| Osteoporosis is a progressive skeletal disease characterized by low bone mineral density(BMD)with a consequent increase in bone fragility and susceptibility to fracture risk.Although,the most widely used method is the clinical definition proposed by the World Health Organization(WHO)in 1994,which is defined as bone mineral density(BMD: measured in g/cm~2)measurements in women that have fallen by more than 2.5 standard deviations(SDs)below the young average value.Also,pain,kyphosis,loss of height,and a history of fragility fracture are used as operational definitions of osteoporosis.Osteoporosis is one of the most common chronic diseases,and the number of patients having this health problem concomitantly increasing as the population is aging.In 2006,it is estimated to affect 200 million women worldwide and cause more than 8.9 million fractures annually.Due to the rise in the aging population worldwide,the incidence of osteoporosis and related fracture is expected to increase substantially.The morbidity,mortality,and costs of medication for osteoporosis have been well recognized in women than in men.The mortality rate associated with osteoporosis is high,with approximately 65,000 deaths due to complications of osteoporotic fractures occurring annually.In addition to the financial burden,osteoporosis results in reduced functional independence and quality of life.The prevalence of osteoporosis increases with age and is higher in women than in men,with an overall incidence of 2-8% and 9-38%,respectively,in men and women of developed nations.As many as 1 in 2 women vs 1 in 4 men older than 50 years will incur an osteoporosis-related fracture in their lifetime.Osteoporosis is most prevalent in aging women over the age of 50 years as the hormonal protective influence of sex steroids such as estrogens on bone health dissipates with the onset of menopause.Similarly,another study suggested that osteoporosis is three times more common in women than in men.Therefore,the prevalence of osteoporosis is expected to increase as a reason for the increasing aging population.The distribution of osteoporosis was varied across different populations.In 2010,more than ten million adults were estimated to have osteoporosis in the USA.Among Europeans,the rate of osteoporosis was reported to be 27.6 million in 2010.Of these,the results from Sweden suggest that 6.3% of men and 21.2% of women aged 50 to 80 were classified as osteoporotic with a twofold higher prevalence of osteoporosis in men(16.6%)and women(47.2%)aged 80 to 84 years old.In developing countries,osteoporosis will be of increasing importance due to increases in life expectancy.Osteoporotic fractures are defined as fractures associated with low bone mineral density(BMD)and they can cause substantial pain and severe disability and often lead to a reduced quality of life.These devastating problems have the challenge to treat due to some reasons.First,the nature of osteoporotic bone itself decreased density and its increased brittleness tends to fracture into more and smaller individual fragments creating more complex fractures than healthy bone.Second,osteoporotic fractures occur in elderly people who have decreased capacity to manage functional limitations,which leads to an increased risk of falling.Fractures occur mostly in the spine(vertebrae),hip(proximal femur),and wrist(distal radius).Among different types of osteoporotic fracture,hip fracture is a common and serious problem among the elderly,which is recognized as the cause of substantial cost,as well as a higher risk of disability,comorbidities,and mortality than any other fractures.Annually,the rates of hip fractures were up to 400 per 100,000 individuals per year and considerably higher fracture risk in women.The lifetime prevalence of a hip fracture is 20% for women and 10% for men,which is geographically varied.In the USA,age-adjusted hip fracture rates among women ?65 years of age of different ethnicity are highest in white women and lowest in black women.In general,studies indicated that the incidence of hip fracture in Asia is generally lower than in the United States.The consequences of hip fractures are associated with increased mortality;12% to 17% of patients with a hip fracture die within the first year,and the long-term increased risk of death is two-fold.Due to the average age of the world's population is increasing at an unprecedented rate,and this increase is changing the world.This explosion will affect the world and will lead to a greater number of individuals with osteoporosis and an increasing number of fractures.By 2050,the worldwide incidence of hip fracture is projected to increase by 240% in women and 310% in men.The epidemiologic projections estimate that the estimated number of hip fractures worldwide will rise from 1.66 million in 1990 to 6.26 million in 2050,even if ageadjusted incidence rates remain stable.Osteoporotic fracture imposes a considerable burden on health services due to high prevalence and reduced mobility,increased requirements for hospitalization,nursing home care,and increased risk of mortality.The average risk that a person older than 50 years will experience osteoporotic fracture has been estimated at 40% to 50% for women and 13% to 22% for men.In 2000,9 million osteoporotic fractures occurred worldwide,including 1.6 million hip fractures,1.7 million forearm fractures,and 1.4 million clinical vertebral fractures.The incidence of osteoporotic fractures varies widely among countries and is primarily related to differences in the population and utilization of public healthcare services.The rate for minimal trauma fractures in men and women aged 40 years and over was 198.2 per 100,000 persons between 2007 and 2008 in the Australian population.In a population-based study performed in England and Wales,the fracture rate during the follow-up period was approximately 991 and 1,065 per 100,000 person-years for men and women,respectively.Much higher rates were observed in Minnesota,U.S.,where the age-adjusted incidence of any fracture was 2,251/100,000 person-years in men and 3,155/100,000 person-years in women.The risk of hip fractures is the most serious because they almost always result in hospitalization and lead to death for approximately 20% and permanent disability for approximately 50%.Due to an increasingly aging population;by 2050,the worldwide incidence of hip fracture in men is projected to increase by 240% in women and 310% in men.The epidemiologic projections estimate that the estimated number of hip fractures worldwide will rise from 1.66 million in 1990 to 6.26 million in 2050,even if age-adjusted incidence rates remain stable.Across Europe,the age-standardized incidence of morphometric vertebral fracture is estimated at 10.7/1,000 person-years in women and 5.7/1,000 person-years in men.A much lower rate of vertebral fracture was found in the U.S.,where the age-adjusted rate was 1.45/1,000 person-years in women and 0.73/1,000 person-years in men.The age-specific prevalence of vertebral fracture in Asian countries is comparable to Western countries.There are several risk factors for osteoporotic fracture in society.These risk factors were categorized mainly into two groups: modifiable and non-modifiable risk factors.Non-modifiable risk factors,also known as fixed markers,are unchangeable risk factors that are useful for the identification of individuals with a high risk of fracture(e.g.advancing age,being Caucasians,being female,etc.).Modifiable risk factors,also called causal risk factors,are manipulative risk factors that increase the risk of osteoporotic fracture.Those factors can be used to predict the risk of fracture and to prevent its occurrence.The modifiable risk factor includes an adequate nutrient intake such as carotenoid,calcium,protein,smoking,alcohol use,low body weight or BMD,and Vitamin D.Carotenoids are a diverse group of multi-functional lipophilic pigments.They are especially important in plants as a component of photosynthetic systems,but also in human nutrition as biological antioxidants and as precursors of vitamin A.Therefore,an adequate intake of nutrients is a non-pharmacological intervention and prevention strategy for reducing the loss of bone quality or incidence of fracture,which is a modifiable risk factor.Though,adequate nutrition is an important modifiable factor influencing bone health.Carotenoids exist in abundance in fruit and vegetables,and their serum levels elevate with increasing fruit and vegetable intake.Dietary antioxidant carotenoid,which is enriched in vegetables and fruits,has been testified to protect the human body's defense against the reactive oxygen species.Recent studies in vitro and in vivo have shown that reactive oxygen species and free radicals are involved in osteoclastogenesis,in apoptosis of osteoblasts and osteocytes,and,therefore,in bone resorption.Also,fruit and vegetables are rich sources of nutrients for bone metabolisms that may influence bone health,such as flavonoids.Studies have consistently shown that higher fruit and vegetable intake has positive effects on bone mineral status,by the regulation of bone metabolism,it is mentioned due to antioxidant properties.The reactive oxygen may be involved in the bone resorptive process and that fruit and vegetable-specific antioxidants,such as carotenoids,are capable of decreasing this oxidative stress.Recently,an inverse relationship between carotenoid intake and lycopene with biochemical markers of bone turnover has been reported.The Framingham Osteoporosis Study reported a protective effect of carotenoids against 4-yr loss in trochanter bone mineral density in men and the lumbar spine in women.Similarly,studies in Europe suggested that a higher dietary intake of carotenoids improves bone mineral density and reduces osteoporotic fracture risk.Recent studies in vitro and in vivo have shown that reactive oxygen species and free radicals are involved in osteoclastogenesis,in apoptosis of osteoblasts and osteocytes,and,therefore,in bone resorption.Over 600 carotenoids have been reported with only over 50 detected in food and humans,the most predominant being ?-carotene,?-carotene,?-cryptoxanthin,lutein,zeaxanthin,and lycopene,which account for approximately 70% of all carotenoids.Some epidemiological studies inconsistently reported regarding individual carotenoid intake with bone mineral density and risk of osteoporotic fracture.Some of them were found favorable evidence of associations between dietary carotenoid intakes with a low incidence of fractures,but not all.Alpha-carotene is one of the carotenoids frequently present in food,also as provitamin A activity.Like another carotenoid,it has antioxidant and possibly anticarcinogenic properties,and may enhance immune function as well.From the source of alpha-carotene,72% of ?-carotene was provided by yellow-orange vegetables.Recent studies found that dietary total and individual carotenoids such as ?-carotene were inversely associated with hip fracture risk only in men.However,the Framingham Osteoporosis Study suggested that participants will developed a lower risk for hip fracture or non-vertebral fracture if they were in the highest tertile of total carotenoid or lycopene intake,respectively,but no associations were evident for ?-carotene dietary.Fruit and vegetables are the major sources of beta-carotene antioxidants,which have bone health properties.Thus,antioxidants are protective agents that inactivate reactive oxygen species and therefore significantly delay or prevent oxidative damage.In addition,important micronutrients and antioxidants are abundant in fruit and vegetables,including Mg,K,and vitamin C,it has a role in bone remodeling and helps to reduce age-related osteoporotic bone deterioration and risk of fracture.Moreover,antioxidant ?-carotene contributes to a body's defense against reactive oxygen species and reduces the development of several chronic diseases including osteoporosis and osteoporotic fracture.There is a positive association between dietary beta-carotene and bone mineral density.Studies suggested that higher dietary betacarotene is associated with a lower risk of hip fracture in middle-aged and elderly Chinese.On the other side,?-carotene antioxidant seems a reactive oxygen species that enhance osteoclastogenesis and reduce osteoblast apoptosis by stabilizing the ?-catenin signaling pathway;this may lead to bone resorption.Lycopene is a natural pigment synthesized by plants and microorganisms,but by animals' products.Among the major carotenoids in humans,lycopene ranks highest in singlet oxygen quenching ability twice as high as that of ?-carotene and 10 times higher than that of ?-tocopherol.It is the most predominant carotenoid in human plasma.It has been reported that dietary lycopene as well as its supplementation,could be a benefit against the development of numerous chronic diseases including cancer and heart diseases.At the cellular level,lycopene has been shown to inhibit the formation and resorption activity of osteoclasts and stimulate the growth and differentiation of osteoblasts.Sahni et al.suggested that higher lycopene intake(12,664 mg/d)was a protective effect against the risk of hip fracture.They also found that those consuming >4.4 servings/wk of lycopene had significantly fewer fractures.The findings through a randomized controlled trial in 60 postmenopausal women aged 50-60 years,in which a 4-month lycopene supplementation significantly reduced NTx concentration.Similarly,the Framingham Osteoporosis Study has suggested that subjects with higher lycopene intake had a decreased loss of BMD and a lower risk of hip fracture.Some studies reported that circulating lycopene concentrations were significantly lower in osteoporotic patients than in the controls.Lutein and zeaxanthin are two important carotenoids,which are naturally occurring carotenoids available in several different fruits,vegetables,legumes,the skin of seafood,and eggs.Lutein was sourced mainly from peas(16 %),with broccoli,cabbages,and other leafy vegetables providing approximately 10 % each;zeaxanthin was sourced mostly from citrus fruits(19 % from oranges),apples(>10 %),and green leafy and fruiting vegetables.Thus fruits and vegetables contribute the largest composition among the four subclasses of carotenoids.Some studies suggested that the null association between circulating lutein/zeaxanthin with bone mineral density(BMD),the occurrence of hip fracture or bone loss in the Framingham Osteoporosis Study.The results of our study are useful for making clinically relevant decisions about the dietary carotenoid intake on osteoporosis and its consequent fracture risk,especially can be beneficial for the aging population on how to reduce the risk of fracturePart ?: Association between carotenoid and bone mineral density: Data from NHANES 2013-2018Objective: We aimed to investigate the associations between dietary carotenoid intake and osteoporosis.And to provide a scientific basis of the correlation between dietary carotenoid intake and osteoporosis and important for public health strategies on the method of prevention and control.Methods: The results of this thesis were reported based on the data collected from the National Health and Nutrition Examination Survey(NHANES)2013-2018.The bone scans were administered to eligible survey participants 40 years and older.Bone mineral density was measured using dual-energy X-ray absorptiometry(DXA).According to world health organization,the criteria for diagnosing osteoporosis using bone mineral density measurements were categorized as normal(not more than 1.0 standard deviation below the young adult mean),osteopenia(between 1.0 and 2.5 SD below the young adult mean),osteoporosis(more than 2.5 SD below the young adult mean),and severe osteoporosis(more than 2.5 SD below the young adult mean with a fracture osteoporosis).Dietary carotenoid intake was the mean intake of each carotenoid nutrient ascertained from two consecutive 24-h dietary recalls.Participants with complete and valid data on alpha-carotene,beta-carotene,lycopene,and lutein+zeaxanthin,and femoral neck,total hip and lumbar spine bone mineral density were included in this analysis.Excluded participants due to incomplete and invalid data on alpha-carotene,beta-carotene,lycopene,and lutein+zeaxanthin,and femoral neck,total hip and lumbar spine bone mineral density,and anti-osteoporosis medication at bone mineral density test.The mean standard deviation for normal distribution,median(first quartile,third quartile)for non-normal distribution,and while categorical variables are presented as the frequency and percentage.Missing value treatment is required to be done on the data before it can be used for statistical analysis because missing values in the data can reduce the power of the model and can make us draw wrong inferences,which leads to wrong predictions and classifications.Therefore,we used generalized mean imputation methods to replace missing values in our study.In this study,a linear regression analysis was used to test the linear association between dietary carotenoid intake and bone mineral density.For the evaluation of model fit,we used the Akaike information criterion(AIC)and Bayesian information criterion(BIC),with the smallest value is the best fit of the model and best index indicators.The statistical significance of the correlation coefficient was tested by Fisher's r-to-z transformation method.All analyses were performed by using the R software and Statistical Analysis System(SAS).Results: 1.A total of 3533 participants were included in this analysis.Of this,1740 subjects were men,accounting for 49.25% of the total study population,and 1793 subjects were women,accounting for 50.75%.The average age of the participants was 62.13 years old.Over 75% of the study population was lied in the range of overweight with an average body mass index(BMI)greater than 25 kg/m~2.A 52.20% of the study population were suffered from hypertension.Out of the total population in this study,81.85% were alcohol users and 18.15% were non-users.The study population was mostly non-Hispanic white(1482 people)and followed by non-Hispanic black(838 people),accounting for 41.95% and 23.72% of the total study subjects respectively.2.The average intake of calcium,vitamin D were 0.86 mg/day/kcal and 4.50 mg/day/kcal respectively.The median duration of physical activity performed was 1.14 hours/day.Lycopene was the highest average dietary intake among individual carotenoids,which accounts for a median of 2.021 mg/day/kcal.The median dietary intakes of ?-carotene,?-carotene,and Lutein+zeaxanthin were 0.097,1.310,and 0.913 mg/day/kcal respectively.The average bone mineral density of the femoral neck,total hip,and lumbar spine of the subjects were 0.77,0.94,and 1.01 g/cm~2 respectively.3.The results of the multivariable linear regression model of the total hip bone mineral density show that advancing in age(?=-0.003,P<0.001),being a female(?=-0.136,P<0.001),BMI(?=0.009,P<0.001),non-Hispanic white race(?=-0.033,P<0.001)and non-Hispanic black race(?=0.025,P<0.001)had a significant effect on the total hip bone mineral density.In our analysis,advancing in age and being women had a high risk for low total hip bone mineral density(P<0.001).BMI and nonHispanic black race had a protective factor for the total hip bone mineral density(P<0.001).In multivariable linear regression analysis,prior history of hypertension,physical activities,and calcium intakes did not affect the total hip bone mineral density.Similarly,the non-Hispanic white race was negatively related to total hip bone mineral density.4.The results of the multivariable linear regression model show that advancing in age(?=-0.002,P<0.001),Being a female(?=-0.098,P<0.001),BMI(?=0.009,P<0.001),non-prior history of hypertension(?=-0.015,P=0.028),non-alcohol user(?=-0.009,P=0.039),non-Hispanic white(?=0.043,P<0.001)and non-Hispanic black race(?=0.085,P<0.001)were significantly associated with lumbar spine bone mineral density.The lumbar spine bone mineral density increases by 0.009 as one unit increases of BMI(?=0.009,P<0.001).Both non-Hispanic white and black races were positively associated with lumbar spine bone mineral density;which is statistically significant(P<0.001).5.The results of correlation analysis show that dietary lycopene intake was positively correlated with femoral neck(r: 0.051;P=0.003)and total hip bone mineral density(r: 0.067;P<0.001).Similarly,dietary intakes of alpha-carotene(r: 0.077;95% CI: 0.034,0.121)and beta-carotene(r: 0.058;95% CI: 0.015,0.102)were positively correlated with lumbar spine BMD.6.After adjusting for age,gender,BMI,alcohol use,prior history of hypertension,and race;a multivariable linear regression analysis was also performed on the relationship between dietary carotenoid intakes with femoral neck,total hip,and lumbar spine bone mineral density.The results show that there was a positive and linear relationship between lycopene intake with the femoral neck(?=0.001;P<0.001)and total hip bone mineral density(?=0.001;P<0.001).7.Dietary lutein+zeaxanthin intake was positively related to femoral neck bone mineral density(?=0.002;P=0.035).8.We compared the model fits of dietary carotenoid intake in the femoral neck,total hip,and lumbar spine BMD models.After adjusting for all covariates,the results of model comparison on the association between femoral neck BMD with alphacarotene(AIC=-3507.46,BIC=-3489.09),beta-carotene(AIC=-3505.84,BIC=-3487.47),lycopene(AIC=-3524.48,BIC=-3496.11),and lutein+zeaxanthin(AIC=-3508.36,BIC=-3489.97).Although,the results of model fit on the total hip BMD with alpha-carotene(AIC=-2868.35,BIC=-2849.98),beta-carotene(AIC=-2868.24,BIC=-2849.88),lycopene(AIC=-2882.90,BIC=-2864.53),and lutein+zeaxanthin(AIC=-2868.81,BIC=-2850.44).Similarly,the model fit comparison results on the association between lumbar spine with alpha-carotene(AIC=-1458.83,BIC=-1441.98),beta-carotene(AIC=-1453.59,BIC=-1436.74),lycopene(AIC=-1447.57,BIC=-1430.72),and lutein+zeaxanthin(AIC=-1446.67,BIC=-1429.82).The results of the Akaike information criterion(AIC=-3524.48)and Bayesian information criterion(BIC=-3496.11)show that dietary lycopene intake was the best indicator of the femoral neck and total hip bone mineral density.It is also the best index in the femoral neck and total hip bone mineral density model.Alpha-carotene intake was the best fit for the lumbar spine bone mineral density model.The results of the Akaike information criterion(AIC=-1453.59)and Bayesian information criterion(BIC=-1441.98)confirmed that dietary alpha-carotene intakes were the best indicator of lumbar spine bone mineral density.Conclusion: 1.Dietary lycopene intake was positively and linearly associated with femoral neck and total hip bone mineral density.2.Lutein+zeaxanthin intake was positively related to femoral neck bone mineral density.3.The results of AIC and BIC confirmed that dietary lycopene intake was the best index in the femoral neck and total hip bone mineral density model.4.Dietary carotenoid intake which is enriched lycopene and lutein+zeaxanthin may have a beneficial effect in protecting the loss of bone mineral density and its consequents of fracture risk.Part ?: A cross-sectional study on carotenoid intake and fracture risk: The NHANES 2013-2018Objective:We aimed to investigate the potential relationship between carotenoid intakes and fracture risk.And to provides a scientific basis for a reasonable adequate dietary such as carotenoid on the reduction of fracture risk.This study may be important especially for elders on how to reduce the risk of fracture and its consequence of the deteriorating quality of life.Methods: The data of this study was compiled from the National Health and Nutrition Examination Survey(NHANES)2013-2018.Demographic and health history information was collected through extensive household interviews,and standardized physical examinations including anthropometric,blood pressure,laboratory measurements were conducted at mobile examination centers(MEC).Participants with complete and valid data on alpha-carotene,beta-carotene,lycopene,and lutein+zeaxanthin,and fracture were included in this analysis.Participants were excluded due to: younger than 40 years old,missing or invalid data on the alphacarotene,beta-carotene,lycopene,and lutein+zeaxanthin,and fracture data.Similarly,the incidence of fracture due to major trauma(e.g.car accidents,fall from leader),and use of anti-osteoporosis medication at bone mineral density test were excluded from this analysis.A propensity score was calculated to estimate the probability of prior fracture cases by logistic regression model based on age,sex,and body mass index(BMI)covariates.Propensity score similarity using a caliper width equal to 0.25 of standard deviation(SD)of the logit of the score,based on without replacement and nearestneighbor matching was used to match each prior fracture case with a non-prior fracture case in 1:4 ratio.In descriptive statistics,continuous variables are presented as the mean(standard deviation)for normal distribution or median(first quartile(Q1),third quartile(Q2))for non-normal distribution covariates,while categorical variables are presented as frequency.We used generalized mean imputation methods to replace missing values.The logistic regression model was used to test the association between dietary carotenoid intake and fracture risk in the unadjusted and adjusted models.We used the Akaike information criterion(AIC)and Bayesian information criterion(BIC)for evaluation of model fit,with the smallest value of AIC and BIC,which are the best fit of the model and the best index indicators for fracture risk outcomes.All analyses were performed by using the R and Statistical Analysis System(SAS).Results: 1.A total of 5491 participants aged 40 years and above from the NHANES 2013-2018 were included.After 1:4 propensity score matching,1140 subjects with prior fracture cases and 4351 subjects without prior fracture were analyzed.Of the total included subjects,2609 subjects were men,accounting for 47.51%,and 2881 subjects were women,accounting for 52.49% of the total study subject.The average age of the subjects was 55.62 years old.Over 75% of the study population was lied in the range of overweight with an average body mass index(BMI)greater than 25 kg/m~2.44.64% of the study population were suffered from hypertension.Out of the total population in this study,84.87% were alcohol users and 15.13% were non-users.The study population was mostly non-Hispanic white race(2177 people)and followed by nonHispanic black race(1317 people),accounting for 39.65% and 23.98% of the total study subjects respectively.2.In the descriptive analysis,dietary lycopene intake was the highest average among individual carotenoids,which accounts for a median of 2.170 mg/day/kcal.The median dietary intakes of alpha-carotene,beta-carotene,and Lutein + zeaxanthin were 0.085,1.210,0.041,and 0.885 mg/day/kcal respectively.The average intake of calcium in the study subject was 0.89 mg/day/kcal.The median dietary intake of vitamin D was 4.00 mg/day/kcal.Similarly,the median duration of physical activity performed per day was 1.67 hours/day.3.In the multivariable analysis of fracture risk and related factors,we included variables such as age,prior history of hypertension,alcohol use,and race.In this analysis;non-prior history of hypertension(OR: 0.864;95% CI: 0.746,0.998;P=0.045)was significantly reduced the risk of fracture.For a non-alcohol user,the odds ratio of fracture risk was 0.658(95% CI: 0.401,0.942)compared with the alcohol users.However,being non-Hispanic white race(OR: 1.635;95% CI: 1.289,2.089;P<0.001)was associated with a higher risk of fracture.4.The relationship between dietary individual carotenoid intake and the risk of fracture also had been determined using a multivariable logistic regression model.After adjusting for age,prior history of hypertension,alcohol use,and race,the results of this analysis show that dietary lycopene intake was significantly reduced the risk of fracture.An average of 2.17mg/day/kcal lycopene intake decreases the risk of fracture by 1.4%(OR: 0.986;95% CI: 0.975,0.997,P=0.016).Moreover,dietary intakes of alpha-carotene(OR: 0.989;95% CI: 0.907,1.094;P=0.990),beta-carotene(OR: 1.009;95% CI: 0.969,1.032;P=0.953),and lutein+zeaxanthin(OR: 0.983;95% CI: 0.952,1.012;P=0.263)were involved in protecting the risk of fracture,but not statistically significant.5.After adjusting for all covariates,the result of the Akaike information criterion and the Bayesian information criterion on the association between fracture risk with alpha-carotene(AIC=5613.23,BIC=5626.46),beta-carotene(AIC=5612.26,BIC=5625.48),lycopene(AIC=5606.24,BIC=5619.46),and lutein+zeaxanthin(AIC=5610.71,BIC=5623.94).The result of AIC(5606.24)and BIC(5619.46)show that dietary lycopene intake was the influential nutrient for the protection of fracture risk compared with the other carotenoid intake.Conclusion: 1.The results of this analysis revealed that dietary lycopene intake was decreased the risk of fracture by 1.4%.2.Alpha-carotene,beta-carotene,and lutein+zeaxanthin were involved in protecting the risk of fracture,but not statistically significant.3.The consumption of carotenoids may be protective against any fracture risk in the elderly.Part ?: Carotenoid intake and risk of fracture: a Bayesian meta-analysisObjective: To investigate the association between carotenoid intake and risk of the fracture using a Bayesian approach.Methods: We systematically searched Pub Med,EMBASE,and Cochrane library databases for relevant studies until December 2020.The medical subject heading(Me SH)used for the search were “Alpha-carotene” OR “Beta-carotene” OR “Lycopene” OR “Lutein+zeaxanthin” OR “ Lutein” OR “Zeaxanthin” OR “Carotenoids” OR “Vitamin A” OR “Carotene” AND “Bone fracture” OR “Fracture” OR “Osteoporosis”.We also performed a hand search based on reference lists from published articles.Studies included in this meta-analysis based on the following criteria:(1)written in the English language;(2)original human studies;(3)the exposure of interest as alphacarotene,beta-carotene,lycopene,or lutein+zeaxanthin;(4)the outcome was fracture;(5)studies provided risk estimates for fractures.Newcastle-Ottawa Scale(NOS)was used to evaluate the quality of the individual study,studies with six star-items or less were considered as low quality,while with seven star-items or more were considered as high quality.Both frequentist and Bayesian random-effects models were used to synthesize data from individual studies.In the Bayesian model,it is mandatory to specify prior distributions.Therefore,we used three different prior distributions for effect size in our model: Non-informative,skeptical,and enthusiastic prior distribution.Heterogeneity across studies was assessed using Cochran's Q-statistic test and inconsistency was quantified by I~2 statistic and publication bias was assessed using Egger's tests.All analyses were performed by the Win BUGS and R statistical software.Results: 1.A total of 10 studies with the participants' age was in the range of 25 to 90 years(average age: 59.8±10.2 years).NOS scores of the studies ranged from 5 to 9 stars and seven studies were scored 7 or more,which was considered as high-quality.2.Alpha-carotene intake was negatively associated with any fracture risk(Risk Ratio(RR)0.92,95% Cr I: 0.71 to 0.99),but not for hip fracture risk(RR: 1.04;95% CI: 0.67,1.50).The posterior probability that alpha-carotene intake reduces the risk of any fracture by at least 0% was 81%.Non-significant heterogeneity was found for any fracture risk(P=0.51,I~2=0.0%)and hip fracture(P=0.56,I~2=0.0%)across included studies.3.Dietary beta-carotene intake was associated with a 32% decrease in the risk of fracture(RR: 0.68;95% credible interval(Cr I)0.53,0.85)among high(vs low)intake under the skeptical prior distribution analysis.The posterior probability that ?-carotene intake reduces the risk of any fracture by at least 20% was 95%.4.In sub-group analysis by design analysis,we found that dietary beta-carotene has a protective impact on the risk of fracture in both case-control studies(RR: 0.55;95% Cr I: 0.14,0.96)and cohort studies(RR: 0.82;95% Cr I: 0.58,0.99).The posterior probability that ?-carotene intake reduces the risk of any fracture by at least 10% was 77% and 92% in cohort studies and case-control studies respectively.5.By geographic region,the pooled RR of fracture risk... |
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