Guoqi Cai

Background: Osteoporosis (OP) is a common metabolic bone disease whose onset and progression are influenced by sleep patterns. However, previous related studies have mostly relied on self-reported sleep data and have often been confined to a single dimension such as sleep duration. Therefore, this study aimed to evaluate the associations between multidimensional, objective sleep characteristics and OP. Methods: This study was based on the UK Biobank and included 72,211 participants. Five objective sleep metrics were derived from 7 consecutive days of wrist accelerometer data: sleep duration, sleep efficiency, sleep regularity index, sleep midpoint, and relative amplitude. Incident OP events were identified through linkage with electronic medical records. Multivariable Cox proportional hazards models were used to examine the associations between objective sleep metrics and OP. Restricted cubic splines (RCS) were applied to test potential nonlinear relationships. Interaction analyses and sex-stratified subgroup analyses were also conducted based on the above results. Results: Average sleep duration (HR = 0.91, 95% CI: 0.87–0.95; P < 0.001), sleep efficiency (HR = 0.92, 95% CI: 0.88–0.97; P = 0.001), and relative amplitude (HR = 0.80, 95% CI: 0.76–0.85; P < 0.001) were all associated with a reduced risk of OP. RCS analyses showed no significant nonlinear effects (all P _nonlinear > 0.05). Interaction analysis suggested a significant negative interaction between relative amplitude and sleep duration (HR 0.96, 95% CI 0.93–0.99; P = 0.012). In sex-stratified subgroup analyses, the pattern of associations in women was consistent with the main analysis, whereas in men only sleep duration and relative amplitude were significantly associated with lower OP risk (all P < 0.05). Conclusions: Longer objective sleep duration, higher sleep efficiency, and stronger relative amplitude were independently associated with a lower risk of OP. The association between sleep duration and OP also varied by relative amplitude. These findings suggest that objective sleep characteristics and behavioral rest-activity rhythmicity may be relevant to OP risk, although further mechanistic and interventional studies are needed to clarify causality.

Objective: To explore the association between periarticular subchondral bone mineral density (sBMD) and the presence and progression of osteoarthritis (OA) knee pain. Methods: Participants were recruited from the Osteoarthritis Initiative (OAI). Tibial sBMD at medial and lateral compartments was measured by dual-energy x-ray absorptiometry at 30 or 36 months (baseline) and reassessed at 48 months. Knee pain was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale (range 0-20, with a higher score indicating greater pain) through month 108. Baseline knee pain was categorized as low/no or high (pain score < 5 vs ≥ 5). Pain progression was defined as an increase in WOMAC pain score of ≥ 2 in at least 3 of the 6 follow-up visits. Logistic regression with generalized estimating equations was used to assess associations between sBMD (per SD increase) and knee pain, accounting for within-participant correlation between knees. Results: Of 594 participants (mean age 64.1 years; 50.5% male; 1137 knees), 31.6% of knees exhibited higher pain at baseline, and 37.4% demonstrated pain progression during follow-up. Higher medial sBMD and medial-to-lateral sBMD ratio were associated with the progression of knee pain (medial sBMD: odds ratio [OR] 1.50; 95% CI 1.25-1.81; P < 0.001; medial-to-lateral ratio: OR 1.29; 95% CI 1.11-1.49; P = 0.001). Medial-to-lateral sBMD ratio was also associated with the presence of knee pain (OR 1.21; 95% CI 1.05-1.40; P = 0.01). Conclusion: Higher medial-to-lateral sBMD ratio was associated with both the presence and progression of knee pain, suggesting that relative subchondral bone distribution may better capture biomechanical loading imbalance related to symptomatic OA than absolute sBMD alone.

Background: Obesity is a key contributor to type 2 diabetes, and weight loss is a central component of diabetes management. Although clinical guidelines recommend that healthcare providers offer weight management advice, its real‐world impact remains unclear. Objective: This study assessed the associations of doctor‐advised and self‐initiated weight management with weight loss among individuals with type 2 diabetes who are overweight or obese. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES 2011–2018). People with diabetes and overweight or obesity (body mass index ≥ 25 kg/m ² ) were categorized into four groups according to doctor‐advised weight loss and weight management status. Outcomes included one‐year weight change, assessed both continuously (percentage change) and categorically (≥ 5% and ≥ 10% weight loss). Linear regression was used for continuous outcomes and Poisson regression with robust standard errors for categorical weight loss. Results: Among 1715 individuals (61.1 ± 12.4 years, 49.1% female), 1020 received doctor‐advised weight loss, and 89.6% initiated weight management. However, individuals who received advice achieved less weight loss than those not advised, particularly among those who did not engage in weight management ( β : 5.07, 95% CI 3.07 to 7.07, p < 0.001). Individuals who received advice were also substantially less likely to achieve ≥ 5% (RR 0.15, 95% CI 0.06 to 0.39, p < 0.001) or ≥ 10% weight loss (RR 0.20, 95% CI 0.10 to 0.41, p < 0.001). Conclusions: Only three out of five participants with diabetes and overweight or obesity were advised by healthcare providers to lose weight. While weight loss advice spurred individuals to engage in weight management, those who received weight loss advice encounter greater challenges in reaching weight loss targets.

Objectives To explore the association between serum vitamin D levels and the risk of knee and hip osteoarthritis (KOA and HOA). Methods This study included 295,557 participants (mean 56 years, 53% female) from the UK Biobank who had data on serum vitamin D levels and did not have KOA or HOA at baseline. The associations between serum vitamin D levels and the incidences of KOA and HOA were evaluated using Cox regression models. Mediating effects of serum biomarkers of inflammation (IL-1a, IL-1b, IL-6, and TNF) and cartilage metabolism (COMP, CRTAC1, and COL9A1) were explored. Results During a median follow-up of 13.1 years, 12,266 (4.2%) and 8931 (3.0%) participants developed KOA and HOA, respectively. Serum vitamin D levels were positively associated with osteoarthritis risk (KOA—hazard ratio [HR] = 1.14, 95% confidence interval [CI] 1.12–1.17; HOA—HR = 1.09, 95% CI 1.06–1.12). Compared to participants with severe vitamin D deficiency (< 25 nmol/L), those with sufficient vitamin D levels (≥ 75 nmol/L) had a 55% and 30% higher risk of developing KOA and HOA, respectively. Cartilage metabolism markers, but not inflammation markers, mediated 5.6%–12.6% of the associations between serum vitamin D levels and KOA risk. Conclusion High serum vitamin D levels are associated with an increased risk of OA in middle-aged and older adults. While serum vitamin D has recognized benefits for bone and cardiovascular health, these findings highlight a potential association with osteoarthritis risk without suggesting a causal effect. Key Points • High vitamin D levels increase osteoarthritis risk. • Cartilage metabolism partially mediates this association. • Inflammatory markers show no mediating effect.

Linear regression models for repeated measures have been widely used in clinical trials to compare treatment effects on continuous outcome measures. These models often include baseline covariates to improve precision and adjust for potential confounding. However, a common misapplication arises when baseline variables are included in the model without incorporating interaction terms between each covariate and time. This modeling strategy implicitly assumes that the covariates have constant effects over time but, crucially, it fails to adjust the treatment-by-time interaction, which is typically the primary parameter of interest. As a result, the inclusion of baseline covariates in this way does not truly adjust the estimated treatment effect over time. To properly account for baseline differences in repeated-measures models, interaction terms between each covariate and time should be taken into account and carefully treated. This approach ensures that baseline covariates can differentially influence the outcome at different time points, and thus appropriately adjust the estimated treatment effect. To demonstrate the practical implications of this issue, we analyzed real data from 2 randomized controlled trials (RCTs) and conducted simulation studies. The results showed that including covariates without time interaction terms led to no change in the estimated treatment effect, whereas proper inclusion of interaction terms yielded different conclusions.

To evaluate the independent and combined effects of metabolic abnormalities and obesity on the risk of knee and hand osteoarthritis (KOA and HOA). Particip

This study aimed to investigate the role of Piezo1 in the immune-inflammatory response during the pathogenesis of ankylosing spondylitis (AS) and its underlying mechanisms. RT-qPCR was used to evaluate the expression levels of Piezo1 and autophagy-related genes in the peripheral blood of AS patients. Correlation analyses were conducted to evaluate associations between Piezo1 expression and clinical characteristics of AS patients. Immunohistochemistry (IHC) and Western blotting were performed to determine the expression of Piezo1 and autophagy-related proteins in the synovium of AS patients. In vitro, the effects of Piezo1 and autophagy on primary monocyte-derived macrophages and fibroblast-like synoviocytes (FLS) from AS patients were investigated using Yoda1 and 3-MA interventions. Modulation of the immune-inflammatory response via the Piezo1-autophagy axis was examined through RT-qPCR, Western blotting, and ELISA. Finally, the role of Piezo1 in immune regulation was further assessed in proteoglycan-induced arthritis (PGIA) model using GsMTx4, a Piezo1 inhibitor. Piezo1 expression was markedly elevated in AS patients compared to healthy controls and showed a positive correlation with disease activity, duration, and autophagy levels. Mechanistically, increased Piezo1 expression induced M1 polarization of monocyte-macrophages, leading to increased autophagy and the upregulation of inflammatory factors. Additionally, Piezo1 enhanced autophagy and IL-6 activation in FLS. In the PGIA model, GsMTx4 inhibited autophagy hyperactivation, significantly reduced the immune-inflammatory response, and exerted a protective effect on spinal bone tissue. Immunofluorescence further confirmed that these effects might be associated with reduced autophagy and inflammatory cytokine expression in macrophages and FLS. These findings highlight the role of Piezo1 in AS pathogenesis, suggesting that Piezo1 may contribute to the immune-inflammatory response in AS through autophagy regulation.