Correlation Analysis Between Senile Osteoporosis And Thyroid Function

Objective:As the global population ageing,as a common degenerative disease incidence of osteoporosis is rising,it has become a major global health problem.As an essential factor in maintaining bone structure and strength,thyroid hormone may become a risk factor for bone disease when thyroid dysfunction occurs.However,the role of excessive or insufficient thyroid hormone in the pathogenesis of senile osteoporosis and fracture risk factors has been underestimated,few studies have been conducted,and its underlying pathogenesis remains unclear.This study aims to explore the association between osteoporosis and thyroid function in the elderly with the help of clinical data analysis and bioinformatics data.Methods:Clinical data were collected from 130 elderly patients with an average age of 70.35 years who underwent a bone mineral density examination and thyroid function tests while being treated in the China-Japan Union Hospital of Jilin University between January 2020 and November 2022 were chosen.They included 32 men and 98 women with ages ranging from 60 to 92 years.They were split into three groups based on the WHO standard: normal bone mass,osteopenia,and osteoporosis.There were 18 cases in normal bone mass bunch(counting6 males and 12 females),53 cases in osteopenia bunch(counting 12 males and 41 females),and 59 cases in osteoporosis bunch(counting 14 males and 45 females).The general information of all the selected research objects was collected,including age,gender,height and weight,etc.At the same time,the five test indicators of thyroid function during admission were recorded.Thyroid stimulating hormone,free triiodothyronine,free thyroxine,triiodothyronine and thyroxine,as well as T-score of lumbar spine,left hip joint and right hip joint in bone mineral density examination were included.After data integration,SPSS25.0 statistical analysis software was used for data analysis.Continuous variables conforming to normal distribution were represented by mean and standard deviation;comparison between two groups was performed by T test;comparison between multiple groups was performed by variance analysis and multiple comparisons.The skewness distribution continuous variables were represented by median and quartile spacing.Mann-Whitney U test was used for comparison between the two groups,and Kruskal-Wallis H test was used for multi-component comparison.Counting data were compared by chi-square test.Spearman correlation analysis was used for correlation analysis.The influencing factors of osteoporosis were analyzed by logistic regression and Hosmer-Lemeshow test was used to judge the fit degree of the model.The factors influencing the qualitative identification of osteoporosis were analyzed by ROC and the specificity,sensitivity and area under the curve(AUC)were calculated(P<0.05 was considered statistically significant).DEGs were screened from the public GEO database that was used to pick the gene expression profile of the senile osteoporosis in the GSE35958 dataset that including 9 bone marrow samples,including 5 cases of primary senile osteoporosis and 4 age-matched controls.And the target genes of osteoporosis,hyperthyroidism,hypothyroidism,subclinical hyperthyroidism and subclinical hypothyroidism were screened by human disease database.After integration and mapping,the intersection of four diseases of senile osteoporosis and thyroid dysfunction was taken to obtain the common target genes,and functional enrichment analysis was performed by R software.The Protein-Protein Network Interaction of Common Target Genes Interaction Networks(PPI)was then built using the Search Tool for the Retrieval of Interaction Gene/Proteins(STRING),and Cytoscape software was used to screen the hub genes.Result:1.Among 130 clinical samples,13.85% had normal bone mass,40.77% had osteopenia,and 45.38% had osteoporosis.There were significant differences in age,BMI,TSH,FT3,FT4,T3,T4,lumbar T value,left hip joint T value and right hip joint T value among normal bone mass,osteopenia and osteoporosis groups(P<0.05).Compared with the normal bone mass group,there were statistical differences in age,TSH,FT3,FT4,T3,T4,T values of lumbar spine,T values of left hip joint and T values of right hip joint in the osteopenia group(P<0.05).Compared with the normal bone mass group,there were significant differences in age,TSH,FT3,FT4,T3,T4,T values of lumbar spine,T values of left hip joint and T values of right hip joint in osteoporosis group(P<0.05);Compared with the osteopenia group,there were statistically significant differences in BMI,lumbar T value,left hip joint T value and right hip joint T value in the osteoporosis group(P<0.05).2.TSH levels of the five indicators of thyroid function in elderly patients were negatively correlated with T values of the left and right hip joints(r=-0.243and-0.231,respectively).FT3 level was positively correlated with T value of left and right hip joints(r =0.299 and 0.289,respectively).The FT4 level was positively correlated with the T value of the left and right hip joints(r = 0.190 and 0.197,respectively).T3 level was positively correlated with the T value of the left and right hip joints(r= 0.294 and 0.285,respectively).The T4 level was positively correlated with the T value of the left and right hip joints(r = 0.247 and 0.232,respectively),and all the differences were statistically significant(P<0.05).3.In logistic regression analysis,FT3 level was found to be the influencing factor of osteoporosis in elderly patients,OR was0.910(0.859-0.964),Hosmer-Lemeshow test P=0.499,indicating a good fitting degree of the model.The results of ROC analysis of osteoporosis and FT3 level in elderly patients showed that the specificity,sensitivity and AUC were 84.7,61.6 and 0.751,respectively,and the differences were statistically significant(P<0.05).4.30 common target genes were obtained by matching mapping between osteoporosis and four diseases of thyroid dysfunction,including hyperthyroidism,hypothyroidism,subclinical hyperthyroidism,and subclinical hypothyroidism.The top five core genes were ALB,TNF,VEGFA,CRP and CD4.Target gene enrichment analysis showed that they were mainly enriched in the external side of plasma membrane,coated vesicle membrane,plasma lipoprotein particle,lipoprotein particle and protein-lipid complex,and had molecular functions such as exogenous protein binding,virus receptor activity,receptor ligand activity,signaling receptor activator activity and lipoprotein particle binding.It is involved in such biological processes as regulation of cell-cell adhesion,regulation of leukocyte cell-cell adhesion,adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains,positive regulation of leukocyte cell-cell adhesion and regulation of hemopoiesis.It is also regulated by signaling pathways such as Type I diabetes mellitus,Human T-cell leukemia virus 1 infection,Allograft rejection and Graft-versus-host disease.Conclusion:1.According to different bone mineral density T values,the level distribution of age,BMI,TSH,FT3,FT4,T3 and T4 was different.TSH level was negatively correlated with T value of left and right hip joints,while FT3,FT4,T3 and T4 levels were positively correlated with T value of left and right hip joints.Moreover,FT3 level can be used as an influential factor for osteoporosis in elderly patients.2.There are a certain number of common target genes in the gene database network between the four diseases related to elderly osteoporosis and thyroid dysfunction,among which the top five core genes ALB,TNF,VEGFA,CRP and CD4 are particularly closely related to the diseases,providing a new direction for exploring the pathogenesis and therapeutic targets.