The Effects Of Fluride And Cadmium On Bone

Fluorine(F) is widely distributing on the earth. It could be absorbed into human body by variable routes. It has been identified as possible trace elements by WHO and affects the metabolism of Calcium and Phosphate. In the past decades, fluorine is used to prevent and treat the decayed teeth. However, FLUORINE is thought as a kind of toxicant and induces fluorosis. The serious symptom of fluorosis is bone fluorosis. Cadmium(Cd) has been considered as a harmful pollutant of world wide concern. Bone was one target organ of cadmium and osteoporosis was the most familiar syndrome.The main presentation of bone fluorosis is osteoporosis. In China, X-ray is still the national diagnostic criterion for osteoporosis. But the X-ray implement is too huge to move. It was reported Cd affected bone through both direct and indirect ways such as impairing synthesizing of active vitamin D₃ in kidney. We used the removable single-photon absorptiometry(SPA) to measure the bone mineral density(BMD) of forearm radius in each subject of two study population exposed to fluorine and cadmium respectively. Urinary fluorine(UF),blood osteocalcin(Bone Gla Protein, BGP), blood alkaline phosphatase(AKP),blood bone specific alkaline phosphatase(BAKP), urinary Hydroxyproline(HYP) were also mensurated. Human peripheral blood lymphocytes(HPBLs) were separated to observe the core binding factor al(CBFAl) gene expression. In cadmium exposed population, Urinary cadmium(UCd), blood cadmium(BCd),total cadmium intake (TCd), urinary metallothonein(UMT) and biomarkers reflect renal dysfunction were also mensurated.It was showed that the value of BMD decreased significantly in exposure group as well as BGP and HYP. BGP significantly increased when UF was higher than 2mg/gCr,though HYP and BMD value were significantly different from control group when UF were higher than 4mg/gCr and 8mg/gCr respectively. After defined the abnormal value using the 90% upper limits of each index of control group, defined Z score <-2 as abnormal, we found the abnormal rates of Z score was significantly higher in exposure group of female. The decreased gene expression of CBFA1 and its increasing abnormal rate were observed in fluoride exposed group. We compared the benchmark dose value of UF for each index, BGP and CBFA1 had the smallest values.In Cd exposed population, BMD values of peoples were significantly related withUCd and BCd were higher than 10 μg/gCr and 20 μg/L respectively. The prevalence of osteoporosis(defined with T score<-2.5) was significantly increasing following the increase of UCd and BCd . UMT increased significantly if T score was abnormal. After benchmark dose calculation for T score, Z score, UMT and indice of renal dysfunction, we could find UNAG and UNAGB had the smallest values, T score, UALB and Z socre were ranged at last three positions.In addition, we obtained the osteoblasts from calvarias of newborn SD rat and treated with sodium fluoride(NaF) and cadmium chloride(CdCl₂) in order to understand their possible mechanisms on osteoblasts.In vitro experiments showed that NaF could stimulate osteoblastic proliferation and the activity of AKP at low dose levels and repress them at high dose levels. NaF could up-regulated the gene expression of ODF at all dose levels , up-regulated the gene expression of OPG when the doses were 0.5 and 1.0mmol/L. NaF could repress the gene expression of VDR, TGF- β and IGF-I at all dose levels , especially at high dose levels. Although CdCl₂ could decrease osteoblastic proliferation and the activity of AKP when the dose of CdCl₂ was higher than 0. 5μmol/L. CdCl₂ couldn't induce the expression of ODF while low level (0.01 0.05μmol/L) CdCl₂ could up-regulate gene expression of OPG and VDR. High level CdCl₂ (>0.5μmol/L) could repress the gene expression of OPG, VDR, TGF- β and IGF-I.In conclusion, exposure to fluorine could induce osteoporosis. Fluorine could induce bone mass losing by stimulating the bone formation and bone absorption without timely mineral deposition. Comparing the benchmark doses, the BGP in blood and CBFA1 gene expression of HPBLs were sensitive biomarkers while Z score was more specific. NaF at low level could promote osteoblasts' cytokines expression while high level NaF presented strong toxic characters.It has been demonstrated that high level of cadmium exposure could induce osteoporosis which occurs later than renal damage related to cadmium exposure. Comparing with indices reflect renal dysfunction, T score and Z score weren't sensitive adequately. UMT had a complicated relationship with bone effect of Cd. Low level Cd could stimulate some cytokines expression in osteoblast and when the level increased, Cd became more and more toxic.