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Brian Gulson,^1,2 Karen Mizon,^1,2 Howard Smith,³ John Eisman,⁴ Jacqueline Palmer,² Michael Korsch,² John Donnelly,⁵ and Kay Waite³

¹Graduate School of the Environment, Macquarie University, Sydney, New South Wales, Australia; ²CSIRO/EM, North Ryde, New South Wales, Australia; ³Department of Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia; ⁴Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; ⁵John B Donnelly & Associates Pty Limited, Sydney, New South Wales, Australia

Abstract

There has been renewed interest in impacts on physiologic systems in the middle and older age groups, especially from fractures and hypertension. Increased blood lead (BPb) levels in postmenopausal females, which are thought to arise from bone demineralization, may also relate to other health effects including hypertension. Taking advantage of natural differences in lead isotope signature between Australian sources of lead and those from other countries, a 2-year pilot study was performed in premenopausal and postmenopausal females and male partners in which the subjects were administered a bisphosphonate, alendronate, for 6 months. The aim of the study was to determine how lead isotopes and lead concentrations changed in relation to bone remodeling processes. Premenopausal subjects were a woman (and male partner) from Bosnia and two women from Colombia. The postmenopausal subject was a woman from Russia. Her male partner and one man from Sri Lanka were included. Multigenerational Australian subjects were 2 perimenopausal women and 1 postmenopausal woman. Each subject had blood and urine samples collected for markers of bone turnover and for lead isotope studies monthly for 7-9 months before, for 3 months during, and for up to 6 months after treatment with alendronate to inhibit bone resorption. Each subject thus acted as his or her own control. As predicted, there were significant decreases in the lead isotope ratio, ²⁰⁶Pb/²⁰⁴Pb, for the migrant subjects during treatment compared with the pretreatment period (p < 0.01) . After cessation of treatment, an increasing isotope ratio for the postmenopausal subject (and older male partner) occurred later than for premenopausal subjects, indicative of prolonged efficacy of the alendronate for the older subjects. The average BPb concentrations in migrant subjects decreased by about 20% during the treatment compared with the pretreatment period (p < 0.01) . To our knowledge, these are the first BPb concentrations reported over monthly to quarterly intervals for environmentally exposed adults over an extended period. The changes in lead isotopic composition and lead concentration are consistent with a decrease in bone resorption and associated mobilization of lead during alendronate therapy. Older subjects at risk of fractures may benefit from treatment with antiresorptive therapy, such as the potent bisphosphonates, with the added bonus of lower release of lead from bones and thus less risk of the potential adverse health effects of increased BPb levels. Key words: bisphosphonate, blood, bone mineral density, bone turnover, isotopes, lead, NTx test. Environ Health Perspect 110:1017-1023 (2002) . [Online 27 August 2002]

http://ehpnet1.niehs.nih.gov/docs/2002/110p1017-1023gulson/ abstract.html

Address correspondence to B.L. Gulson, Graduate School of the Environment, Macquarie University, Sydney, NSW 2109, Australia. Telephone: 61 2 9850 7983. Fax: 61 2 9850 7972. E-mail: bgulson@gse.mq.edu.au

We thank M. Salter for phlebotomy, and we thank the participants in this study.

Received 24 January 2002 ; accepted 14 March 2002.