About 95% of the body's burden of lead (Pb) resides in bone. The availability of this Pb to target soft tissue organs is disputed. Diseases such as osteoporosis and renal osteodystrophy may mobilize Pb from bone to cause additional injury to soft tissues. chelation of Pb with CaNa2EDTA is thought to remove Pb from blood, soft tissues and some recently active bone. Reequilibration of bone Pb into soft tissues after chelation and the small amounts of total body Pb removed by chelation suggest that only a small amount of this potential reservoir in bone is available for chelation. However, a few case studies suggest that a considerable fraction of the Pb in blood is due to normal equilibration with bone indicating that exposure to Pb (as measured by blood Pb) may be as much endogenous as exogenous. We wish to examine the extent of this contribution of Pb from bone and test the hypothesis that storage of environmental Pb burdens in bone can be altered experimentally. To demonstrate the contribution of bone Pb to the total chelated Pb and to augment the amounts of Pb removed from bone, we propose to use a form of parathyroid hormone (PTH 1-34 amino acid fragment) as an adjunct to chelation with CaNa2EDTA. Workers with past exposure to Pb (mostly retired) will be used as subjects since the reservoir of Pb in bone is greater in such subjects. Subjects will be chelated first with CaNa2EDTA. After blood Pb concentrations (BPb) return to pre-chelation levels (allowing for reequilibration to steady state), subjects will be treated for five days with subcutaneous PTH (300 IU/d) and then chelated again with CaNa2EDTA. The main outcome is whether chelated amounts of Pb will be greater after bone turnover is increased with PTH. In the treatment of osteoporosis with bone building therapeutic regimens, one technique has been successful, that of activating osteoclasts/blasts with parathyroid hormone (PTH), or etidronate, depressing osteoclasts with calcitonin and allowing free uptake of supplemental calcium. We will measure blood Pb during this therapy to determine if altering the blood Pb/bonePb equilibrium in this way can result in lowered blood Pb. Preliminary studies have revealed a 25% decrease in blood Pb concentrations. Postmenopausal osteoporotic women will receive repeating cycles of this therapy for one year and control postmenopausal osteoporotic women will receive calcium supplementation only. Blood Pb will be measured at entry, at three weeks and at one year. The amount of bone Pb contributing to blood Pb has been estimated indirectly and variably from 28 to 70%, with air and dietary sources contributing the remainder. Bone Pb is likely to have a different isotopic composition than recently acquired environmental Pb present in the soft tissues. In a third study, blood, soft tissue, trabecular and cortical bone specimens will be obtained from deceased accident victims through the tissue transplant service at UCSF. Isotopic composition of Pb in these samples will be compared. We have demonstrated that isotopic ratios of Pb can be determined with high precision by thermoionization-mass spectrometry and that minor differences in isotopic composition can be easily detected. These measurements together with the determination of Pb isotopes in regional air and water, will allow us to calculate the contribution of bone Pb equilibrated into blood Pb.
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