Bone density-related predictors of blood lead and risk of lead toxicity among peri- and postmenopausal women in the United States population

Abstract

Background. Though environmental exposure to lead has diminished substantially in recent decades, lead exposure is still an ongoing public health concern. Chronic exposure to low levels of lead results in accumulation of lead in the skeleton, where 90-95% of the body's lead stores reside. Mounting evidence suggests that lead retained in bone may be mobilized back into the circulation during post-menopausal bone loss. Recent research has linked lead in the blood, at levels previously thought to be safe, to a number of adverse health outcomes in adults, including increased risk of hypertension, altered kidney function, and neurocognitive deficits. Hormone replacement therapy (HRT) prevents bone loss and may be also an important determinant of blood lead levels. Methods. A toxicokinetic model was developed to predict the relationship between bone lead levels and blood lead levels over the menopausal transition. Also, data on 1,815 women aged 40--59 from the third National Health and Nutrition Examination Survey (NHANES III) were analyzed to assess the degree to which: (1) blood lead levels were influenced by bone density-related factors; and (2) blood lead concentrations and bone density-related predictors of blood lead concentrations were associated with selected, concurrently measured health outcomes. Results. The toxicokinetic model predicted small, transient increases in blood lead levels associated with post-menopausal bone loss. Analysis of the NHANES data found bone density-related factors to be significant predictors of the blood lead levels of US women. The adjusted mean blood lead concentration of pre-menopausal women was 2.9 mug/dl compared with 3.4 mug/dl in post-menopausal women (p < 0.01). Post-menopausal women who were current users of HRT had adjusted blood lead levels of 2.5 mug/dl compared to 3.5 mug/dl and 3.6 mug/dl in never and past users of HRT, respectively (p < 0.0001). The adjusted relative odds of diastolic hypertension in the highest quartile of blood lead (mean 4.8 mug/dl) compared to that of the lowest (mean 0.90 mug/dl) was 3.7 (95% Cl 1.3-10.8), with a strong dose-response. Blood lead levels were not significantly associated with any of the measures of neurocognitive function after adjustment for relevant covariates. Similar results were observed when data were examined in each category of race/ethnicity separately. Conclusions. These findings are consistent with the theory that menopausal bone loss is accompanied by age-independent increases in blood lead levels. This investigation also found that lead is associated with an increased prevalence of diastolic hypertension at low levels in the US population. These findings offer support for continued efforts by the public health community to develop policies aimed at reducing environmental exposure to lead.