| ObjectiveThis study is divided into three parts.The first part established a risk assessment model for osteopenia in chronic hepatitis B(CHB)patients based on screening and identification of risk factors for osteopenia in CHB patients.This will provide a scientific basis for the risk prediction of osteopenia in CHB.The second part summarized the distribution characteristics of traditional Chinese medicine(TCM)syndrome of osteopenia in CHB patients.The correlation with objective indicators such as bone mineral density(BMD)and fracture risk assessment tool(FRAX)was also explored.It can provide the basis of syndromes for the early prevention and treatment of reduced BMD in CHB patients.The third part evaluated the efficacy and safety of the Shugan-Jianpi-Yishen formula combined with antiviral therapy objectively.It can provide an objective basis for optimizing the clinical treatment plan of CHB patients.Methods1 Establishment of a risk assessment model for osteopenia in CHBIn this retrospective study,consecutive CHB patients with or without osteopenia were enrolled from January 2019 to December 2020 in the Department of Hepatology,Guangdong Provincial Hospital of Chinese Medicine.The included patients were divided into a modeling group and a validation group at a ratio of 7:3 randomly.The univariate analysis was used to identify the risk factors of osteopenia in CHB preliminarily in the modeling group.Group Lasso-Logistic regression was conducted to determine the independent risk factors for BMD loss in CHB.The correlation between each predictor and osteopenia in CHB and the estimated coefficients of the parameters were determined.A risk assessment model for osteopenia in CHB was established,and a Nomogram was generated to visualize the model.The discrimination,calibration,and clinical utility of this model in the modeling and validation groups were evaluated by the area under the receiver operating characteristic curve(AUC),calibration curve,and decision curve analysis.2 Study on the TCM syndromes in CHB patients with osteopeniaThis part is a case series analysis study.Consecutive CHB patients with osteopenia who attended the Department of Hepatology,Guangdong Provincial Hospital of Chinese Medicine,were enrolled from January 2019 to July 2021.Data were collected on patients’TCM,BMD,FRAX,and other clinical data.The characteristics of the TCM syndrome distribution of osteopenia in CHB patients were summarized.And its correlation with objective indicators such as BMD and FRAX was discussed.3 Curative effect evaluation of Shugan-Jianpi-Yishen formula on CHB with osteopeniaThis part is a prospective observational study.Patients were selected from January 2021 to July 2021 in the Department of Hepatology,Guangdong Provincial Hospital of Chinese Medicine.Patients were divided into the combined TCM and western medicine group and western medicine group based on whether use the Shugan-Jianpi-Yishen formula or not.The western medicine group was treated with standard antiviral therapy.The combined TCM and western medicine group was treated with Shugan-Jianpi-Yishen formula plus antiviral therapy,with a complete course of 24 weeks.The efficacy and safety of the Shugan-Jianpi-Yishen formula plus antiviral therapy were evaluated by analyzing the effect on BMD and bone metabolism.Results1 Establishment of a risk assessment model for osteopenia in CHB1.1 Basic informationA total of 682 CHB patients were enrolled,477 in the modeling group and 205 in the validation group after randomization.1.2 Results of Group Lasso-Logistic Regression AnalysisAfter analysis by Group Lasso-Logistic,the results showed that a higher age[odds ratio(OR),1.558;P<0.001],hypertension(OR,3.002;P=0.016),cirrhosis(OR,5.802;P<0.001),the use of antiviral drugs ADV or TDF(OR,2.684;P=0.034),higher serum HDL-C levels(OR,1.466;P=0.046),and lower serum TSH levels(OR,0.882;P<0.001)were independent risk factors in CHB patients with osteopenia.1.3 Construction and evaluation of the regression model W for risk assessment of osteopenia in CHBThe Group Lasso-Logistic model equation for the risk assessment of osteopenia in CHB was:P=-5.958+0.104*age+1.099*hypertension+1.758*cirrhosis+0.987*use of antiviral drug ADV or TDF+0.832*serum HDL-C level-0.716*serum TSH level.The model W had good discrimination(AUC:the modeling group,0.857;the validation group,0.882),calibration,and clinical utility in both the modeling group and the validation group.2 Study on the TCM syndromes in CHB patients with osteopenia2.1 Basic situationA total of 300 patients were enrolled in this part,with a median age of 51.00(42.00,57.00)years old,and males accounted for 71.00%.2.2 Distribution of TCM syndrome typesThe order of TCM syndrome types of the included patients was:liver stagnation and spleen deficiency syndrome>liver and kidney yin deficiency syndrome>blood stasis blocking collaterals syndrome>liver and gallbladder damp-heat syndrome>spleen and kidney yang deficiency syndrome.Liver stagnation and spleen deficiency syndrome,liver-kidney yin deficiency syndrome,and blood stasis blocking collaterals syndrome were the most common,accounting for 61.34%,14.00%,and 12.33%,respectively.2.3 Discussion on the association between TCM syndrome types and objective indicatorsDiscussion on the association between TCM syndrome types and BMD:The differences in left femoral neck BMD and lumbar spine L1-4 BMD levels among different TCM syndromes types were statistically significant.Among them,left femoral neck BMD in patients with liver and kidney yin deficiency syndrome and spleen and kidney yang deficiency syndrome was significantly lower than that of liver and gallbladder damp-heat syndrome(0.62 vs.0.68,0.61 vs.0.68,all P<0.05)and liver stagnation and spleen deficiency syndrome(0.62 vs.0.69,0.61 vs.0.69,all P<0.05).The lumbar spine L1-4 BMD in patients with liver and kidney yin deficiency syndrome and spleen and kidney yang deficiency syndrome was significantly lower than that in liver stagnation and spleen deficiency syndrome(0.83 vs.0.87,0.81 vs.0.87,all P<0.05)and liver and gallbladder damp-heat syndrome(0.83 vs.0.86,0.81 vs.0.86,all P<0.05).Discussion on the association between TCM syndrome types and FRAX:The 10-year probability of major osteoporotic fracture and the 10-year probability of major osteoporotic fracture was significantly different among the TCM syndrome types.The 10-year probability of major osteoporotic fracture was higher in patients with the liver and kidney yin deficiency syndrome and spleen and kidney yang deficiency syndrome than in patients with the liver and gallbladder damp-heat syndrome(2.90 vs.2.30,3.65 vs.2.30,all P<0.05)and liver stagnation and spleen deficiency syndrome(2.90 vs.2.20,3.65 vs.2.20,all P<0.05).The 10-year probability of hip fracture was significantly higher in patients with liver and kidney yin deficiency syndrome and spleen and kidney yang deficiency syndrome than in patients with liver and gallbladder damp-heat syndrome(1.10 vs.0.50,1.20 vs.0.50,all P<0.05),liver stagnation and spleen deficiency syndrome(1.10 vs.0.40,1.20 vs.0.40,all P<0.05),and blood stasis blocking collaterals syndrome(1.10 vs.0.60,1.20 vs.0.60,all P<0.05).Discussion on the association between TCM syndrome types and laboratory indexes:The ALT and AST levels were significantly higher in the liver and biliary damp-heat syndrome than in liver stagnation and spleen deficiency syndrome.The TSH levels of patients with spleen and kidney yang deficiency syndrome were lower than those of blood stasis blocking collaterals syndrome.The S-Ca levels were significantly lower than those of all other syndromes(all P<0.05).3 Curative effect evaluation of Shugan-Jianpi-Yishen formula on CHB with osteopenia3.1 Basic informationA total of 60 patients were included,30 each in the combined TCM and western medicine group and the western medicine group.Three patients were lost after 12 weeks(two in the western medicine group and one in the combined TCM and western medicine group).The mean age was 47.83±9.58 years old,and 77.19%were male.There were no significant differences in age and gender composition between the two groups,which were comparable.3.2 Curative effect evaluationIn the evaluation of BMD,the left femoral neck BMD in the combined TCM and western medicine group increased after treatment compared with that before treatment(0.72 vs.0.68,P<0.001).In contrast,the left femoral neck BMD of the western medicine group decreased(0.68 vs.0.71,P<0.001).After treatment,the BMD of the left femoral neck improved more in the combined TCM and western medicine group than in the western medicine group(P<0.001).There was no statistical difference in the lumbar spine L1-4 BMD within and between groups after treatment(P>0.05).In terms of improvement in the proportion of abnormal bone mass,the proportion of abnormal left femoral neck BMD in the combined TCM and western medicine group decreased from 80.00%to 65.52%,while that in the western medicine group increased from 73.33%to 89.29%.The difference between the two groups was statistically significant(P=0.028).There was no significant difference in the proportion of the abnormal bone mass of the lumbar spine L1-4 between the two groups after treatment(P=0.243).In terms of FRAX,the 10-year probability of major osteoporotic fracture(1.97 vs.2.35,P<0.001)and the 10-year probability of hip fracture(0.45 vs.0.70,P<0.001)in the combined TCM and western medicine group decreased compared with before treatment.The 10-year probability of major osteoporotic fracture(2.52 vs.2.18,P<0.001)and the 10-year probability of hip fracture(0.65 vs.0.50,P<0.001)in the western medicine group increased.Compared with the western medicine group after treatment,the 10-year probability of major osteoporotic fr-acture and the 10-year probability of hip fracture in the integrative Chinese and western medicine groups were significantly lower(all P<0.001).In terms of bone metabolism index,the serum PINP level in the combined TCM and western medicine group was significantly higher than before treatment after treatment(P=0.008).The level of PINP in the western medicine group was significantly lower than that before treatment(P=0.0017).After treatment,the difference in PINP levels before and after treatment in the combined TCM and western medicine group was significantly higher than that of the cohort of western medicine(P<0.001).There were no significant differences in other bone metabolism indexes within and between groups after treatment(all P>0.05).In terms of glycolipid metabolism indexes,the western medicine group had higher total cholesterol levels(P=0.009).There were no significant differences in other glycolipid metabolism indexes within and between groups after treatment(all P>0.05).There were no serious adverse reactions in both groups.There was no statistical difference in the incidence of abnormal creatinine(all P>0.05).Conclusion1.Older age,history of hypertension,history of cirrhosis,use of antiviral drugs ADV or TDF,lower serum TSH level,and higher serum HDL-C level are independent risk factors for osteopenia in CHB patients.To prevent further disease progression,it is necessary to strengthen the screening for the above risk factors related to BMD reduction in CHB patients and correct the modifiable risk factors.2.The risk assessment model of osteopenia in CHB constructed by Group Lasso-Logistic regression had a good risk prediction ability,which can better identify the high-risk population of BMD reduction in CHB patients.3.The most common TCM syndrome types in CHB patients with osteopenia were liver stagnation and spleen deficiency syndrome,followed by liver and kidney yin deficiency syndrome and blood stasis obstructing collaterals syndrome,suggesting that the pathogenesis of this disease is closely associated with liver,spleen,and kidney.Liver and kidney yin deficiency syndrome and spleen and kidney Yang deficiency syndrome were related to lower BMD and higher fracture risk.The pathogenesis was liver stagnation,spleen deficiency,kidney deficiency,and blood stasis.Attention should be paid to the TCM dialectical protection to reduce the occurrence of osteoporosis and fracture.4.Shugan-Jianpi-Yishen formula can increase the femoral neck BMD of CHB patients with osteopenia,regulate the level of bone metabolism index PINP,reduce the risk of hip and major osteoporotic fractures,shorten the course of treatment,and has good safety. |
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