Bone and kidney effects from cadmium exposure : dose effect and dose response relationships

Sammanfattning: Cadmium is a heavy metal that has been dispersed in the environment during the last century due to human activity. It is well known that high cadmium exposure causes renal damage and in severe cases also osteoporosis and osteomalacia. Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established, but little is known about the contribution of environmental risk factors. The aim of the present work was to investigate the effects of low cadmium exposure on bone and kidneys. A cross-sectional study was performed in 520 men and 544 women, aged 16-81, environmentally or occupationally exposed to cadmium. Cadmium in urine as well as in blood was used as the dose estimate, and protein HC was used as a marker of tubular proteinuria, an early sign of renal damage. Bone mineral density (BMD) in the forearm was measured using DXA (dual energy x-ray absorptiometry) technique. The study revealed that tubular proteinuria occurred in cadmium exposed persons at lower levels of cadmium doses than previously known. At levels between 0.3 and 0.5 nmol cadmium/mmol creatinine in urine, there was a two-fold increased risk of displaying elevated urinary protein HC, compared to the reference (<0.3). A dose-effect relationship was found between increasing cadmium dose and decreasing BMD for people aged 60 and older. In the older age group, there was a dose-response relationship, showing a three-fold increased risk of low BMD in the group with urinary cadmium higher than 3 nmol/mmol creatinine compared to the lowest dose group. The difference between the age groups may reflect that older bone is more sensitive to cadmium, or that it takes several decades for cadmium to affect bone. There was also evidence of an increased risk of forearm fractures with increasing cadmium levels. For the population aged 50 and over, the fracture hazard ratio increased by 18% per nmol cadmium/mmol creatinine. Renal tubular damage was negatively related to bone mineral density and increasing risk of forearm fractures, suggesting that the possible effect of cadmium on the bone may be an indirect effect mediated by the kidneys. Altogether the thesis reveals relationships between low cadmium doses and early kidney effects, decreased BMD and increased risk of forearm fractures. Although it is difficult to directly compare the cadmium levels in the present study with other groups having other exposure histories, the levels are in the same range as that of many people in the general population. Hereditary, endocrine and life-style factors are probably the primary causes of osteoporosis; however, a comparatively low increase in risk because of cadmium may have a large impact on public health, if a large part of the population has cadmium levels at which there is an increased risk.