The Effects Of Denosumab On Bone Metabolism And Glucose And Lipid Metabolism On Postmenopausal Osteoporosis

Objective The purpose of the study is to investigate the effects of denosumab on bone mineral density,bone metabolism,glucose and lipid metabolism on postmenopausal osteoporosis women,and to explore the and efficacy and safety of denosumab in the treatment of postmenopausal osteoporosis（PMOP）.Methods⑴Non-diabetic postmenopausal women admitted to the Affiliated Hospital of Qingdao University from Oct,2020 to Dec,2022 and diagnosed as PMOP,who were treated with denosumab were included in the study.Exclude the following:A history of diabetes or a diagnosis of diabetes during treatment;A history of lipid metabolism disorder such as family hypercholesterolemia,taking statins,niacin,ezetimibe and other drugs that regulate lipid metabolism;Clinical date were not available;Extensive usage of hormone in the past;Used other anti-osteoporosis drugs excluded denosumab;Patients with parathyroid diseases,Cushing syndrome,rheumatoid arthritis,osteomalacia and other bone diseases;Patients with cognitive impairment or mental illness,malignant tumors,chronic organ insufficiency and other chronic diseases;Except that,The diet should be consistent as same as possible during the treatment,without major changes;All patients were given enough calcium tablets and vitamin D according to the monitoring level;The dose of other oral medications remained unchanged during treatment;No second anti-osteoporosis drug was used during treatment.⑵Take a collection of baseline materials,and date at 3,6,12 months after treatment.Make statics analysis after that.Materials included:height,weight,fasting blood glucose,fasting insulin,fasting C-peptide,glycated hemoglobin,low density cholesterol,high density cholesterol,triglyceride,total cholesterol,alanine transaminase,aspartate aminotransferase,glutamyl transpeptidase,total bone mineral density（lumbar vertebra,femoral neck,hip）,bone turnover biomarkers（P1NP,βCTX）,calcium,phosphorus,parathyroid hormone,25-（OH）D₃,and calculate the index below:BMI=W/H2（kg/m2）,insulin resistance:HOMA-IR=FBG×Fins/22.5,the function ofβcell in islet:HOMA-β=20×Fins/（FBG-3.5）,atherosclerotic index:AI=（TC-HDL）/HDL.⑶SPSS 26.0software was used for statistical analysis,and the collected indicators were tested for normality,which were compared with baseline data at the same time.Paired sample t-test was used for homogeneity of variances,and rank sum test was used for heterogeneity of variances.⑷All hypothesis tests were two-sided,and P<0.05 was considered statistically significant.⑸To investigate the effects of denosumab on insulin resistance index,pancreaticβcell function,atherosclerosis index,glucose and lipid metabolism index and bone mineral density in postmenopausal women with osteoporosis.⑹The patients were grouped according to different criteria to analyze whether there were differences in glucolipid metabolism between different subgroups of denosumab,and whether the differences were statistically significant.Results⑴The baseline data of 107 patients and the indexes of glucose and lipid metabolism and bone metabolism after treatment were successfully collected.⑵Denosumab in the treatment of postmenopausal women with osteoporosis showed no significant difference in fasting blood glucose at 3 and 6 months after treatment（5.24±0.60 vs 5.36±0.67mmol/L,P=0.065;5.22±0.15 vs 5.36±0.67mmol/L,P=0.053）,but decreased at 12 months after treatment,the difference was statistically significant（5.10±0.72 vs 5.36±0.67mmol/L,P=0.023）.HOMA-IR decreased from baseline（2.62±1.22）at3,6 and 12 months after denosumab treatment（2.27±1.30 vs 2.62±1.22,P=0.031;2.01±0.98 vs 2.62±1.22,P<0.001;2.13±1.01 vs 2.62±1.22,P<0.001）.⑶The changes of lipid metabolism index,atherosclerosis index and BMI at 3 months,6 months and 12months after treatment were not statistically significant.There was no significant change in liver function（ALT,AST,GGT）after medication,and the results were still not statistically significant after repeated analysis.⑷After 3 months,6 months and 12 months of denosumab treatment,the bone mineral density of femoral neck and hip was significantly increased compared with baseline,the difference was statistically significant.After 6months of treatment,lumbar vertebra bone mineral density decreased by 4.14%compared with baseline,but the difference was not statistically significant（P=0.053）.After 3 months and 12 months,the lumbar vertebra bone mineral density increased by 0.75%and 0.63%compared with baseline,respectively.Bone turnover biomarkers had a significant improvement from baseline after 3 months,6 months and 12 months of denosumab treatment（P1NP:36.272±3.380 vs 52.076±4.262ng/ml,32.978±6.940 vs 52.076±4.262ng/ml,27.854±8.235 vs 52.076±4.262ng/ml,all P≤0.05;βCTX:0.360±0.525 vs0.681±0.482ng/ml,0.309±0.216 vs 0.681±0.482ng/ml,0.353±0.267 vs 0.681ng/ml±0.482,all P≤0.05）.All of them were statistically significant.⑸No serious drug associated adverse reaction happened in the treatment of PMOP with denosumab.Conclusion This study verified the effect of denosumab on bone mineral density improvement in postmenopausal women,earlier is better.There are no severe adverse reactions occurred.Denosumab can improve insulin resistance and blood glucose in postmenopausal osteoporosis patients,but has no significant effect on liver function and lipid metabolism.