The Association Study Between Fluorescent Oxidation Products(FlOPs) And Osteoporotic Fractures

Background:Fluorescent oxidation products（FlOPs,excitation/emission wavelength 320/420 nm,expressed as FlOP₃20;360/420 nm[FlOP₃60];400/475 nm[FlOP₄00]）are new biomarkers that comprehensively reflect oxidative stress damage.Some studies have shown that oxidative stress is an independent risk factor for osteoporosis,but the evidence of the association between FlOPs and osteoporosis fracture is still limited.Purpose:The purpose of this study was to further clarify the impact of oxidative stress on osteoporotic fracture by exploring the association between the FlOP levels of patients with osteoporotic fracture（including hip and non-hip fractures）and the control population in the Chinese population and osteoporotic fracture,so as to provide theoretical reference for the more sensitive and accurate evaluation of bone health and prevention and treatment of osteoporotic fracture in the future.Methods:The case group were new low traumatic fracture cases aged 50 and above in the orthopedics department of the Second Hospital of Jilin University,and the control group were healthy non-fracture population aged 50 and above from the Changchun community,excluding cases with pathological fracture and incomplete fracture information,secondary osteoporosis related diseases and participants who used osteoporosis related drugs in the present or the past.Cases were individually matched with controls by age（±4 years）and sex at a 1:2 ratio,and finally 44 cases and 88 controls were included in the study.In addition,we also conducted a sensitive unmatched case-control test,which included all fracture cases and all eligible nonfracture controls（434）before matching.We used the method introduced in the previous literature to measure plasma FlOPs.The baseline characteristics and the level of FlOPs in the case and control groups were analyzed by t test,Wilcoxon test and χ2 test.In the matched case control study,univariate and multivariate conditional logistic regression models were used to analyze the association between FlOPs（one standard deviation for each increase in the logarithmic scale）and fractures,and the model was adjusted using BMI,physical activity,and milk intake frequency>1 time/week.These factors had significant association with osteoporotic fractures atα<1.After that,a subgroup analysis of fracture types（hip fractures and non-hip fractures）was conducted,using the same covariate adjustment model as described above.Finally,two-way interaction item（physical activity*FlOPs and milk intake frequency>1 time/week*FlOPs）was analyzed to test whether physical activity and milk intake frequency>1 time/week modified the association between FlOPs and fractures.In addition,the unconditional logistic regression model was used to analyze the unmatched case control study,which was to test the reliability of matched research results.We also used all factors to adjust the model.All statistical analyses were conducted using SPSS software.Results:1.In the matched case-control study,in the fracture group,the average age of participants was 68.2 years old,and the control group had similar average age.In the fracture and control groups,women account for 75%.In the fracture group,the average level of BMI was 23.5 kg/m2,which was not significantly different from that in the control group（24.9 kg/m2）（P=0.056）.Compared with the median level of physical activity in the control group（35.0 MET hours/week）,the median level of physical activity of the fracture group was significantly lower（35.0 MET hours/week）（P<0.001）.There were 31 people（70%）had the frequency of milk intake>1/week in the fracture group,the proportion was significantly lower compared with that of the control group（77 people,87%）（P=0.017）.Other research factor distributions did not show significant difference in the two groups,such as age,sex,smoking,calcium supplements,history of coronary heart disease,history of type II diabetes,history of stroke,height decrease>3cm after age 40,family history of osteoporosis and fracture.In the unmatched case-control study,in the control group,the average age was 64.7,significantly lower compared with the age of the fracture group（P=0.041）.In the control group,women account for 58%,the proportion was significantly lower than that of the fracture group（P=0.035）.In the control group,the average BMI was 24.9 kg/m2,the level of BMI was significantly higher compared with that in the fracture group（P=0.016）.The difference in the distribution of other factors in the two groups was similar to that in the matched case-control study.2.In the matched case-control study,the median level of FlOP₃20 for the fracture group population was 127.0 FI/ml,significantly lower compared with the level of the control group FlOP₃20（141.4 FI/ml）（P=0.023）;the median level of FlOP₃60 was 121.0 FI/ml,significantly higher compared with the level of the control group FlOP₃60（112.5 FI/ml）（P=0.005）;the median level of FlOP₄00 was 39.5FI/ml,significantly higher compared with the level of the control group FlOP₄00（33.5 FI/ml）（P<0.001）.In the unmatched case-control study,the difference of FlOP levels between fracture group and control group was similar to that of matched case-control study.3.In the matched case-control study,the results of multi-factor logistic regression showed that there was a significant positive association between FlOP₄00 with osteoporosis fracture（OR=20.573,95%CI=1.972-214.631,P=0.012）.In the unmatched controlled case-control study,there was still a significant positive association between FlOP₄00 and osteoporosis fracture（OR=3.777,95%CI=2.4955.718,P<0.001）.4.It was found that in subgroup analysis,in the matched case-control study,there were significant positive associations between FlOP₄00 with hip fracture（OR=6.195,95%CI=2.074-18.505,P=0.001）and non-hip fracture（OR=4.489,95%CI=1.848-10.902,P=0.001）.In unmatched case-control study,there were still significant positive associations between FlOP₄00 with hip fracture and non-hip fracture,and the OR value was close to.5.The two-way interaction results showed that,the physical activity level and the frequency of milk intake>1/week had no effect modification on the association between FlOP₄00 with osteoporosis fracture in matched and unmatched case-control studies（All P interaction>0.05）.Conclusion:Through matched and unmatched case-control studies,the following conclusions were reached:1.In this study population,low BMI level,low physical activity level and low milk intake frequency were risk factors of osteoporosis fracture.2.In this study population,there were positive associations between FlOP₄00 with osteoporosis fracture,and there is no interaction between FlOP₄00 with physical activity level and milk intake frequency,which indicated that FlOP₄00 may be a biomarker for osteoporosis fracture,and oxidative stress may be an independent risk factor for osteoporotic fractures..3.The impact of oxidative stress on the risk of osteoporosis fracture maybe did not depend on body parts.