| Bone Lead as a Biological Marker in Epidemiologic Studies of Chronic Toxicity: Conceptual Paradigms Howard Hu,
1,2
Michael Rabinowitz,
3,4
and Donald Smith
5
1
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA
2
Occupational Health Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115 USA
3
Marine Biological Laboratory, Woods Hole, MA 02543 USA
4
Department of Neurology, Harvard Medical School, Boston, MA 02115 USA
5
Environmental Toxicology, University of California, Santa Cruz, CA 95064 USA Abstract
The skeleton contains the majority of the body's lead burden in both children and adults. The half-life of lead in bone is in the range of years to decades, depending on bone type, metabolic state, and subject age, among other things. Measurement of skeletal lead has benefited greatly from the recent development of X-ray fluorescence (XRF) instruments that can make rapid, safe, accurate, and relatively precise measurements of lead in bone. Two types of XRF technologies exist, LXRF and KXRF ; this paper focuses on KXRF, which has been the most widely validated and used. KXRF is proving to be a powerful analytical methodology for evaluating bone lead levels as a measure of time-integrated (i.e., cumulative) lead dose in epidemiologic studies of the effects of chronic lead exposure. However, insufficient attention has been given to conceptualizing the paradigms by which bone lead levels reflect lead exposure and by which the skeleton serves as an endogenous source of lead. Consideration of these paradigms, which rely on bone lead kinetics, is necessary for the proper development of a priori hypotheses involving bone lead accumulation and release, the selection of bone sites for measurement by KXRF, and the design of epidemiologic studies involving bone lead dynamics. We discuss and present supporting evidence for a conceptual model that distinguishes two major paradigms of skeletal lead, including 1) bone lead as an indicator of cumulative lead exposure (bone lead as repository) , and 2) bone lead as a source of body lead burden that is mobilizable into the circulation (bone lead as source) . These two roles are not mutually exclusive. Instead, they are components of the processes controlling lead accumulation into and release from bone over time. Developing successful strategies for distinguishing these two processes in epidemiologic studies will require separate measurements of lead in cortical and trabecular bone and additional measurement of specific markers of bone mineral turnover and resorption. It may also involve developing accurate methods for evaluating lead in labile compartments of the circulation, such as plasma, as a potentially useful and responsive measure of bone lead release, of the partitioning of circulatory lead, and of the toxicological significance of lead released from bone to other target organs. Key words : blood, bone, lead, osteoporosis, plasma, X-ray fluorescence. Environ Health Perspect 106:1-8 (1998) . [Online 2 January 1998]
http://ehpnet1.niehs.nih.gov/docs/1998/106p1-8hu/ abstract.html Address correspondence to H. Hu, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115 USA. Support for this research was provided by NIEHS ES 05257-01A1, NIEHS P42-ES05947, NIEHS Center grant 2 P30 ES 00002, NIEHS ES07535, and the UC MEXUS program. We are indebted to Joel Schwartz for his advice on lead kinetics, Susan Korrick for her advice on biological markers of bone resorption, Gail Fleischaker for help with computer graphics, Jaylyn Olivio for editorial assistance, and Darlene Bramble for secretarial assistance. Received 14 July 1997 ; accepted 26 September 1997.
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