The current status of osteoporosis after 15 years of reduced cadmium exposure among residents living in cadmium-contaminated areas in northwestern Thailand.

The purposes of this study were to determine the prevalence of osteoporosis after 15 years of reduced cadmium exposure and to determine the association between urinary cadmium (U-Cd) and osteoporosis. The study was conducted with 937 participants (109 males, 828 females) living in a cadmium-contaminated area in northwestern Thailand. All participants were required to respond to a questionnaire. Bone mineral density (BMD) was investigated by measurements taken at the calcaneus by dual-energy X-ray absorptiometry. U-Cd, which reflects the amount of cadmium contained in the body, was measured by atomic absorption spectrophotometry (AAS). The geometric mean of U-Cd was significantly higher in males than in females (p < 0.001). The mean level of BMD for females was found to be statistically significantly lower than that for males (p < 0.001). Increasing U-Cd levels were correlated with decreasing levels of BMD. The association between U-Cd and osteoporosis appeared to exist only at concentrations of U-Cd ≥ 10 µg/g creatinine (OR = 2.7, 95% CI = 1.2-5.9). It can be concluded that despite discontinued or reduced cadmium exposure for more than 10 years, the effect of cadmium toxicity on bone, which is stronger in women, continues, as cadmium, once absorbed, will accumulate in the human body for a long time due to its extremely long half-life.

HUMAN HEALTH EFFECTS FROM CADMIUM EXPOSURE: COMPARISON BETWEEN PERSONS LIVING IN CADMIUM-CONTAMINATED AND NON-CONTAMINATED AREAS IN NORTHWESTERN THAILAND.

Environmental cadmium contamination is present in some rural villages of Mae Sot District, Tak Province, northwestern Thailand. We compared the health of 751 persons aged ≥ 35 years living in 3 contaminated villages with 682 people from 3 non-contaminated villages with similar socio-demographic and lifestyle characteristics in the same district. All the subjects were screened for urinary cadmium (a biomarker for long-term cadmium exposure), renal function, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, urinary tract stone disease and bone mineral density in 2012. The study renal functions included urinary excretion of ß2-microglobulin (early tubular effect), total urine protein and glomerular filtration rate (glomerular effects). The geometric mean of urinary cadmium level was significantly higher among persons living in the contaminated areas (2.96 µg/g creatinine) than those in the non-contaminated areas (0.60 µg/g creatinine). Persons living in contaminated areas had a significantly higher prevalence of renal dysfunction, bone mineral loss, hypertension and urinary stones than those living in non-contaminated areas. There were no significant differences between the 2 groups in the prevalence of diabetes, hypercholesterolemia and hypertriglyceridemia. This study shows health effects due to environmental cadmium exposure. The prevalences of diabetes, hypercholesterolemia, and hypertriglyceridemia were not associated with cadmium exposure.

Renal and blood pressure effects from environmental cadmium exposure in Thai children.

Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of ß2-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥ 1 µg/g creatinine. The prevalence of urinary cadmium ≥ 1 µg/g creatinine was significantly higher in girls and in those consuming rice grown in cadmium-contaminated areas. The geometric mean levels of urinary ß2-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary ß2-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children.

Progress in cadmium-related health effects in persons with high environmental exposure in northwestern Thailand: a five-year follow-up.

Food-borne cadmium was the principal source of exposure for persons living in the 12 cadmium-contaminated villages in Mae Sot District, Tak Province, northwestern Thailand. This report presents progress in cadmium-related health effects among persons with high cadmium exposure. The study included 436 persons who had urinary cadmium levels ≥5 µg/g creatinine and were screened for urinary cadmium, renal function, hypertension, diabetes and urinary stones in 2005 (baseline) and 2010 (5-year follow-up). Study renal biomarkers included urinary excretion of ß(2)-microglobulin (ß(2)-MG), total protein and calcium, serum creatinine and glomerular filtration rate (GFR). The geometric mean level of urinary cadmium statistically significantly reduced from 9.5±1.6 µg/g creatinine in 2005 to 8.8±1.6 µg/g creatinine in 2010. Compared to baseline, the follow-up examination revealed significant increases in urinary ß(2)-MG (tubular effect), urinary total protein and serum creatinine, and a decrease in GFR (glomerular effects). Progressive renal dysfunctions were similarly observed in persons both with and without reduction in cadmium intake. Significant increases in prevalence of hypertension, diabetes and urinary stones were also detected at follow-up. These three disorders were found to markedly impair renal functions in the study persons. Our study indicates that in persons with prolonged excessive cadmium exposure, toxic health effects may progress even after exposure reduction. Renal damage from cadmium can be due to its direct nephrotoxic effect and also through the related disorders causing nephropathy.

An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: a population study.

Excessive urinary calcium excretion is the major risk of urinary stone formation. Very few population studies have been performed to determine the relationship between environmental cadmium exposure and urinary stone disease. This population-based study examined an association between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and prevalence of urinary stones in persons aged 15 years and older, who lived in the 12 cadmium-contaminated villages in the Mae Sot District, Tak Province, northwestern Thailand. A total of 6748 persons were interviewed and screened for urinary cadmium and urinary stone disease in 2009. To test a correlation between urinary excretion of cadmium and calcium, we measured urinary calcium content in 1492 persons, who lived in 3 villages randomly selected from the 12 contaminated villages. The rate of urinary stones significantly increased from 4.3% among persons in the lowest quartile of urinary cadmium to 11.3% in the highest quartile. An increase in stone prevalence with increasing urinary cadmium levels was similarly observed in both genders. Multiple logistic regression analysis revealed a positive association between urinary cadmium levels and stone prevalence, after adjusting for other co-variables. The urinary calcium excretion significantly increased with increasing urinary cadmium levels in both genders, after adjusting for other co-variables. Elevated calciuria induced by cadmium might increase the risk of urinary stone formation in this environmentally exposed population.

Changes in cadmium exposure among persons living in cadmium-contaminated areas in northwestern Thailand: a five-year follow-up.

OBJECTIVE: To determine changes in cadmium exposure among persons aged 15 years and older who lived in the 12 cadmium-contaminated villages in northwestern Thailand. MATERIAL AND METHOD: Urinary cadmium was measured among villagers in 2004. An exposure reduction campaign was conducted soon afterwards, and in 2009, urinary cadmium was measured among people living in the same villages. The survey participants were asked about their smoking status and consumption of rice grown locally in cadmium-contaminated areas. Both were the two main routes of cadmium exposure in these villages. RESULTS: Seven thousand six hundred ninety seven and 6748 persons participated in the first and second surveys, respectively. The proportion of current smokers was higher in the first survey (34.9%) than the second survey (31.5%). The proportion of persons who consumed rice grown locally decreased from 88.0% in the first survey to 50.5% in the second survey. Of persons who consumed rice grown locally, the proportion of those with urinary cadmium > or =2 microg/g creatinine increased from 55.5% in the first survey to 61.3% in the second survey. Of persons consuming rice purchased from other areas, the proportion of those with urinary cadmium > or =2 microg/g creatinine decreased from 46.7% in the first survey to 35.6% in the second survey. In both surveys, the adjusted odds ratio for increasing prevalence of high urinary cadmium associated with consumption of locally grown rice was greater than that for tobacco smoking. CONCLUSION: Urinary excretion of cadmium significantly decreased after environmental cadmium exposure was reduced.

Lack of safety systems in agricultural settings in rural Thailand: a report of three worker death.

BACKGROUND: Three farm workers lost consciousness within a few minutes after entering a silo pit on a farm located in a rural Thai village. All victims died later in the hospital. OBJECTIVE: To identify the cause of unconsciousness in these victims and to determine safety systems for agricultural enterprises containing silos. MATERIAL AND METHOD: Medical records of the three decedents were reviewed for demographic characteristics, clinical manifestations, and the cause of deaths. Co-workers of the decedents were interviewed to obtain details of the victims' work on the farm during the incident. Concentrations of oxygen and other potentially hazardous gases were measured in the pit where the victims collapsed. All agricultural enterprises that have silos in the district were identified and investigated for safety systems. RESULTS: Of the three decedents, two died in a rescue attempt. They all developed metabolic acidosis and died 1-3 days following admission. Oxygen concentration at the top of the pit was 20.9% and decreased to 0.8% at a depth of 1 meter and to 0.0% at the bottom of the three-meter pit. Carbon dioxide, which is heavier than air, was the major asphyxiant displacing oxygen in this confined space. Lack of safety systems were detected on this farm and in all settings containing silos in the district. CONCLUSION: Asphyxiation due to oxygen depletion was the cause of all deaths. It is essential to install safety systems for work in confined spaces in agricultural settings.

Correlations of urinary cadmium with hypertension and diabetes in persons living in cadmium-contaminated villages in northwestern Thailand: A population study.

Risk for hypertension and diabetes has not been conclusively found to be a result of cadmium exposure. A population-based study was conducted in 2009 to examine the correlations of urinary cadmium, a good biomarker of long-term cadmium exposure, with hypertension and diabetes in persons aged 35 years and older who lived in the 12 cadmium-contaminated rural villages in northwestern Thailand. A total of 5273 persons were interviewed and screened for urinary cadmium, hypertension, and diabetes. The geometric mean level of urinary cadmium for women (2.4+/-2.3 microg/g creatinine) was significantly greater than that for men (2.0+/-2.2 microg/g creatinine). Hypertension was presented in 29.8% of the study population and diabetes was detected in 6.6%. The prevalence of hypertension significantly increased from 25.0% among persons in the lowest tertile of urinary cadmium to 35.0% in the highest tertile. In women, the rate of hypertension significantly increased with increasing urinary cadmium levels in both ever and never smokers, after adjusting for age, alcohol consumption, body mass index, and diabetes. In men, such association was less significantly found in never smokers. The study revealed no significant association between urinary cadmium and diabetes in either gender. Our study supports the hypothesis that environmental exposure to cadmium may increase the risk of hypertension. Risk for diabetes in relation to cadmium exposure remains uncertain in this exposed population.

Cadmium induced renal dysfunction among residents of rice farming area downstream from a zinc-mineralized belt in Thailand.

High levels of cadmium (Cd) in paddy soil and rice, and a concurrent increase in urinary Cd of inhabitants in the Mae Sot District, Tak Province, Thailand first emerged in 2003. Risk factors such as occupation, sources of staple food and drinking water as well as biomarkers of adverse renal effects of the increased body burden of Cd were investigated in 795 residents, 30 years or older, whose urinary Cd levels were between 0.02 and 106mug/g creatinine. Farmers who consumed their own rice and residents who sourced drinking water from wells and/or the river demonstrated increased urinary Cd. Age-adjusted mean urinary cadmium for male and female subjects who consumed well water was 5.7mug/g vs. 6.1mug/g creatinine while the corresponding value for male and female subjects who did not consume well water was 3.7mug/g vs. 4.8mug/g creatinine, respectively. Increased urinary levels of beta(2)-microglobulin and N-acetyl-beta-d-glucosaminidase were observed with the increase in urinary Cd, indicating tubular dysfunction and renal damage associated with increase in Cd body burden. Consumption of well water and rice grown in the contaminated area increase the body burden of Cd. Cessation of exposure is essential to prevent and possibly recover from Cd toxicity, especially among the residents whose kidney damage and malfunction may be reversible.

Cadmium-exposed population in Mae Sot district, Tak province: 3. Associations between urinary cadmium and renal dysfunction, hypertension, diabetes, and urinary stones.

OBJECTIVE: To study the associations between urinary cadmium and renal dysfunction, hypertension, diabetes, and urinary stones in an adult population living in cadmium-contaminated areas in Mae Sot District, Tak Province, Thailand. MATERIAL AND METHOD: Seven hundred ninety five cadmium-exposed adults were screened for urinary cadmium, renal dysfunction, hypertension, diabetes, and urinary stones in 2005. Six selected markers of renal function in the present study were urinary excretion of beta2-microglobulin (beta2-MG), N-acetyl-beta-D-glucosaminidase (NAG), total protein and calcium, serum creatinine, and glomerular filtration rate (GFR). RESULTS: The mean age of the study persons was 50-years-old. The overall prevalence rates of hypertension, diabetes, and urinary stones were 33.3%, 6.2%, and 8.9% respectively. The prevalence of increased proteinuria was greatest in those with urinary cadmium levels > or = 15 microg/g creatinine. Urinary excretion of beta2-MG, NAG, and total protein significantly increased with increasing urinary cadmium levels, after adjusting for other co-variables by multiple linear regression analysis. However, urinary cadmium was not significantly associated with urinary calcium, serum creatinine, and GFR. The prevalence rates of hypertension, diabetes, and urinary stones did not significantly increase with increasing urinary cadmium levels. Hypertension, diabetes, and urinary stones were also significant predictors of impaired renal function. CONCLUSION: In this population, increasing levels of urinary cadmium are associated with increasing urinary excretion of beta2-MG, NAG, and total protein. Risk for hypertension, diabetes, and urinary stones remains uncertain in relation to cadmium exposure.

Cadmium-exposed population in Mae Sot District, Tak Province: 4 bone mineral density in persons with high cadmium exposure.

OBJECTIVE: To measure bone mineral density in cadmium-exposed persons aged 40 years and older that lived in the 12 contaminated villages in northwestern Thailand. MATERIAL AND METHOD: Five hundred seventy three persons with urinary cadmium levels > or = 5 microg/g creatinine during the 2004-2006 surveys were screened in 2007 for urinary excretion of cadmium, bone formation and resorption markers, and renalfunction markers. Calcaneus bone density was measured in each person by a dual-energy X-ray absorptiometry bone scanner. RESULTS: The mean age of the study persons was 57 years old. The geometric mean level of urinary cadmium for women was significantly higher than that for men. Women had a lower mean of calcaneus bone density than men. The rate of osteoporosis in women (21.5%) was significantly higher than that for men (14.7%). Calcaneus bone density was negatively correlated with urinary excretion of calcium (in both genders) and crosslinked N-telopeptide of type I collagen (in women), after adjusting for other co-variables. Increasing urinary cadmium levels appeared to correlate with reduced bone density in women, but not in men. In both genders, urinary excretion of beta2-microglobulin and N-acetyl-beta-D-glucosaminidase was higher in persons with osteoporosis than those without. CONCLUSION: Bone mineral loss is correlated with urinary cadmium levels and renal dysfunction in this female population.

Cadmium-exposed population in Mae Sot District, Tak Province: 2. Prevalence of renal dysfunction in the adults.

BACKGROUND: In 2004, 7,697 cadmium-exposed persons aged 15 years and older in Mae Sot District, Tak Province, Thailand, were screened for urinary cadmium levels and 554 cases (7.2%) had > or = 5 microg/g creatinine. OBJECTIVE: The present study reported the prevalence of renal dysfunction among those with high urinary cadmium (> or = 5 microg/g creatinine). MATERIAL AND METHOD: The study persons were interviewed and examined for detection of renal dysfunction. Venous blood and second morning urine were obtained from each subject for microscopic analysis and biochemistry measurements. RESULTS: Of the 527 examined persons, 14.2% had urinary beta2-microglobulin excretion between 300 and 999 microg/g creatinine, and 19.9% contained > or = 1,000 microg/g creatinine. About 21.1% had serum creatinine concentrations between 1.1 and 1.4 mg/dl and 4.2% contained > or = 1.5 mg/dl. Low glomerular filtration rate (GFR < 60 ml/min/1.73 m2 body surface area) was present in 16.9% of the study persons. Of the persons surveyed, 75.3% had the fractional excretion of phosphate > 5% and 24.7% contained the fractional excretion of potassium > 10%. The overall prevalence rates of hypertension and urinary stones in the study population were 31.3% and 8.9%, respectively. Excretion of urinary beta2-microglobulin significantly increased with increasing urinary cadmium levels. Both increased serum creatinine and decreased GFR appeared to be associated with increasing urinary cadmium although the difference was not statistically significant. There were no significant associations between urinary cadmium levels and excretion of urinary protein, urinary calcium, hypertension, and urinary stones. CONCLUSION: Excessive exposure to cadmium might produce renal dysfunction among the present study population. Increased urinary excretion of beta2-microglobulin is a good indicator of renal tubular dysfunction among persons with excessive cadmium exposure.

Cadmium-exposed population in Mae Sot District, Tak Province: 1. Prevalence of high urinary cadmium levels in the adults.

BACKGROUND: In Mae Sot District, Tak Province, Thailand, the paddy fields receiving irrigation from the two creeks and crops grown in the areas were found to contain markedly elevated cadmium levels during the surveys in 2001-2004. OBJECTIVE: The present report carried out a survey in 2004 to determine urinary cadmium, a good index of excessive cadmium exposure and body burden, among the exposed residents aged 15 years and older in these contaminated areas. MATERIAL AND METHOD: Morning urine samples were collected from the subjects and then kept frozen until cadmium analysis. Urinary cadmium was determined using the atomic absorption spectrometry and urinary creatinine was determined using a method of reaction with picric acid at alkaline pH and colorimetry. RESULTS: Of the 7,697 persons surveyed, only 45.6% had urinary cadmium levels < 2 microg/g creatinine. About 4.9% were between 5 and 10 microg/g creatinine and 2.3% had cadmium concentrations > 10. The urinary cadmium level was greater among women than men and increased with increasing age. Smokers were more likely to have high urinary cadmium than non-smokers. Persons who mainly consumed rice grown locally in the contaminated areas had higher urinary cadmium than those who did not. CONCLUSION: Persons who had high urinary cadmium levels and might have cadmium-induced toxic effects should be screened for early detection of chronic cadmium toxicity. Smoking cessation programs should be one component of preventive action beneficial for the study population. The production of rice and other crops for human consumption should be prohibited to prevent further accumulation of cadmium in the body of the exposed population.