Osteopenia Induced by Long-term, Low- and High-level Exposure of the Adult Rat to Lead

The skeleton, the major site for Pb accumulation, is responsible for the largest fraction of the total body burden, but long-term effects of low-level exposure in adults remain unclear. In this study rats were exposed to low (0.01%; 100 ppm, LoPb) or high (0.5%, 5,000 ppm, HiPb) Pb, low calcium, feeding regimes for 1-12 months. Both LoPb and HiPb animals showed significant 12-month blood Pb levels [LoPb 21 +/- 3 micrograms/dl; HiPb 59 +/- 18; controls 3 +/- 1 (mean +/- SEM), p = 0.001]. Dual energy X-ray densitometry of the femur detected a significant decrease in bone density in HiPb animals by 3 months which remained significantly lowered through 12 months [3 months: HiPb: 0.498 +/- 0.011 (6) vs. control: 0.546 +/- 0.012 (6), p < 0.003]. By 12 months' density was also significantly lowered in LoPb animals (p = 0.001). Mineral analyses of ashed femurs showed a significant lead content after 1, 3, 9 and 12 months' exposure [1 month: LoPb, 0.020 +/- 0.002 (4) (% ash weight) vs control 0.008 +/- 0.0004 (4); HiPb 0.016 +/- 0.001 (8); control 0.007 +/- 0.0004 (6) (p < or = 0.002)]. Ca levels (% ash weight) were significantly lowered at 9 months in HiPb and 12 months in both groups (p < or = 0.04). Quantitative histomorphometry documented significantly elevated osteoid and resorptive trabecular surface features in both Pb groups. The LoPb design produced no overt renal functional abnormalities and resulted in blood Pb values comparable to those in man with modest environmental Pb exposure. The HiPb design resulted in development of lead nephropathy (more severe from months 6-12) and produced blood lead levels comparable to those seen in past industrial exposure. Findings show that Pb is incorporated into bone mineral after only 1 month's exposure to LoPb with significant osteopenia after 12 months' exposure; HiPb caused osteopenia by 3 months. No normal compensatory mechanism was elicited to maintain bone mass. Results stress renewed concern about the effects of cumulative, low-level lead exposure in our elderly population.