| BackgroundCadmium is a metal with an atomic weight of 112.41.Cadmium is a natural element in the earth’s crust.The major industrial applications of cadmium include the production of alloys,pigments,and batteries.Cadmium has negative impacts on human health.Intoxication with cadmium in people usually occurs by inhalation of cigarette smoke,but it is also possible via food,water and air.For non-occupationally-exposed populations,diet is the primary source of Cd exposure.Cadmium exerts toxic effects on the kidneys,bone,liver,lungs,cardiovascular system,immune system and reproductive system.The kidney is the principal organ targeted by chronic exposure to cadmium.Although cadmium accumulates in bone,the bone disease that results from excessive cadmium exposure is believed to be secondary to changes in calcium metabolism due to cadmium-induced renal damage.Recent studies have found that Cadmium even at relatively low doses may be a risk factor for osteoporosis.Several trace elements such as calcium,magnesium,zinc and copper are essential for normal development of the skeleton in humans and animals.However,exact involvements of the trace elements in osteoporosis have not yet been fully clarified.In a public health context,to assess the long-term effect of Cd on the body and bone health of local residents in high-exposure areas is of great importance.Objective1 Long-term cadmium exposure and the association with bone mineral density.2 Involvements of the trace elements in osteoporosis induced by cadmium.Methods1 Epidemiological survey1.1 SubjectsThe chronic high-exposure group was represented by a random sample of residents in an area located in southern China.Samples of rice,which was the staple food in everyday meals,obtained from this area were found not to meet the food quality standard for Cd.A Cd-non-polluted rural area was selected to represent a group with low exposure.This group had many common features(socio-economic status,dietary habits and lifestyles)with the high-exposure group,but there was a much lower Cd level in rice.No Cd soil pollution had ever been reported in this area.1.2 QuestionnaireWe collected detailed information on residence,ages,occupation,medical history,diet and smoking status from each participant.1.3 ExaminationThe height,weight and medical consultation will be conducted by practitioner.The aim of medical consultation was to know the subjects’ medical history,most importantly,to know whether they carried the diseases that affected their renal function and bone health,which could further exclude those subjects whose abnormal renal function and osteoporosis were caused by other heavy metals.1.4 Detection of bone mineral densityThe Dual Energy X-ray Absorptiometry(DEXA)bone densitometer EXA-3000(Korea OsteoSys)would be used to detect the the distal radius bone mineral density(BMD)of subjects’ left arms.1.5 Collection,transportation and storage of the urineThe urinary samples would be collected,transported and stored according to the instructions in "Technical Guidelines of Health Monitoring of Heavy Metal Pollution(Trial)" published by the former Ministry of Health.All subjects should fast for eight hours,and collected their morning urinary specimen(more than 20 ml)using disposable clean container the next morning.Urinary specimen would be promptly placed in refrigerated containers containing ice packs.Those urinary specimen would be transported to the laboratory within 2 hours.After arriving the laboratory,they would be packed into two tubes,one of which would be used to check the concentration of urinary creatinine,another of which would be kept at-20℃.2 Laboratory TestingWe drew the right amount of urinary samples with micro sampler and detected urinary creatinine content using Jaffe’s assay as well as the instructions of the instrument detection parameters.Inductively coupled plasma mass spectrometry(ICP-MS)was used to determine the concentrations of cadmium,magnesium.phosphorus,calcium,copper and zinc.Cadmium and mineral elements magnesium.phosphorus,calcium,copper,zinc were corrected by urinary creatinine,results were represented by μg/g creatinine.3 Statistical analysisEpiData 2.0 software was used for data entry in blinded-double double,and SPSS 20.0 software was used for data analysis.The analysis showed that urinary cadmium,magnesium,phosphorus,calcium,copper,zinc and the ratio of calcium/phosphorus,a skewed distribution,was expressed as P50(P25～P75).The Mann-Whitney test was used to evaluate the differences of the above variables between exposed group and control group.The χ2 test was used to compare the abnormal condition of urinary cadmium and BMD between the exposed group and the control group.BMD and urinary samples have log-normal distributions,which meant Pearson correlation analysis could be applied here as it fit the application condition of Pearson correlation.Multiple linear regression equation could be set up with urinary cadmium,sex,age as independent variables and five mineral elements as the dependent variable.Furthermore,stepwise multiple linear regression analysis could be set up with BMD as the dependent variable,urinary cadmium,magnesium.phosphorus,calcium,copper,zinc,gender,age,height and weight as the independent variable.The coefficient of determination R2 was used to judge the extent of fitted of regression equation.And P<0.05 was considered statistically significant.Results1 The demographic characteristics of the subjectsA total of 298 subjects were recruited,including 155 subjects in the exposed group and 143 subjects in the control group.The difference of sex ratio,age distribution,years of residence between two groups was insignificant.A total of 223 subjects had completed the health examination,including 83 subjects in the exposed group and 140 subjects in the control group.2 Cadmium body burden levels of the subjectsThe urinary cadmium level in exposed group that P50 was 5.45 μg/g·cr,(P25-P75)were 2.62-10.68 μg/g·cr of in total subjects,which were higher than 1.69μg/g·cr,1.22-2.36 μg/g·cr in the control group(Z=-10.49,P<0.001).The abnormal rate of urinary cadmium was 51.6%,which w as higher than 2.8%in control group(χ2=87.56,P<0.001).After stratified by gender,the urinary cadmium level in exposed group that P50 was 3.85μg/g·cr,(P25-P75)were 2.35-8.70μg/g·cr in male,which were higher than 1.63μg/g·cr,1.19-2.29 μg/g·cr in the control group(Z=-7.03,P<0.001),the abnormal rate of urinary cadmium in exposed group was 43.8%,which was higher than 1.5%in control group(χ2=34.72.P<0.001),the urinary cadmium level in exposed group that P50 was 7.21 μg/g·cr,(P25-P75)were 3.42-12.79μg/g·cr in female,which were higher than 1.84μg/g·cr,1.24-2.56μg/g·cr in control group(Z=7.99.P<0.001).the abnormal rate of urinary cadmium in exposed group was 60.0%.which was higher than 3.9%in control group(χ2=55.35,P<0.001).3 The osteoporosis status of the subjectsThe prevalence of osteoporosis in exposed group was 33.7%in total examination population,which was higher than 4.5%in control group(χ2=34.97.P<0.001).After stratified by gender,the prevalence of osteoporosis in exposed group was 21.4%in male,which was higher than 4.7%in control group(χ2=34.97,P<0.001).The prevalence of osteoporosis in exposed group was 46.3%in female.which was higher than 3.9%in the control group(χ2=34.97,P<0.001).4 Effect of cadmium exposure on body’s mineral metabolic balanceThe urinary calcium,copper,zinc level in exposed group that P50 were 173.80,20.55,520.23 μg/g·cr in total subjects,which were higher than 142.42,15.44,430.09μg/g·cr in control group.The urinary calcium,copper,zinc level in exposed group that P25-P75 were 114.40～251.70.14.95～28.44,390.25～647.15 μg/g·cr.which were higher than 96.87～179.11,12.26～20.98,309.85～568.78 μg/g·cr in control group(Z values were-4.33,-5.04.-3.47.P<0.001).The urinary calcium/phosphorus ratio in exposed group that P50 was 0.29,(P25-P75)were 0.19-0.44.which were higher than 0.20,0.13-0.27 in control group(Z=-5.91,P<0.001).According to the results of Pearson correlation analysis,urinary cadmium were positively correlated with calcium,copper,zinc in total population,and the correlation coefficients were 0.31.0.61.0.38,P values<0.05.According to the results of multiple regression analysis,the effect of environmentally long-term exposure to cadmium on balance of urine calcium,copper,zinc metabolism was larger,β’ values were 0.31.0.59 and 0.39(P<0.001).5 The correlation among body levels of cadmium,mineral element and BMDAccording to the results of Pearson correlation analysis.BMD were negatively correlated with urinary cadmium,calcium in total examination population,and the correlation coefficients were-0.18,-0.16,P values<0.05.After stratified by gender,there was no significant correlation between BMD and urinary cadmium in male.BMD were negatively correlated with ages,urinary cadmium,calcium in female,and the correlation coefficients were-0.22,-0.37,-0.26,P values<0.05.According to the results of multiple regression analysis,urinary magnesium,phosphorus,calcium,copper,zinc,sex,age,body weight,the impact of these eight factors on BMD levels were not statistically significant(P>0.05).only the level of urinary cadmium and height influence on he level of BMD.Final fitting regression equation for the mineral elements:lgBMD=-0.804-0.041(lg urinary cadmium)+0.003(height).R2=0.053,The R2 value in equation of urinary cadmium and height could be used to explain the impact of changes BMD of 5.3%.The results prompted that BMD was affected by environmental cadmium exposure levels,it as one of factors of osteoporosis.Conclusion1 The prevalence of osteoporosis might be increased in environmentally long-term exposure to cadmium,with the increase of urinary cadmium levels,the prevalence of osteoporosis was also increasing.2 The metabolic balance of osteoporosis-related mineral elements calcium,copper,zinc were affected in environmentally long-term exposure to cadmium.In addition to cadmium exposure,the calcium also played an important role on the forming process of osteoporosis. |
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