Changes in blood and urinary cadmium levels and bone mineral density according to osteoporosis medication in individuals with an increased cadmium body burden

Abstract

The aim of this study was to assess changes in bone mineral density (BMD) and cadmium (Cd) levels in blood and urine in individuals living in a Cd-contaminated area according to the type of osteoporosis medication over a three-year period. This follow-up study included 204 residents living in the vicinity of a closed copper refinery, who had been found to have elevated urinary or blood Cd levels. Cd levels in the blood and urine, as well as BMD, were measured every 6 months. After the first BMD measurement, individuals were prescribed antiresorptives such as alendronate or vitamin D and calcium, according to their BMD. Subjects were classified according to the type of medicine provided over the previous 6 months. General linear models controlling for other factors were used to evaluate the effects of each type of medication on the participants' Cd levels and BMD. Spinal BMD showed a significant increase in the antiresorptive group compared to the nontreatment group. Significant decreases in blood Cd levels were found in the vitamin D and calcium group, in comparison to the nontreatment group, as well as a marginally significant decrease in the antiresorptive group. The vitamin D and calcium group showed a significantly greater decrease in urinary Cd levels than the nontreatment group. In contrast, antiresorptive medication was found to have a negative effect on urinary Cd excretion. These results suggest that vitamin D and calcium treatment for osteoporosis lowers blood Cd levels more effectively and improves urinary Cd excretion.

Vitamin D3 and calcium cosupplementation alleviates cadmium hepatotoxicity in the rat: Enhanced antioxidative and anti‐inflammatory actions by remodeling cellular calcium pathways

“…Previous reports have disclosed that Ca 2+ and VD 3 supplementations antagonized Cd-intestinal absorption and/or enhanced its excretion by the kidney. [31][32][33] Our study revealed that systemic, but not hepatic tissue, Cd levels were substantially lower in both monotherapy groups compared with the PC group, suggesting that the single protocols might have enhanced the renal excretion, whereas they had minimal effect on Cd-intestinal absorption. On the other hand, the VDC group disclosed the utmost corrective effects on serum and hepatic tissues Cd and Ca 2+ levels compared with the PC, VD, and Ca groups.…”

“…[30] However, none of the prior studies measured the hepatic expression of VD-related molecules with Cd toxicity despite the major roles of the liver in VD homeostasis. [25][26][27][28]32] This study, to the best of our knowledge, is the first to reveal that chronic Cd toxicity in the PC group was associated with marked inhibitions in hepatic VDsynthesizing enzymes and VDR alongside increases in the Cyp24a1 enzyme and VDBP. In addition, circulatory 25-OH VD was significantly declined in the PC group and correlated inversely with blood and hepatic Cd levels, liver enzymes, and the levels of prooxidant and proinflammatory markers.…”

“…Moreover, the relative mRNA and protein expressions (mean ± SD) of the CAM and CAMKIIA (panels A and B) and S100A1 and S100B (panels D and E) in liver tissue lysates from the different groups as well as their protein expressions by Western blot (panels C and F features of itai-itai disease, the most severe form of chronic Cd toxicity. [25][26][27][28]32] Low abnormal serum VD levels, [25][26][27][28]32] reduced the production of active VD 3 subsequent to the deactivation of renal Cyp27b1 hydroxylase [25,26] as well as increased VDBP loss in urine [48] have been documented with Cd toxicity. Interestingly, another in vitro study has also exposed that Cd disrupted active VD 3 cellular actions by mimicking the hormone at its VDR binding sites.…”

“…[35,45] The trafficking of Cd across intestinal and renal cellular barriers also coincided with inhibitions of several VDdependent Ca 2+ -transporting proteins and it was suggested that Cd promoted its gathering by causing enterocytes absorption hindrance and excessive renal excretion of Ca 2+ . [31][32][33] Moreover, VD 3 controls many cellular Ca 2+ -regulatory molecules including VDCCs, SOCs, and CAM-CAMKII. [50][51][52] VD 3 is also a potent anti-inflammatory and antioxidative hormone that has been shown to efficiently modulate many of the oxidative stress and the inflammatory pathways involved in Cd-induced cell damage.…”

“…[28,29] Cd also deterred the activities of the Cyp27b1 enzyme [25,26] and VDR, [30] thus inhibiting the actions of VD 3 . While Ca 2+ and VD 3 replenishments inhibited Cd-intestinal uptake and enhanced its renal excretion, [31][32][33] higher Ca 2+ intake also counteracted Cd-induced oxidative stress and inflammation. [34,35] However, none of the previous studies either measured the effects of Cd on the hepatic expression of VD-regulatory molecules or explored the protective antioxidative and anti-inflammatory actions of the hormone.…”