 14, P. 227 - 246

Published: March 1, 2025

Patients with osteoporosis experience increased fracture risk and decreased quality of life, which pose significant health burdens financial challenges. Despite established links between immune cell phenotypes inflammatory cytokines osteoporosis, the exact mechanism involved remains unclear, further understanding is needed for effective prevention treatment. Here, we performed a two-sample Mendelian randomization (MR) study to estimate causal effects 731 types, 91 41 factors (which may have some overlap), 5 types osteoporosis. In subsequent mediation MR analysis, assessed whether these mediate relationship Additionally, colo- calization analysis was using Bayesian colocalization. Single-cell transcriptomic datasets from patients available in Gene Expression Omnibus (GEO) database. Subsequently, single-cell sequencing performed, including dimensionality reduction, clustering, pathway enrichment, investigate underlying mechanisms. Finally, confirm critical role IgD⁺CD24⁺ B cells IL-17C vivo dexamethasone-induced model. Micro-CT used assess effectiveness model establishment. Flow cytometry determine proportion within lymphocytes blood. ELISA Western blotting were measure levels serum bone tissue. Immunohistochemistry conducted evaluate expression This found that 32 38 significantly associated Mediation indicated IgD+ CD24+ exacerbated by influencing interleukin-17C (IL-17C). The mediated effect 0.07837, accounting 15.5% total effect. transcriptome supported play key musculoskeletal-related pathways patients. demonstrated involvement disease Inflammatory crucial pathogenesis immunity-related particular, %lymphocyte increase modulating interleukin-17C. Our results provide evidence support link immunity offer new therapeutic strategies targeting immune-mediated

Language: Английский

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Osteosarcopenia, osteoarthritis and frailty: a two-sample Mendelian randomization study

Aging Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: 37(1)

Published: April 21, 2025

Abstract Background Musculoskeletal disease, which has a complicated relationship with frailty, is common clinical problem among elderly individuals. Aims This study evaluated the potential causal relationships between osteosarcopenia, osteoarthritis and frailty by Mendelian Randomization (MR) analysis. Methods employed two-sample MR approach to investigate frailty. Published summary statistics were used obtain instrumental variables at genome-wide significance level. Results Among age groups osteoporosis, high total bone mineral density (TBMD) (45—60, OR = 0.966, 95% CI 0.940–0.993, P 0.013) TBMD (over 60, 0.974, 0.954–0.994, 0.011) reduced risk of Similarly, forearm BMD (FA-BMD), ultradistal (UFA-BMD), Heel-BMD different sites also (OR 0.936–0.996, 0.028; 0.975, 0.953–0.997, 0.029; 0.981, 0.967–0.995, 0.008). characteristics related sarcopenia, grip strength in left hand, right appendicular lean mass, walking pace all protective factors for 0.788, 0.721–0.862, < 0.001; 0.800, 0.737–0.869, 0.955, 0.937–0.974, 0.000; 0.480, 0.388–0.593, 0.001), low those over 60 years significantly positively correlated 1.168, 1.059–1.289, 0.002). The results revealed specific joint including KOA 1.086, 1.017–1.160, 0.014), HOA 1.028, 1.007–1.049, 0.009), KOA/HOA 1.082, 1.053–1.113, 0.000), increasing Conclusion Osteosarcopenia, exhibit significant effects, rendering them Therefore, practice, patients osteosarcopenia should be required undergo relevant interventions reduce

Language: Английский

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Osteoporosis in older patients with idiopathic normal pressure hydrocephalus

Osteoporosis International, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Language: Английский

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Systemic Immune‐Inflammation‐Based Biomarker and Fragility Fractures in People Living With HIV: A 10‐Year Follow‐Up Cohort Study in China

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(11)

Published: Nov. 1, 2024

ABSTRACT Fragility fractures are a significant concern among people living with HIV(PLWH) due to the combined effects of chronic inflammation, immune dysregulation, and antiretroviral therapy. Traditional biomarkers have limited predictive value for fragility in this population. This study aims evaluate systemic inflammation‐based scores as novel predicting PLWH China. We conducted cohort orthopedic department Beijing Ditan Hospital from January 2011 September 2023. monitored collected data on demographics, clinical characteristics, laboratory parameters. Multivariate Cox logistic regression models were used assess neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte (PLR), monocyte‐to‐lymphocyte (MLR), immune‐inflammation index (SII), inflammation response (SIRI) fractures. Restricted cubic splines (RCS) employed explore potential nonlinear relationships, subgroup analyses examine stability these associations. During median follow‐up 5.5 years, our included 1148 patients, 204 patients (17.8%) experienced After adjusting all covariates, SII SIRI identified independent risk factors PLWH, whereas NLR, PLR, MLR not. Patients higher levels had significantly increased compared those lower (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 1.83, 1.16–2.88, 0.009). RCS analysis indicated stable linear relationship between Furthermore, KM curves demonstrated that likelihood experiencing Our research shows promising PLWH. Clinicians should consider incorporating into practice improve fracture stratification guide preventive strategies vulnerable

Language: Английский

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