Objectives. Thyroid hormone is acknowledged as a pivotal factor in skeletal development and adult bone maintenance. However, available data about the relationship between sensitivity to thyroid hormone and bone mineral density (BMD) remain limited and conflicting. The purpose of the study was to explore the complex relationship between sensitivity to thyroid hormone indices and BMD using cross-sectional analysis. Methods. An overall sample of 3,107 males from the National Health and Nutrition Examination Survey (NHANES) was studied in the study. The thyroid hormone sensitivity indices included free triiodothyronine/tree thyroxine (FT3/FT4), thyroid-stimulating hormone index (TSHI), thyrotroph thyroxine resistance index (TT4RI), and thyroid feedback quantile-based index (TFQI). Given the complex study design and sample weights, the correlation between sensitivity to thyroid hormone indices and BMD was evaluated through multivariate linear regression models, and extra subgroup analyses were performed to examine the robustness of the results. Results. Among the 3,107 participants, we demonstrated that FT3/FT4 was negatively correlated with lumbar BMD (β = −0.0.35, 95% CI: −0.084–0.013, P < 0.05 ). In the terms of central sensitivity to thyroid hormone, TFQI showed a significant negative relationship with the BMD of the lumbar (β = −0.018, 95% CI: −0.033 to −0.003, P < 0.05 ), total femur (β = −0.020, 95% CI: −0.035 to −0.006, P < 0.01 ), and femur neck (β = −0.018, 95% CI: −0.031 to −0.005, P < 0.01 ). In the subgroup analyses stratified by body mass index (BMI), the significant negative correlation between TFQI and lumbar BMD remained in the male participants with BMI between 18.5 and 24.9 kg/m2. Conclusions. Decreased indices of sensitivity to thyroid hormones are strongly associated with increased lumbar BMD, suggesting that the dysfunction of peripheral and central response to thyroid hormone might contribute to bone loss. In addition, FT3/FT4 and TFQI were considered to be the preferable indicators to guide the prevention and clinical treatment of osteoporosis.
Objectives Thyroid hormones play an instrumental role in chondrogenic differentiation and matrix maturation. However, studies investigating the relationship between thyroid function and the risk of osteoarthritis (OA) remain scarce. This study was designed to investigate the correlation between thyroid status and OA from a novel perspective of sensitivity to thyroid hormones. Methods The study included 8478 people from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. The sensitivity to thyroid hormone indices included Thyrotroph Thyroxine Resistance Index (TT4RI), Thyroid-stimulating hormone (TSHI), Thyroid Feedback Quantile-based Index (TFQI), and Free Triiodothyronine /Free thyroxine (FT3/FT4), which were calculated based on serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH). Considering the complex survey design and sample weights, we employed multivariate linear regression models and stratified analysis to evaluate the correlation between sensitivity to thyroid hormone indices and OA. Results Study results indicated that participants with OA had elevated TT4RI, TSHI, and TFQI levels, and lower FT3/FT4 levels compared to those with non-arthritis. After adjusting for other covariates, FT3/FT4 was negatively associated with the risk of OA (OR = 1.162, 95%CI 1.048–1.478, P = 0.021); (OR = 1.261, 95%CI 1.078–1.623, P = 0.042). In subgroup analyses stratified by gender and BMI, participants with OA had higher TFQI levels compared to those without OA in both genders. (OR = 1.491, 95%CI 1.070–2.077, P = 0.018); (OR = 2.548, 95%CI 1.929–3.365, P < 0.001). The higher TFQI levels were consistently associated with the increased prevalence of OA in the BMI (< 18.5 kg/m2) group after adjusting for different covariates, but not in other BMI groups. In, addition, TFQI performed better than FT3/FT4, TSHI, and TT4RI on ROC analyses for OA prediction. Conclusions The levels of FT3/FT4, TSHI, TT4RI, and TFQI are strongly associated with the prevalence of OA, which illustrates the complex correlation between the thyroid system and chondrogenic differentiation. TFQI may be used as a helpful indicator to predict OA and provide novel ideas for the evaluation and treatment of OA.
BackgroundRecent studies have reported that the gut microbiota is essential for preventing and delaying the progression of osteoporosis. Nonetheless, the causal relationship between the gut microbiota and the risk of osteoporosis has not been fully revealed.MethodsA two-sample Mendelian randomization (MR) analysis based on a large-scale genome-wide association study (GWAS) was conducted to investigate the causal relationship between the gut microbiota and bone mineral density (BMD). Instrumental variables for 211 gut microbiota taxa were obtained from the available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. The summary-level data for BMD were from the Genetic Factors for Osteoporosis (GEFOS) Consortium, which involved a total of 32,735 individuals of European ancestry. The inverse variance-weighted (IVW) method was performed as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses by using multiple methods. Finally, a reverse MR analysis was applied to evaluate reverse causality.ResultsAccording to the IVW method, we found that nine, six, and eight genetically predicted gut microbiota were associated with lumbar spine (LS) BMD, forearm (FA) BMD, and femoral neck (FN) BMD, respectively. Among them, the higher genetically predicted Genus Prevotella9 level was correlated with increased LS-BMD [β = 0.125, 95% confidence interval (CI): 0.050–0.200, P = 0.001] and FA-BMD (β = 0.129, 95% CI: 0.007–0.251, P = 0.039). The higher level of genetically predicted Family Prevotellaceae was associated with increased FA-BMD (β = 0.154, 95% CI: 0.020–0.288, P = 0.025) and FN-BMD (β = 0.080, 95% CI: 0.015–0.145, P = 0.016). Consistent directional effects for all analyses were observed in both the MR-Egger and weighted median methods. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on BMD (P > 0.05). In reverse MR analysis, there was no evidence of reverse causality between LS-BMD, FA-BMD, and FN-BMD and gut microbiota (P > 0.05).ConclusionGenetic evidence suggested a causal relationship between the gut microbiota and BMD and identified specific bacterial taxa that regulate bone mass variation. Further exploration of the potential microbiota-related mechanisms of bone metabolism might provide new approaches for the prevention and treatment of osteoporosis.
Background Osteoarthritis (OA) and sarcopenia are common musculoskeletal disorders in the aged population, and a growing body of evidence indicated that they mutually influence one another. Nevertheless, there was still substantial controversy and uncertainty about the causal relationship between sarcopenia and OA. We explored the complex association between sarcopenia-related traits and OA using cross-sectional analysis and Mendelian randomization (MR). Methods The cross-sectional study used the data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Weighted multivariable-adjusted logistic regression and subgroup analyses were used to evaluate the correlation between sarcopenia, grip, appendicular lean mass (ALM) and the risk of OA. Then, we further performed MR analysis to examine the causal effect of sarcopenia-related traits (grip strength, ALM) on OA. Instrumental variables for grip strength and ALM were from the UK Biobank, and the summary-level data for OA was derived from the Genetics of Osteoarthritis (GO) Consortium GWAS (n = 826,690). Results In this cross-sectional analysis, we observed that sarcopenia, grip were significantly linked with the risk of OA (OR 1.607, 95% CI 1.233–2.094, P < 0.001), (OR 0.972, 95% CI 0.964–0.979, P < 0.001). According to subgroup analyses stratified by gender, body mass index (BMI), and age, the significant positive relationship between sarcopenia and OA remained in males, females, the age (46–59 years) group, and the BMI (18.5–24.9 kg/m2) group (P < 0.05). Furthermore, MR analysis and sensitivity analyses showed causal associations between right grip, left grip and KOA (OR 0.668; 95% CI 0.509 to 0.877; P = 0.004), (OR 0.786; 95% CI 0.608 to 0.915; P = 0.042). Consistent directional effects for all analyses were observed in both the MR-Egger and weighted median methods. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy or outliers for the causal effect of grip strength on KOA (P > 0.05). Conclusions Our research provided evidence that sarcopenia is correlated with an increased risk of OA, and there was a protective impact of genetically predicted grip strength on OA. These findings needed to be verified in further prospective cohort studies with a large sample size.
Purpose It is known that muscle strength and muscle mass play a crucial role in maintaining bone mineral density (BMD). Despite this, there are uncertainties about how muscle mass, lower extremity muscular strength, and BMD are related. We examined the impact of lower extremity muscle strength and mass on BMD in the general American population using cross-sectional analysis. Methods In the study, we extracted 2165 individuals from the National Health and Nutrition Examination Survey 1999–2002. Multivariate logistic regression models were used to examine the association between muscle strength, muscle mass, and BMD. Fitted smoothing curves and generalized additive models were also performed. To ensure data stability and avoid confounding factors, subgroup analysis was also conducted on gender and race/ethnicity. Results After full adjustment for potential confounders, significant positive associations were detected between peak force (PF) [0.167 (0.084, 0.249) P < 0.001], appendicular skeletal muscle index (ASMI) [0.029 (0.022, 0.036) P < 0.001], and lumbar spine BMD. A positive correlation was also found between PF, ASMI, and pelvis and total BMD. Following stratification by gender and race/ethnicity, our analyses illustrated a significant correlation between PF and lumbar spine BMD in both men [0.232 (0.130, 0.333) P < 0.001] and women [0.281 (0.142, 0.420) P < 0.001]. This was also seen in non-Hispanic white [0.178 (0.068, 0.288) P = 0.002], but not in non-Hispanic black, Mexican American and other race–ethnicity. Additionally, there was a positive link between ASMI and BMD in both genders in non-Hispanic whites, and non-Hispanic blacks, but not in any other racial group. Conclusion PF and ASMI were positively associated with BMD in American adults. In the future, the findings reported here may have profound implications for public health in terms of osteopenia and osteoporosis prevention, early diagnosis, and treatment.
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