IN VIVO QUANTIFICATION OF HEAVY METALS IN BONE AND TOENAIL USING X-RAY FLUORESCENCE (XRF)
Creators: name: Zhang, Xinxin
Publisher: name: Purdue University Graduate School
Year: 2020
Subjects: Medical biochemistry and metabolomics not elsewhere classified

description: <b><i>Background and Objective:</i></b> Pb is a well-known toxic metal that can accumulate in bones over time and still threatening large populations nowadays, even those who are environmentally exposed to it. Strontium (Sr) is a metal directly related to bone health and has been used in the treatment of osteoporosis disease as a supplement. Manganese (Mn) is an essential nutrient in the body, yet excessive Mn is toxic and affecting many organ systems. Another toxic metal, mercury (Hg), has been poising different populations primarily through seafood consumptions, especially inducing neurological disorders in infants and fetuses. Even though significant associations between the above metal exposures and health outcomes have been recognized over the decades, the current technologies are limited in assessing cumulative long-term exposures <i>in vivo</i> to evaluate such associations further. Bone and toenail are appropriate biomarkers to reflect long-term exposure due to the longer half-life of these metals in them than in the traditional biomarkers. Therefore, this work evaluated the usefulness of portable x-ray fluorescence (XRF) technology on <i>in vivo</i> quantification of Pb and Sr in bone, and Mn and Hg in toenail. <b><i>Materials and Methods:</i></b> The portable XRF device was calibrated by using the Pb- and Sr-doped bone-equivalent phantoms, and Mn- and Hg-doped nail-equivalent phantoms, correspondingly in different projects. Seventy-six adults (38-95 years of age, 63 ± 11 years) from Indiana, USA, were recruited to participate in this study. For the <i>in vivo</i> bone measurements, each participant was measured at the mid-tibia bone using the portable XRF and K-shell XRF system (KXRF). We estimated the correlation between the bone Pb concentration measured by both devices to evaluate the use of the portable XRF in the bones. Using the portable XRF, the bone Sr exposure of the study population were simultaneously assessed with the bone Pb exposures. Besides, we analyzed the mid-tibia bone Sr data of a Chinese population, which were measured with the same portable XRF device by our research group. We also examined the extent to which the detection limit (DL) of the portable XRF was influenced by scan time and overlying soft tissue thickness for both Pb and Sr. For the exposure assessment of Mn and Hg in toenails, we first established system calibrations and determined the DL with phantoms. In order to validate the portable XRF in a population study, the recruited participants were measured at the big toenail by the device, and their toenail clippings were analyzed by the inductively coupled plasma spectrometry (ICP-MS). Besides, we analyzed the toenail data of an occupationally-exposed population, collected by our collaborators in Boston. A portable XRF device with the same model as ours was used in that study. <b><i>Results:</i></b> The uncertainty of <i>in vivo</i> individual bone measurement increased with higher soft tissue thickness overlying bone, and reduced with extending measurement time. With thickness ranging from 2 to 6 mm, the uncertainty of a 3-minute <i>in vivo</i> measurement ranged from 1.8 to 6.3 ug/g (ppm) for bone Pb and from 1.3 to 2.3 ppm for bone Sr. Bone Pb measurements via portable XRF and KXRF were highly correlated: R=0.48 for all participants, and R=0.73 among participants with soft tissue thickness &lt; 6 mm (72% of the sample). A trend of different bone Sr concentrations was observed across the races and sexes. The DL of the portable XRF with 3-minute toenail measurements was 3.59 ppm for Mn and 0.58 ppm for Hg. The portable XRF and ICP-MS measurements were highly correlated in the occupational populations for both Mn (R = 0.59) and Hg (R = 0.75). A positive correlation (R = 0.34) was found for toenail Mn measurements in the environmentally-exposed population, while a non-significant correlation was observed for toenail Hg due to the extremely low-level of Hg (Mean = 0.1 ppm) in the study population. <b><i>Discussion and Conclusion:</i></b> The portable XRF could be a valuable tool for non-invasive <i>in vivo</i> quantification of bone Pb and Sr, especially for people with thinner soft tissue; and of toenail Mn and Hg, especially for people with moderate- to high-level exposures.