Increasing environmental pollution in modern society has given rise to concern about the accumulation of heavy metals in humans. Major heavy metals that threaten health include lead (Pb), cadmium (Cd), and mercury (Hg). The main route of exposure to these metals is ingestion; however, in an urban environment, atmospheric particulate originating from automobile exhaust and industries may make a significant contribution. The toxic effects of heavy metals on humans have been known for centuries. More specifically, acute Pb poisoning can result in headache, unstable emotion, abdominal pain, and various symptoms related to the nerves, and chronic exposure to lead further develops renal tubule damages [1]. It has been reported that elevation of blood Cd level, by increasing systolic blood pressure as well as diastolic blood pressure, increases the risk of hypertension [2]. One of the major poisonings by heavy metals is Minamata disease by Hg. It is caused by an excess ingestion of fishes that have accumulated Hg biologically [3].

Osteoporosis is a major public health problem in Korea. Heavy metals are proposed risk factors of osteoporosis, while adequate nutrient intake is necessary to prevent it. Especially, Pb is transported by blood to the soft tissues, where it remains for short periods and is finally deposited in bone. More than 90% of the Pb present in the body is stored in bones, where it may remain for decades [4]. It has been also reported that bone mineral density (BMD) is related with previous renal dysfunction caused by Cd exposure [5]. However, still the association among heavy metals, dietary factors, and BMD has never been assessed.

Adequate nutrition is an essential factor for bone health and for preventing heavy metal poisoning as well. It has been reported that poor nutrition status impairs the defense system against exposure to heavy metals, eventually causing heavy metal poisoning [6]. On the other hand, calcium (Ca) is an essential nutrient for bone density, and Ca also competes with Pb for binding and transport sites [7,8], so Ca intake may affect the level of Pb absorption. Therefore, it is needed to investigate the relationship between food and nutrient intake status and heavy metal exposure status with different BMD status.

The purpose of this study was to investigate the association among heavy metal exposure, nutrient intake status, and BMD by comparing heavy metals in serum according to status of BMD (in normal, osteopenic, and osteoporotic subjects) and to elucidate their relation with intakes of food and nutrients.

The present study examined the serum heavy metal status and its relation with intake of nutrients and food in osteopenia and osteoporosis subjects. Overall, we found little evidence of the association between serum heavy metal levels and BMD status in Korean adults, while we did observe negative relationships between serum heavy metal levels and intakes of certain food groups.

Among the various heavy metals, Cd has been reported to have association with low bone mass of the forearm [9-12] at considerably lower exposure levels. Also, a previous large population study has addressed this issue and reported a modestly increasing risk of osteoporosis at the total hip with increasing urinary Cd in women [13]. Cd is a widespread food contaminant, with cereals, vegetables, root vegetables, and potatoes being the major contributors (80%) to dietary Cd intake [14]. Experimental data demonstrate a direct effect of Cd on bone with decreased bone formation and increased bone resorption at Cd concentrations relevant to human exposures [15]. Cd-exposed osteoblast-like cells decreased their bone-forming activity and secreted prostaglandin E2 (PGE2), which, in turn, can increase the formation and activity of osteoclasts. In a study of bone marrow cells, Cd both accelerated the differentiation and enhanced the activity of new osteoclasts. In our study, the serum level of Cd was significantly higher in the osteoporosis group compared with the other two groups (p < 0.05). As shown in the general characteristics of this study, the average age of the osteoporosis group was significantly higher than that of the other groups. Age is a critical risk factor for osteoporosis as it develops slowly over a lifetime. Also heavy metals, after being absorbed and bound to tissues, are not easily excreted from the body, and their accumulation is increased by age due to their long half-life [16]. Therefore, age might affect both BMD and serum heavy metal levels. To investigate an association between heavy metal status and BMD without age effect, we carried ANCOVA-test controlling for age. After controlling for age, there was no significant difference in serum Cd level among the three groups.

A previous study supports associations between Pb and bone formation, as growth plate chondrocyte expression works via changes in alkaline phosphatase, collagen, proteoglycan and thymidine levels, leading to inhibited bone formation [17]. Based on a study of Berglund et al. [8], effects on BMD by Pb and Cd may occur via increased bone turnover either through their direct action on the kidney, which may increase renal tubular Ca resorption, or through bone resorption from increased parathyroid hormone and a decrease in active vitamin D. We did not find a significant difference of the serum Pb levels among the three groups with different BMD in our study. However, we did not analyze the bone metabolism makers, so further study is need to investigate the relationship bone metabolism and heavy metal exposure in Koreans.

Hg toxicity can be caused by an excess ingestion of fish that have accumulated Hg biologically. Hg is released into the atmosphere via industrial emissions. Elemental Hg is transformed to methyl Hg by bacteria in water and methyl Hg subsequently concentrates in fish. Therefore, the primary source of Hg exposure in the population is fish consumption [18]. In our study, a significant difference was not found in serum Hg level among the three groups; however, osteoporotic subjects consumed significantly higher amounts of fish and shellfishes than normal and osteopenic subjects. It is not hard to conclude that fish consumption may have a negative effect on BMD as they contain Pb. One study reported that blood Hg (mean level 4.5 µg/L) was associated with decreased osteoporosis risk evaluated in Korean women [19]. These results could be driven by the fact that the primary source of Hg in Korea was fish consumption [20]. Fish consumption provides essential n-3 and n-6 fatty acids [21], which are protective against osteoporosis [22]. Therefore, further studies are needed to investigate the complex association between BMD and fish consumption, as well as Hg contamination.

The heavy metal concentrations in the blood mainly reflect recent exposure, but are also influenced by the body burden, particularly after a long exposure [23]. Potential uncertainties with heavy metal exposure being based on blood heavy metal levels, the bioavailability and gastrointestinal absorption may vary depending on dietary factors such as fiber content and nutritional status. Plant food generally contains a higher concentration of Cd than meat, dairy, and fish. Among plant foods, the highest concentrations are generally present in cereals such as wheat and rice, leafy green vegetables, and potatoes and root vegetables [24-26]. From the previous studies, cereals and vegetables contribute to about 80% of dietary Cd exposure. However, in our study, serum Cd levels had a significant and negative correlation with cereal intake. There are some possible explanations for this discordance. First, food Cd concentrations differ according to the different soles and environment. Second, we could consider the main type of cereals which the subjects have consumed. According the Korea Nutrition and Health Examination Survey [27], the main food for cereals is rice, which contains high soluble fibers. It is well known that animal protein containing sulfuric amino acids has detoxifying properties [28]. This is also partially supported by our study results showing a negative correlation (p = 0.0529) between serum Pb level and daily intake of animal protein.

Heavy metal exposure can impair Ca absorption, displacing Ca with metals and decreasing bone mineralization [15,16]. If it is restated, Ca intake may affect the level of heavy metals absorption. In our study, the intake of milks, one of the best Ca source showed a significant and negative correlation with serum Cd level. Also, there was a negative correlation between Ca intake and serum levels of Pb and Cd without significance.

Our study has several limitations. Firstly, cross-sectional design makes it difficult to determine causality. Even after some adjustments were made, potential confounding factors may have remained. Secondly, the study had a small sample size and thus needs to be repeated using a larger population. Thirdly, we just measured metals in serum given that serum levels reflect exposure on the order of several months. Urinary levels of metals or hair levels of Hg or bone Pb would have provided a longer-term biomarker of exposure.

In conclusion, we did not find a direct association between serum heavy metal levels and BMD status in some Korean adults. However, negative relationships were found between serum heavy metal levels and intake of some foods (cereals, milks, and total food). Further follow-up studies must be conducted to identify the relation between BMD and heavy metals in large samples with different BMD status.