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

Abstract

Exposure to lead is still an international public health problem, despite major reductions in its use in industrial processes in developed countries (1). The neurotoxic effects of lead in the fetus, neonate, and infant are well recognized (2). The main reservoir of lead within the body is the skeleton and, until recently, lead was considered to be relatively immobile in this compartment. Recent studies using the stable lead isotope fingerprinting method in nonhuman primates (3,4) as well as in humans (5,6) indicate that lead, like calcium, is mobilized from the maternal skeleton and transferred to the fetus and neonate during pregnancy and lactation. Other times of physiologic stress that could result in additional release of lead from the skeleton include menopause (7). In a preliminary assessment of data from the Third National Health and Nutritional Examination Survey (NHANES III), higher blood lead (BPb) levels were observed in postmenopausal compared with premenopausal women (3.9 vs. 2.6 µg/dL), consistent with the increased bone turnover that occurs during the hormonal changes of menopause. Moreover, higher BPb levels were associated with lower bone density in perimenopausal women (8). Similar relationships in BPb and menopause were noted earlier (9). In a study of 903 women 35-64 years of age from Mexico City, the highest BPb levels were observed in women 47-50 years of age, with a mean difference between pre-and postmenopausal women of 0.76 µg/dL (10). These higher blood levels could have significant health implications because increased BPb levels in adults have been correlated with hypertension (11-16), decreased renal function (17), impaired neurocognitive function (18), and Alzheimer disease (19).Antiresorptive agents that inhibit resorption in the bone remodeling process may reduce or even reverse the demineralization process documented during pregnancy and lactation, observed in perimenopausal women (20), and seen in men and women with corticosteroid-induced osteoporosis (21). Thus, these agents may have the additional benefit of preventing increases in BPb levels commonly seen in these life stages. During pregnancy, calcium supplementation is associated with lower BPb levels (22-24), although calcium given alone has not been proven to reverse the loss of bone mineral density during pregnancy (24) or in postmenopausal subjects (25). In menopausal women, antiresorptive agents such as hormone replacement therapy (HRT) and bisphosphonates are capable of preventing loss of bone density (20,25,26). Postmenopausal women taking HRT have been observed to have significantly higher cortical bone lead concentrations than those not taking HRT (27). To our knowledge there have been no prospective studies to document the effect of antiresorptive agents on BPb levels in healthy adults.We performed a pilot study of the effect of a potent bisphosphonate (alendronate) administered over a 6-month period on BPb levels and other markers of bone turnover in healthy pre-and postmenopausal women and men. The aim of this s...

Relationship of Blood Lead Levels to Incident Nonspine Fractures and Falls in Older Women: The Study of Osteoporotic Fractures

“…The association between lead and fracture may be caused by a direct effect of lead on bone strength or may simply be a marker of high bone turnover. Small studies of bisphosphonates (50) and hormone therapy (5) showed that treatments that reduce bone turnover resulted in a lower skeletal lead release (50) . In our study, women who reported using estrogen had lower lead levels.…”

Bone lead (Pb) content at the tibia is associated with thinner distal tibia cortices and lower volumetric bone density in postmenopausal women

“…Although no bone turnover markers were measured in the present study, the cohort consisted of women half of whom had fractures within the last 14 years, and many of whom were not on antiresorptive therapy. One study by Gulson showed data that suggested that bisphosphonate therapy can prevent the release of lead from bone into the bloodstream [30]. However, individuals on antiresorptive therapy in the present cohort showed marginally larger bone lead content than those not on antiresorptives.…”

The Association between Blood Lead Levels and Osteoporosis among Adults—Results from the Third National Health and Nutrition Examination Survey (NHANES III)

“…In other words, it is possible that increased bone turnover produced an increase in blood lead from the endogenous release of lead from the bone. Using stable lead isotope fingerprinting methods, Gulson et al (1998, 2002) found that lead can be mobilized from the skeleton into the blood. This issue has been raised in the literature.…”