New bone drug benefit: less skeletal lead released. (Science Selections).

Alendronate (trade name Fosamax) is a potent biphosphonate drug commonly prescribed to reduce or reverse the loss of bone density in postmenopausal women. In postmenopausal osteoporosis, the hormonal changes associated with menopause cause the normal balance between bone resorption (loss) and formation to be thrown off, with increased resorption resulting in less dense bones that are more prone to fracture. Biphosphonates inhibit bone resorption, allowing bones to maintain their density. Now, according to the results of a two-year pilot study conducted by a team of Australian researchers led by Brian Gulson of Macquarie University, antiresorptive therapy may also be useful in warding off the deleterious health effects of elevated blood lead levels by inhibiting lead's release from the skeleton into the bloodstream [EHP 110:1017-1023].

The skeleton is the main reservoir of lead within the body. Times of physiologic stress such as menopause can result in the release of stored lead into the blood through demineralization, the same process that causes calcium to be released from bone. Previous studies have shown that menopausal and postmenopausal women tend to have higher blood lead levels than premenopausal women. This is an issue of concern because elevated blood lead levels in adults have been correlated with hypertension, decreased renal function, impaired neurocognitive function, and Alzheimer disease.

The subjects consisted of 3 premenopausal women, 2 perimenopausal women (perimenopause being the years before menopause begins when estrogen levels begin to fall), 2 postmenopausal woman, and 3 men. Each of the 10 subjects was given alendronate for 6 months. Blood and urine samples were collected monthly for 7-9 months before, 3 months during, and up to 6 months after the treatment. These samples were analyzed for markers of bone turnover (which increases during menopause) and for lead isotopes, allowing the researchers to assess the effects of the antiresorptive therapy on blood lead levels.

The subjects were recent immigrants to Australia. They were chosen to take advantage of the fact that the lead isotopic composition, or "signature," in multigenerational Australian residents is different from that of people from other countries. Thus, the migrant subjects would be expected to have blood lead signatures characteristic of their countries of origin (due to the release of stored lead from bone) as well as the Australian lead isotopes (due to environmental exposure since their arrival). By tracking changes in the ratio of these lead isotopes, the researchers were able to specifically monitor the level of blood lead coming from bone sources and thus trace the effects of alendronate on bone lead release.

As the authors had predicted, there were significant decreases in the lead isotopic ratio in the migrant subjects during the treatment period--that is, the subjects' blood lead was increasingly composed more of Australian lead--indicating that the inhibition of bone resorption by the drug was in fact reducing the release of skeletal lead. Further, the average overall blood lead levels in the migrant subjects decreased by about 20% during the treatment.

Although the number of subjects studied was small, this pilot study is still the most extensive to date of the effect of antiresorptive agents on blood lead that apparently comes from bone sources. It raises the tantalizing possibility that antiresorptive therapy, in addition to its proven effectiveness in preventing osteoporosis, could also be used in older women and men to prevent the adverse health effects associated with elevated concentrations of lead in the blood.