Benchmark dose for cadmium-induced osteoporosis in women.

We applied a hybrid approach to estimate the benchmark dose (BMD) and the lower 95% confidence limit (BMDL) for cadmium-induced bone effects in a population with low environmental exposure. Morning urine samples were collected by 794 Swedish women, aged 53-64 years, participating in a population-based study. We measured urinary cadmium (U-Cd), a marker of long-term exposure, and bone mineral density, expressed as its T-score (reference: 20-year old women) of the non-dominant wrist. BMD and BMDL, adjusted for relevant covariates, corresponding to an additional risk (BMR) of 5% or 10% were calculated, with the background risk at zero exposure set at 1% or 5%. With a BMR of 5% and a background risk of having low bone mineral density (at U-Cd = 0) of 1% or 5% (corresponding to T-score cut-offs -2.75 and -2.09, respectively), the BMD of U-Cd ranged 1.8-3.7 microg/g creatinine, and the BMDL ranged 1.0-2.1 microg/g creatinine. For a 5% BMR of osteoporosis (T-score < -2.5), the BMD was 2.9 microg/g creatinine and the BMDL 1.6 microg/g creatinine. The lowest obtained BMD of U-Cd for wrist bone mineral density was only slightly higher than the lowest reference concentration previously reported for cadmium-related kidney effects. Our results provide additional scientific support for the low tolerably weekly intake (TWI) of cadmium set by the European Food Safety Authority in 2009. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.