In vivo X-ray fluorescence (XRF) measurement of bone lead concentratio
n (XRF) has emerged as an important technique for future epidemiologic
al studies of long-term toxicity. Several issues germane to epidemiolo
gic methodology need to be addressed, however. First, sources of varia
bility in measurements of bone lead need to be quantified, including i
mprecision related to the physical measurement itself and the variabil
ity of lead deposition over the two main compartments of bones (cortic
al vs. trabecular) and within each compartment Imprecision related to
the physical measurement can be estimated for each individual measurem
ent based on the variability of the signal and background. Second, app
roaches to low-level data need to be debated. We argue for using the m
inimal detection limit (MDL) to compare instruments and interpret indi
vidual measurements; however, with regard to epidemiologic studies, we
would abandon the MDL in favor of using all point estimates. in analy
ses using bone lead as an independent variable, statistical techniques
can be used to adjust regression estimates based on estimates of meas
urement uncertainty and bone lead variability. Third, factors that can
be expected to modify the relationship between bone lead and toxicity
such as gravida history, endocrinological states, nutrition, and othe
r important influences on bone metabolism, need to be identified and m
easured in epidemiologic studies. By addressing these issues, investig
ators will be able to maximize the utility of XRF measurements in envi
ronmental epidemiologic studies.