Lead in bone

Studies in rats have shown effects of lead on bone mineralization and bone growth. The effects observed in rats may be relevant to our understanding of the mechanisms for the growth deficits that have been associated with low-level in utero and childhood lead exposures. Additional studies of the effects of lead on bone metabolism in humans and in animal models would improve our understanding of the toxicological significance of lead in bone. 

Aufderheide AC, Wittmers LE Jr. 1992. Selected aspects of the spatial distribution of lead in bone. Neurotoxicol. 13 809-820. 

Chettle DR, Scott MC, Somervaille LJ. 1991. Lead in bone Sampling and quantitation using K X-rays excited by 109Cd. Environ Health Pespect 91 45-55. 

Erkkila J, Armstrong R, Riihimaki V, et al. 1992. In vivo measurements of lead in bone at four anatomical sites long term occupational and consequent endogenous exposure. Br J Ind Med 49 631-644. 

Hu H, Pepper L, Goldman R. 1991. Effect of repeated occupational exposure to lead, cessation of exposure, and chelation on levels of lead in bone. Am J Ind Med 20 723-735. 

Nilsson U, Attewell R, Christoffersson JO, et al. 1991. Kinetics of lead in bone and blood after end of occupational exposure. Pharmacol Toxicol 69 477-484. 

Pounds JG, Long GJ, Rosen JF. 1991. Cellular and molecular toxicity of lead in bone. Environ Health Perspect 91 17-32. 

Silbergeld EK. 1991. Lead in bone Implications for toxicology during pregnancy and lactation. Environ Health Perspect 91 63-70. 

Witimers LE Jr, Aufdcrheide AC, Wallgren J, et al. 1998. Lead in bone IV. Distribution of lead in the human skeleton. Arch Environ Health 43 381-391. 

Impalas (Aepyceros melampus) found dead in Kruger National Park, South Africa, had elevated concentrations of copper in livers (maximum 444 mg/kg FW) and kidneys (maximum 141 mg/kg FW) authors assert that copper poisoning is the most likely cause of death (Gummow et al. 1991), but this needs verification. Copper concentrations in bones, kidneys, and livers of white-tailed deer (Odocoileus virginianus) near a copper smelter and from distant sites are about the same. However, deer near the smelter have significantly elevated concentrations of cadmium in kidneys and livers, lead in bone, and zinc in kidneys (Storm et al. 1994). 

In the cladoceran Daphnia magna, about 90% of the total body lead burden is adsorbed to the exoskeleton (Berglind et al. 1985). In animals with a vertebral column, total amounts of lead tend to increase with age. By far the most lead is bound to the skeleton, especially in areas of active bone formation (Barth et al. 1973 Tsuchiya 1979 USEPA 1980 Hejtmancik et al. 1982 Mykkanen etal. 1982 Peter and Strunc 1983 De Michele 1984 Eisler 1984 Berglind etal. 1985 Marcus 1985). The retention of lead stored in bone pools poses a number of difficulties for the usual multicompartmental loss-rate models. Some lead in bones of high medullary content, such as the... 

The selectivity (or specificity ratio) is useful for defining the magnitude of an analytical interference for real situations. Photon ratios serve only to demonstrate the demands upon the spectrometer. The selectivity ratio is the concentration of interfer-ent that causes a unit concentration error in the analyte. If the selectivity ratio of 2000 (defined as adequate by industry)(41) is used, the apparent lead concentration in the bone ash will be 250 ppm. A calcium/lead selectivity ratio of 5,000,000 is required to achieve an analytical accuracy of 10 per cent for one ppm lead in bone ash. (The authors are aware of a lead analysis for bone ash containing approximately 30 ppm lead that was reported by an ICP laboratory to contain approximately 550 ppm lead.) In this instance the selectivity ratio was only 1 x 103. 

After absorption, lead enters the blood, and 97% is taken up by red blood cells. Here, lead has a half-life of two to three weeks during which there is some redistribution to the liver and kidney, then excretion into bile or deposition in bone. After an initial, reversible, uptake into bone, lead in bone becomes incorporated into the hydroxyapatite crystalline structure. Because of this, past exposure to lead is possible to quantitate using X-ray analysis. It is also possible to detect lead exposure and possible poisoning from urine and blood analysis, and the amount in blood represents current exposure. However, as lead is taken up into the red blood cell, both the free blood lead level and that in the erythrocytes needs to be known. 

When appropriately validated and understood, biomarkers present unique advantages as tools for exposure assessment (Gundert-Remy et al, 2003). Biomarkers provide indices of absorbed dose that account for all routes and integrate over a variety of sources of exposure (IPCS, 1993, 2001a). Certain biomarkers can be used to represent past exposure (e.g. lead in bone), recent exposure (e.g. arsenic in urine), and even future target tissue doses (e.g. pesticides in adipose tissue). Once absorbed dose is determined using biomarkers, the line has been crossed between external exposure and the dose metrics that reflect the pharmacokinetics and toxicokinetics of an agent (see section 5.3.3). 

Fortunately, many metal ions are less harmful than they might be because of their intrinsic chemical behavior, such as formation of insoluble compounds in the gut with subsequent elimination of the metal ion. Other fractions of metal ions travel in the blood to other tissues, where they are immobilized, like lead in bone, or to the liver or kidneys, where they are complexed in a less toxic or disposable form. Even a... 

Silbergeld, E.K., J. Sauk, M. Somerman, A. Todd, F. MeNeil, B. Fowler, A. Fontaine, and J. van Buren. 1993. Lead in bone Storage site, exposure source, and target organ. NeuroToxicol. 14 225-236. 

Since lead in bone has a biologic half-life measmed in decades, compared to a biologic half-life of lead in blood of only 2-4 weeks [72], the bone more closely reflects cumulative body lead stores. Chelatable lead correlates well with bone lead [4, 31]. The decrease in bone lead stores can be monitored by in vivo tibial K x-... 

Lead forms a more stable chelate and releases the calcium, which is then free to replace the lead in bones. 

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