Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms.
Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms.
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DOI：
10.1289/ehp.981061
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发表时间：
1998-01
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
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无论是儿童还是成人，骨骼中都含有人体大部分的铅。骨骼中铅的半衰期在几年到几十年之间，具体取决于骨骼类型、代谢状态和受试者年龄等。骨骼铅的测量极大地受益于最近发展的 X 射线荧光 (XRF) 仪器，这些仪器可以快速、安全、准确且相对精确地测量骨中的铅。存在两种类型的 XRF 技术：LXRF 和 KXRF；本文重点关注 KXRF，它已得到最广泛的验证和使用。事实证明，KXRF 是一种强大的分析方法，用于评估骨铅水平，作为慢性铅暴露影响的流行病学研究中时间积分（即累积）铅剂量的衡量标准。然而，对于骨铅水平反映铅暴露以及骨骼作为铅的内源源的概念化范式的关注还不够。考虑这些依赖于骨铅动力学的范式对于正确发展涉及骨铅积累和释放的先验假设、选择用于 KXRF 测量的骨部位以及设计涉及骨铅动力学的流行病学研究是必要的。我们讨论并提出了概念模型的支持证据，该模型区分了骨骼铅的两个主要范式，包括1）骨铅作为累积铅暴露的指标（骨铅作为储存库），2）骨铅作为可移动到循环中的身体铅负担的来源（骨铅作为来源）。这两个角色并不相互排斥。相反，它们是随着时间的推移控制铅在骨骼中积累和释放的过程的组成部分。在流行病学研究中制定成功区分这两个过程的策略将需要单独测量皮质骨和小梁骨中的铅，并额外测量骨矿物质更新和吸收的特定标志物。它还可能涉及开发准确的方法来评估循环中不稳定区室（例如血浆）中的铅，作为骨铅释放、循环铅的分配以及从骨释放到其他靶器官的铅的毒理学意义的潜在有用和响应性测量。
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.