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Bone as a possible target of chemical toxicity of natural uranium in drinking water.

Article Excerpt
Uranium accumulates in bone, affects bone metabolism in laboratory animals, and when ingested in drinking water increases urinary excretion of calcium and phosphate, important components in the bone structure. However, little is known about bone effects of ingested natural uranium in humans. We studied 146 men and 142 women 26-83 years of age who for an average of 13 years had used drinking water originating from wells drilled in bedrock, in areas with naturally high uranium content. Biochemical indicators of bone formation were serum osteocalcin and aminoterminal propeptide of type I procollagen, and a marker for bone resorption was serum type I collagen carboxy-terminal telopeptide (CTx). The primary measure of uranium exposure was uranium concentration in drinking water, with additional information on uranium intake and uranium concentration in urine. The data were analyzed separately for men and women with robust regression (which suppresses contributions of potential influential observations) models with adjustment for age, smoking, and estrogen use. The median uranium concentration in drinking water was 27 [micro]g/L (interquartile range, 6-116 [micro]g/L). The median of daily uranium intake was 36 [micro]g (7-207 [micro]g) and of cumulative intake 0.12 g (0.02-0.66 g). There was some suggestion that elevation of CTx (p = 0.05) as well as osteocalcin (p = 0.19) could be associated with increased uranium exposure (uranium in water and intakes) in men, but no similar relationship was found in women. Accordingly, bone may be a target of chemical toxicity of uranium in humans, and more detailed evaluation of bone effects of natural uranium is warranted. Key words: bone, bone turnover markers, CTx, drinking water, osteocalcin, P1NP, uranium. doi:10.1289/ehp.7475 available via http://dx.doi.org/[Online 30 September 2004]

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Increased uranium levels in groundwater are associated with uranium-rich ores and high solubility of uranium under oxidizing conditions in soft and bicarbonate-rich waters (Salonen 1994). Consequently, exceptionally high uranium concentrations have been found in private drilled wells located mostly in the southern part of Finland (Salonen and Huikuri 2002). We identified earlier a cohort of people who live in that area and use drilled wells for drinking water (Kurttio et al. 2002).

In long-term exposure, uranium accumulates in the bone and kidneys (Leggett and Pellmar 2003; Pellmar et al. 1999). The kidney has been considered the main target organ of chemical toxicity of uranium in humans, but effects in other tissues or organs remain poorly known. The intake of natural uranium through drinking water is associated with kidney function, particularly increased fractional excretion of calcium and phosphate in urine (Kurttio et al. 2002). The implications of the accumulation of natural uranium in the bone in humans are not known. The early distribution of uranium in the skeleton is similar to that of calcium (Leggett 1994). Uranium is assumed to deposit on the bone surface, and the uranyl ion (U[O.sub.2.sup.2+]) is assumed to be exchanged with calcium ions at the surf:aces of bone mineral crystals but not to participate in crystal formation (Leggett 1994). Gradually, uranium is redistributed in the bone and other tissues. The current biokinetic model of the International Commission on Radiological Protection suggests three compartments for uranium in human bone: bone surface, exchangeable bone volume, and nonexchangeable bone volume (Leggett 1994). It also suggests that uranium leaves bone surfaces more slowly than does calcium and that the removal from the nonexchangeable bone compartment may occur but with the rate of bone turnover.

The resemblance of uranium metabolism to that of calcium in bone enables the effects of uranium on bone. Indeed, uranium administration in rats is known to affect the bone. Acute (Guglielmotti et al. 1984) or continuous (Diaz Sylvester et al. 2002) exposure to uranium may lead to decreased bone formation rate and also increased bone resorption (Ubios et al. 1991) in rats.

The aim of this study was to assess whether uranium intake through drinking water affects the biochemical markers of bone turnover in humans. The present study extends our previous study, which suggested that uranium exposure is associated with altered proximal renal tubular function (Kurttio et al. 2002). To our knowledge, this is the first report on the possible effects of ingested natural uranium on bone in humans.

Materials and Methods

Study population. The source population was identified from the drinking water database of STUK-Radiation and Nuclear Safety Authority, with radionuclide analyses of more...