Because bone accounts for > 94% of the adult body burden of Pb (70% in children) (O’Flaherty 1995
), many researchers accept that a cumulative measure of Pb dose may be the most important determinant of some forms of toxicity (cumulative measure means an exposure that is integrated over many years, rather than based on a single BPb measurement) (Landrigan and Todd 1994
; Hu et al. 1998
). In support of this hypothesis, recent studies have shown that bone-Pb but not BPb is significantly related to declines in hematocrit and hemoglobin among moderately Pb-exposed construction workers and to decreased birth weight and increased odds of clinically relevant hypertension (Gonzalez-Cossio et al. 1997
; Hu et al. 1996
). According to Hu et al. (1998)
, other adverse health outcomes likely to be associated with bone-Pb levels include impairment of cognitive performance and growth in children and kidney failure, gout, elevated blood pressure, reproductive toxicity, and adverse cardiovascular events in adults.
As pointed by Hu et al. (1998)
, two major paradigms relate to skeletal Pb: bone-Pb as an indicator of cumulative Pb exposure (bone-Pb as a repository), and bone-Pb as a source of body burden that can mobilized into the circulation (bone-Pb as a source). Hernandez-Avila et al. (1998)
reported a strong association between bone-Pb levels and serum-Pb levels of adults exposed to Pb. That study indicated the potential role of the skeleton as an important source of endogenous, labile Pb that may not be adequately discerned through measurement of BPb levels. The same authors argued that skeletal sources of Pb accumulated from past exposures should be considered along with current sources when exposure pathways are being evaluated. In an attempt to characterize the source of Pb exposure, Gulson et al. (1995)
measured the 206
Pb isotopic ratios in immigrant Australian subjects, Australian-born subjects, and environmental samples. The immigrant population exhibited Pb isotopic ratios from 17.7 to 18.5, distinct from the ratio in Australian-born subjects (~ 17.0). This difference allowed a distinction to be drawn between current exposure acquired from Australian sources and older bone-stored Pb that was not acquired from Australian sources.
Differing bone types have differing bone-Pb mobilization characteristics. For example, the tibia principally consists of cortical bone, whereas the patella is largely trabecular bone. Pb in trabecular bone is more biologically active than Pb in cortical bone, and trabecular bone has a shorter turnover time. The endogenous contribution of Pb from bone stores is an important health consideration. The O’Flaherty kinetic model can be used to indicate the quantity of Pb delivered from bone as a function of bone turnover and Pb exchange (O’Flaherty 1995
). A recent revision of this model (Fleming et al. 1999
) suggests that a smeltery worker with a tibia Pb concentration of 100 μg/g can expect a continuous endogenous contribution to BPb of 16 μg/dL. A pregnant woman with a tibia Pb concentration of 50 μg/g can end up with a contribution of 8 μg/dL BPb; this figure does not consider the increased rate of bone turnover associated with pregnancy. Individuals not exposed to Pb in the workplace typically display tibia Pb levels up to about 20 μg/g (Roy et al. 1997
Over the last decade bone-Pb measurements based on noninvasive in vivo
X-ray fluorescence (XRF) methods have become increasingly accepted. The technique uses fluorescing photons to remove an inner-shell electron from a Pb atom, leaving it in an excited state. The result is emission of X-ray photons that are characteristic of Pb. Measurements are performed by using one of four kinds of XRF: two involve fluorescence of the K-shell electrons of Pb (K-XRF), and the other two involve fluorescence of the L-shell electrons (L-XRF) (Todd et al. 2002a
). Several groups, mainly in North America, have reported the development of in vivo
measurement systems; the majority have adopted the K-XRF approach based on excitation with a 109
Cd isotope and backscatter geometry because of its advantages: it provides a robust measurement with a better detection limit and a lower effective (radiation) dose (as compared to L-XRF) (Todd and Chettle 1994
). The radiation dose is not a limiting factor in using this technique with humans, as demonstrated by Todd and Chettle (1994)
Calibration is usually performed with Pb-doped plaster-of-Paris phantoms (Todd et al. 2002a
). Method accuracy has been evaluated through comparison of XRF data from cadaver specimens with electrothermal atomic absorption spectrophotometry data (Todd et al. 2002b
). However, XRF sensitivity and precision for Pb still constitute an analytical challenge. In addition to sample-to-sample reproducibility, XRF can also display a certain amount of imprecision associated with each calculated bone-Pb value (Ambrose et al. 2000
). This uncertainty, estimated using a goodness-of-fit statistic from the curve fitting of the background, ranged from 3 to 30 μg/g Pb; clearly, this represents a problem for measurements of low-level Pb namely, young children and nonexposed populations. Another problem inherent to the XRF technique is photon scattering due to overlying tissue or subject movement during the measurement period (Ambrose et al. 2000
). Normalization of the Pb signal to the calcium backscatter signal appears to solve this problem. Precision depends on the amount of tissue overlying the bone: the greater the thickness of tissue, the poorer the precision. Todd and Chettle (1994)
, comparing the K-shell with L-shell precisions with 3 and 6 mm of overlying soft tissue, reported that K-XRF precision worsens by only 5%, whereas L-XRF precision worsens by 49% for greater thickness. The precision of the L-XRF method is much more severely affected by the strong attenuation of the Pb L-shell X rays.
Todd et al. (2001)
reported contiguous inhomogeneities in the distribution of Pb toward the proximal and distal ends of the tibia bones. They speculated that the region of lower Pb concentration has lower blood flow in the Haversian canals and, consequently, less Pb available for uptake into bone matrix during bone remodeling (Todd et al. 2001
). Trabecular bone has a larger surface area and a greater volume of blood delivered per unit of time compared to cortical bone. In addition there are more active osteons per gram in trabecular bone to accomplish resorption and deposition. Hernandez-Avila et al. (1998)
reported that, in individuals with no history to occupational Pb exposure, bone-Pb (in particular trabecular Pb) exerts an additional independent influence on plasma-Pb after control for BPb.
Thus, an appropriate selection of the precise bone type to be analyzed for Pb content must be made before commencing. Moreover, further research on the relationship between various bone-Pb subcompartments and other Pb measures is warranted.