| Study Background and Objective:Fracture is a worldwide widespread clinical problem that endangers people’s health.It has serious harm,high treatment cost and high incidence,which is on the rise.According to global burden of disease data,there were 178 million new fractures worldwide in 2019,and the loss of Disability Adjusted Life Years(YLDs)due to fractures was about 25 million.Low bone density and osteoporosis(OP)account for a large proportion of fracture patients,and the disease burden caused by most fractures can be reduced by preventing osteoporosis.Early onset of osteoporosis is insidious and asymptomatic,and osteoporosis is often diagnosed at the time of the first fracture.Therefore,early assessment of an individual’s risk of osteoporosis is very important to prevent the first fracture.Anemia is the most common hematological disease.The global burden of disease in 2016 indicates that anemia patients account for about 27% of the global population,and the incidence of anemia in any country in the world is greater than 10%.Previous studies have shown that anemia is associated with several chronic diseases,and in recent years studies have shown that anemia may be a potential predictor of osteoporosis risk.It should be noted that women are more likely to develop low bone density or osteoporosis than men due to their low bone density,small bone geometry,and low muscle mass.At the same time,women are more prone to anemia due to special physiological stages such as menstrual period,pregnancy and abnormal uterine bleeding.Therefore,it is necessary to pay attention to anemia and low bone mineral density or osteoporosis in female population,and to explore the relationship between anemia and osteoporosis.At present,the related research on the association between anemia and osteoporosis focuses on some specific disease populations,such as patients with type 2 diabetes mellitus and rheumatoid disease,and on natural populations,such as the elderly population,adult male population and postmenopausal women.As for the female population,the existing studies mainly focus on the postmenopausal population,and there is no consistent study conclusion,and there is a lack of studies on the whole female population or premenopausal female population.The decrease of bone mineral density and osteoporosis is a chronic and continuous process,which may occur in various stages of female population in their lives.Premenopausal women may have changes in bone trabecula.Only paying attention to some female populations may not fully reflect the relationship between anemia and bone mineral density and osteoporosis in the whole female population.Therefore,it is necessary to explore whether there is a correlation between anemia and osteoporosis in the whole female population and premenopausal and postmenopausal population,so as to supplement the existing research conclusions and provide evidence support for the early prevention of low bone mineral density and osteoporosis.According to the diagnostic criteria established by WHO,hemoglobin is the gold standard for the diagnosis of anemia.In addition,other blood indicators related to anemia(such as red blood cell count and its related parameters(hematocrit,mean corpuscular volume,mean corpuscular hemoglobin,red blood cell distribution width,platelets,serum ferritin,etc.)can also evaluate and reflect the severity of anemia and the type of anemia from various aspects.Compared with bone mineral density measurement,blood indicators have the advantages of being simpler,more economical and covering a wider population.Combined with its advantages,if it can be confirmed that it is associated with bone mineral density and osteoporosis,it can be used as a potential risk prediction for low bone mineral density and early osteoporosis.Therefore,based on the data of National Health and Nutrition Examination Survey(NHANES),this study first understood the distribution of anemia and bone mineral density(femoral neck and spine)in female population,and then explored the association between anemia and bone mineral density and low bone mineral density in all female population.Meanwhile,the female population was divided into pre-menopausal and post-menopausal population for subgroup analysis.Finally,considering that objective blood indicators related to anemia such as red blood cell count can sensitively reflect the relationship between anemia and bone mineral density,this study also explored the relationship between anemia related blood indicators and bone mineral density in all women and different menstrual status populations.This study can supplement the existing research evidence of the association between anemia and bone mineral density,and then move forward the prevention and control of low bone mineral density and osteoporosis,prevent the occurrence of serious fracture events,and provide reference for saving medical resources and rational allocation of resources.Study Population and Data:The data for this study were derived from the NHANES data published by United States Centers for Disease Control and Prevention,a large population-based cross-sectional survey designed to collect information on diet,nutritional status,health,and health behaviors of adults and children in the United States.In this study,5 2-year cycle data(2005-2006,2007-2008,2009-2010,2013-2014 and 2017-2018)from NHANES database will be selected,and a final total of 6582 people will be included in this study through reasonable inclusion and exclusion criteria.Methods and Contents:Firstly,the data of anemia,blood parameters,BMD T score,low BMD and covariates(including demographic data,lifestyle,family history)were analyzed descriptively in the whole female population and premenopausal and postmenopausal women.In the descriptive analysis,the measurement data is expressed as mean ± SD or median [quartile],and the categorical data is expressed as percentage.For the measurement data,t test or Kruskal-Wallis rank sum test is used to judge whether the difference between groups is statistically significant,and for the categorical data,chi-square test is used to judge whether the difference between two groups is statistically significant.Secondly,on the premise of reasonable potential confounding through causality diagram,the association between anemia and anemia severity(mild,moderate,severe)and low bone mineral density in the whole female population and premenopausal and postmenopausal subgroups was explored through multiple Logistic regression model.In addition,multiple linear models were used to estimate the association of anemia severity and its associated blood parameters with bone mineral density T-values.Finally,a series of sensitivity analyses were performed to verify the robustness of the association between anemia and BMD in the main analysis by changing the inclusion and exclusion criteria and adjusting the inclusion of model confounding.Results:(1)Descriptive analysis:(1)In the overall female population,anemia accounted for 10.4%;The proportion of low bone mineral density was 35.3%(femoral neck)and 28.4%(spine)according to different bone mineral density measurement sites.(2)Compared with premenopausal women,postmenopausal women had a higher proportion of low bone mineral density and a lower proportion of anemia,and the difference between the two groups was statistically significant.(3)Compared with premenopausal women,in postmenopausal women,except platelet count,other anemia related blood indicators were higher,and the differences were statistically significant.The most significant difference was in the amount of ferritin,which was 48.22 ng/m L and 138.35 ng/m L in premenopausal and postmenopausal women,respectively.(2)Results of correlation analysis:(1)The correlation between anemia and low bone mineral density: In women overall,anemia was inversely associated with the risk of low BMD(femoral neck: OR:0.720;95%CI:0.568～0.914;Spine: OR:0.699;95%CI: 0.537～0.911).In premenopausal women,anemia was inversely associated with the risk of low bone mineral density(femoral neck: OR: 0.600;95%CI:0.405～0.888;Spine: OR: 0.633;95%CI: 0.424～0.945).In postmenopausal women,anemia was not associated with low bone mineral density.(2)The correlation between the severity of anemia and low bone mineral density: In the overall female population,mild anemia was inversely associated with the risk of low BMD(femoral neck BMD T-score)(OR:0.658;95%CI:0.493～0.878),and the correlation was statistically significant.The same trend was observed in other populations and subgroups,but it was not statistically significant.(3)The correlation between anemia severity and bone mineral density T value: In the overall female population,there was a positive correlation between mild anemia and the T score(femoral neck: β: 0.172;95%CI:0.078～0.266;Spine:β: 0.215;95%CI: 0.086～0.344).In premenopausal women,there is a positive correlation between mild anemia and the T value(femoral neck: β: 0.204;95%CI:0.075～0.333;Spine:β: 0.235;95%CI: 0.084～0.387).In the whole female population and premenopausal female population,the relationship between moderate and severe anemia and bone mineral density T value has a positive correlation trend.In postmenopausal women,there was also a positive correlation between mild and moderate anemia and BMD T value,but the correlation was not statistically significant.In the postmenopausal population,there was a trend toward a negative association between severe anemia and BMD T-scores,but the association was not statistically significant.(4)The correlation between anemia related blood indexes and bone mineral density(BMD)T value: Hemoglobin,hematocrit and BMD T value were negatively correlated in different bone mineral density measurement sites in the whole female population and premenopausal female population,and the correlation was statistically significant.Red blood cell count,ferritin and bone mineral density T value in the whole female population and premenopausal female spine bone mineral density measurement showed negative correlation,and the correlation was statistically significant.Mean corpuscular volume was negatively correlated with bone mineral density(BMD)T value in the whole female population and premenopausal female population,and the difference was statistically significant.Mean corpuscular hemoglobin and bone mineral density T value in premenopausal women femoral neck bone mineral density measurement was negatively correlated,and the difference was statistically significant.There was no significant correlation between red blood cell distribution width,platelets and bone mineral density T value.Conclusions:In the overall female population and premenopausal women,results showed that anemia was associated with a lower risk of low bone mineral density,and that mild anemia in the severity of anemia was associated with a higher bone mineral density T-score.Decreased hemoglobin,hematocrit,red blood cell count,serum ferritin,and mean red blood cell volume were associated with higher bone mineral density T value.In contrast,in postmenopausal women,there was no significant correlation between anemia,anemia severity,and blood indicators related to anemia and bone mineral density.Therefore,anemia may have a protective effect on low bone mineral density,and anemic-related blood indexes have certain predictive significance on bone mineral density decline.However,this effect and significance may be different in different physiological stages,different bone mineral density measurement sites and different severity of anemia in female population.In the future,more randomized controlled trials,animal trials,or causal inference studies based on the framework of potential outcomes are needed to further clarify the causal association between anemia and bone mineral density. |
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