Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2002 Oct;110(10):1017–1023. doi: 10.1289/ehp.021101017

Skeletal lead release during bone resorption: effect of bisphosphonate treatment in a pilot study.

Brian Gulson 1, Karen Mizon 1, Howard Smith 1, John Eisman 1, Jacqueline Palmer 1, Michael Korsch 1, John Donnelly 1, Kay Waite 1
PMCID: PMC1241028  PMID: 12361927

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, (206)Pb/(204)Pb, 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.

Full Text

The Full Text of this article is available as a PDF (553.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baecklund M., Pedersen N. L., Björkman L., Vahter M. Variation in blood concentrations of cadmium and lead in the elderly. Environ Res. 1999 Apr;80(3):222–230. doi: 10.1006/enrs.1998.3895. [DOI] [PubMed] [Google Scholar]
  2. Blake K. C., Mann M. Effect of calcium and phosphorus on the gastrointestinal absorption of 203Pb in man. Environ Res. 1983 Feb;30(1):188–194. doi: 10.1016/0013-9351(83)90179-2. [DOI] [PubMed] [Google Scholar]
  3. Chesnut C. H., 3rd, Bell N. H., Clark G. S., Drinkwater B. L., English S. C., Johnson C. C., Jr, Notelovitz M., Rosen C., Cain D. F., Flessland K. A. Hormone replacement therapy in postmenopausal women: urinary N-telopeptide of type I collagen monitors therapeutic effect and predicts response of bone mineral density. Am J Med. 1997 Jan;102(1):29–37. doi: 10.1016/s0002-9343(96)00387-7. [DOI] [PubMed] [Google Scholar]
  4. Farias P., Borja-Aburto V. H., Rios C., Hertz-Picciotto I., Rojas-Lopez M., Chavez-Ayala R. Blood lead levels in pregnant women of high and low socioeconomic status in Mexico City. Environ Health Perspect. 1996 Oct;104(10):1070–1074. doi: 10.1289/ehp.961041070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Franklin C. A., Inskip M. J., Baccanale C. L., Edwards C. M., Manton W. I., Edwards E., O'flaherty E. J. Use of sequentially administered stable lead isotopes to investigate changes in blood lead during pregnancy in a nonhuman primate (Macaca fascicularis). Fundam Appl Toxicol. 1997 Oct;39(2):109–119. doi: 10.1006/faat.1997.2355. [DOI] [PubMed] [Google Scholar]
  6. Gulson B. L., Jameson C. W., Gillings B. R. Stable lead isotopes in teeth as indicators of past domicile--a potential new tool in forensic science? J Forensic Sci. 1997 Sep;42(5):787–791. [PubMed] [Google Scholar]
  7. Gulson B. L., Jameson C. W., Mahaffey K. R., Mizon K. J., Korsch M. J., Vimpani G. Pregnancy increases mobilization of lead from maternal skeleton. J Lab Clin Med. 1997 Jul;130(1):51–62. doi: 10.1016/s0022-2143(97)90058-5. [DOI] [PubMed] [Google Scholar]
  8. Gulson B. L., Mahaffey K. R., Jameson C. W., Mizon K. J., Korsch M. J., Cameron M. A., Eisman J. A. Mobilization of lead from the skeleton during the postnatal period is larger than during pregnancy. J Lab Clin Med. 1998 Apr;131(4):324–329. doi: 10.1016/s0022-2143(98)90182-2. [DOI] [PubMed] [Google Scholar]
  9. Gulson B. L., Mahaffey K. R., Mizon K. J., Korsch M. J., Cameron M. A., Vimpani G. Contribution of tissue lead to blood lead in adult female subjects based on stable lead isotope methods. J Lab Clin Med. 1995 Jun;125(6):703–712. [PubMed] [Google Scholar]
  10. Gulson B. L., Mahaffey K. R., Vidal M., Jameson C. W., Law A. J., Mizon K. J., Smith A. J., Korsch M. J. Dietary lead intakes for mother/child pairs and relevance to pharmacokinetic models. Environ Health Perspect. 1997 Dec;105(12):1334–1342. doi: 10.1289/ehp.971051334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gulson B. L., Mizon K. J., Palmer J. M., Korsch M. J., Taylor A. J. Contribution of lead from calcium supplements to blood lead. Environ Health Perspect. 2001 Mar;109(3):283–288. doi: 10.1289/ehp.01109283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Heaney R. P., Recker R. R., Stegman M. R., Moy A. J. Calcium absorption in women: relationships to calcium intake, estrogen status, and age. J Bone Miner Res. 1989 Aug;4(4):469–475. doi: 10.1002/jbmr.5650040404. [DOI] [PubMed] [Google Scholar]
  13. Heaney R. P. The bone-remodeling transient: implications for the interpretation of clinical studies of bone mass change. J Bone Miner Res. 1994 Oct;9(10):1515–1523. doi: 10.1002/jbmr.5650091003. [DOI] [PubMed] [Google Scholar]
  14. Heaney R. P., Yates A. J., Santora A. C., 2nd Bisphosphonate effects and the bone remodeling transient. J Bone Miner Res. 1997 Aug;12(8):1143–1151. doi: 10.1359/jbmr.1997.12.8.1143. [DOI] [PubMed] [Google Scholar]
  15. Hernandez-Avila M., Gonzalez-Cossio T., Palazuelos E., Romieu I., Aro A., Fishbein E., Peterson K. E., Hu H. Dietary and environmental determinants of blood and bone lead levels in lactating postpartum women living in Mexico City. Environ Health Perspect. 1996 Oct;104(10):1076–1082. doi: 10.1289/ehp.961041076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hernandez-Avila M., Villalpando C. G., Palazuelos E., Hu H., Villalpando M. E., Martinez D. R. Determinants of blood lead levels across the menopausal transition. Arch Environ Health. 2000 Sep-Oct;55(5):355–360. doi: 10.1080/00039890009604028. [DOI] [PubMed] [Google Scholar]
  17. Hu H., Aro A., Payton M., Korrick S., Sparrow D., Weiss S. T., Rotnitzky A. The relationship of bone and blood lead to hypertension. The Normative Aging Study. JAMA. 1996 Apr 17;275(15):1171–1176. [PubMed] [Google Scholar]
  18. Inskip M. J., Franklin C. A., Baccanale C. L., Manton W. I., O'Flaherty E. J., Edwards C. M., Blenkinsop J. B., Edwards E. B. Measurement of the flux of lead from bone to blood in a nonhuman primate (Macaca fascicularis) by sequential administration of stable lead isotopes. Fundam Appl Toxicol. 1996 Oct;33(2):235–245. doi: 10.1006/faat.1996.0161. [DOI] [PubMed] [Google Scholar]
  19. Kalkwarf H. J., Specker B. L., Bianchi D. C., Ranz J., Ho M. The effect of calcium supplementation on bone density during lactation and after weaning. N Engl J Med. 1997 Aug 21;337(8):523–528. doi: 10.1056/NEJM199708213370803. [DOI] [PubMed] [Google Scholar]
  20. Kim R., Landrigan C., Mossmann P., Sparrow D., Hu H. Age and secular trends in bone lead levels in middle-aged and elderly men: three-year longitudinal follow-up in the Normative Aging Study. Am J Epidemiol. 1997 Oct 1;146(7):586–591. doi: 10.1093/oxfordjournals.aje.a009318. [DOI] [PubMed] [Google Scholar]
  21. Kim R., Rotnitsky A., Sparrow D., Weiss S., Wager C., Hu H. A longitudinal study of low-level lead exposure and impairment of renal function. The Normative Aging Study. JAMA. 1996 Apr 17;275(15):1177–1181. [PubMed] [Google Scholar]
  22. Leggett R. W. An age-specific kinetic model of lead metabolism in humans. Environ Health Perspect. 1993 Dec;101(7):598–616. doi: 10.1289/ehp.93101598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Liberman U. A., Weiss S. R., Bröll J., Minne H. W., Quan H., Bell N. H., Rodriguez-Portales J., Downs R. W., Jr, Dequeker J., Favus M. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med. 1995 Nov 30;333(22):1437–1443. doi: 10.1056/NEJM199511303332201. [DOI] [PubMed] [Google Scholar]
  24. Manton W. I. Sources of lead in blood. Identification by stable isotopes. Arch Environ Health. 1977 Jul-Aug;32(4):149–159. doi: 10.1080/00039896.1977.10667273. [DOI] [PubMed] [Google Scholar]
  25. Manton W. I. Total contribution of airborne lead to blood lead. Br J Ind Med. 1985 Mar;42(3):168–172. doi: 10.1136/oem.42.3.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Muldoon S. B., Cauley J. A., Kuller L. H., Scott J., Rohay J. Lifestyle and sociodemographic factors as determinants of blood lead levels in elderly women. Am J Epidemiol. 1994 Mar 15;139(6):599–608. doi: 10.1093/oxfordjournals.aje.a117049. [DOI] [PubMed] [Google Scholar]
  27. O'Flaherty E. J. Physiologically based models for bone-seeking elements. IV. Kinetics of lead disposition in humans. Toxicol Appl Pharmacol. 1993 Jan;118(1):16–29. doi: 10.1006/taap.1993.1004. [DOI] [PubMed] [Google Scholar]
  28. Payton M., Riggs K. M., Spiro A., 3rd, Weiss S. T., Hu H. Relations of bone and blood lead to cognitive function: the VA Normative Aging Study. Neurotoxicol Teratol. 1998 Jan-Feb;20(1):19–27. doi: 10.1016/s0892-0362(97)00075-5. [DOI] [PubMed] [Google Scholar]
  29. Rabinowitz M. B. Toxicokinetics of bone lead. Environ Health Perspect. 1991 Feb;91:33–37. doi: 10.1289/ehp.919133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Reid D. M., Hughes R. A., Laan R. F., Sacco-Gibson N. A., Wenderoth D. H., Adami S., Eusebio R. A., Devogelaer J. P. Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study. J Bone Miner Res. 2000 Jun;15(6):1006–1013. doi: 10.1359/jbmr.2000.15.6.1006. [DOI] [PubMed] [Google Scholar]
  31. Schwartz B. S., Stewart W. F. Different associations of blood lead, meso 2,3-dimercaptosuccinic acid (DMSA)-chelatable lead, and tibial lead levels with blood pressure in 543 former organolead manufacturing workers. Arch Environ Health. 2000 Mar-Apr;55(2):85–92. doi: 10.1080/00039890009603392. [DOI] [PubMed] [Google Scholar]
  32. Silbergeld E. K., Schwartz J., Mahaffey K. Lead and osteoporosis: mobilization of lead from bone in postmenopausal women. Environ Res. 1988 Oct;47(1):79–94. doi: 10.1016/s0013-9351(88)80023-9. [DOI] [PubMed] [Google Scholar]
  33. Smith D. R., Osterloh J. D., Flegal A. R. Use of endogenous, stable lead isotopes to determine release of lead from the skeleton. Environ Health Perspect. 1996 Jan;104(1):60–66. doi: 10.1289/ehp.9610460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Staessen J. A., Bulpitt C. J., Fagard R., Lauwerys R. R., Roels H., Thijs L., Amery A. Hypertension caused by low-level lead exposure: myth or fact? J Cardiovasc Risk. 1994 Jun;1(1):87–97. [PubMed] [Google Scholar]
  35. Staessen J. A., Roels H., Fagard R. Lead exposure and conventional and ambulatory blood pressure: a prospective population study. PheeCad Investigators. JAMA. 1996 May 22;275(20):1563–1570. [PubMed] [Google Scholar]
  36. Symanski E., Hertz-Picciotto I. Blood lead levels in relation to menopause, smoking, and pregnancy history. Am J Epidemiol. 1995 Jun 1;141(11):1047–1058. doi: 10.1093/oxfordjournals.aje.a117369. [DOI] [PubMed] [Google Scholar]
  37. Webber C. E., Chettle D. R., Bowins R. J., Beaumont L. F., Gordon C. L., Song X., Blake J. M., McNutt R. H. Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation. Environ Health Perspect. 1995 Dec;103(12):1150–1153. doi: 10.1289/ehp.951031150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. deCastro F. J., Medley J. Lead in bone and hypertension. Matern Child Health J. 1997 Sep;1(3):199–200. doi: 10.1023/a:1026281731421. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES