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Agneta Åkesson,¹ Per Bjellerup,² Thomas Lundh,³ Jonas Lidfeldt,⁴ Christina Nerbrand,⁵ Göran Samsioe,⁶ Staffan Skerfving,³ and Marie Vahter¹

¹Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; ²Department of Clinical Chemistry, Karolinska University Hospital, Huddinge, Sweden; ³Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden; ⁴Department of Community Health, Malmö University Hospital, Malmö, Sweden; ⁵Department of Medicine, and ⁶Department of Gynecology and Obstetrics, University Hospital, Lund, Sweden

Abstract
High cadmium exposure is known to cause bone damage, but the association between low-level cadmium exposure and osteoporosis remains to be clarified. Using a population-based women's health survey in southern Sweden [Women's Health in the Lund Area (WHILA) ] with no known historical cadmium contamination, we investigated cadmium-related effects on bone in 820 women (53-64 years of age) . We measured cadmium in blood and urine and lead in blood, an array of markers of bone metabolism, and forearm bone mineral density (BMD) . Associations were evaluated in multiple linear regression analysis including information on the possible confounders or effect modifiers: weight, menopausal status, use of hormone replacement therapy, age at menarche, alcohol consumption, smoking history, and physical activity. Median urinary cadmium was 0.52 µg/L adjusted to density (0.67 µg/g creatinine) . After multivariate adjustment, BMD, parathyroid hormone, and urinary deoxypyridinoline (U-DPD) were adversely associated with concentrations of urinary cadmium (p < 0.05) in all subjects. These associations persisted in the group of never-smokers, which had the lowest cadmium exposure (mainly dietary) . For U-DPD, there was a significant interaction between cadmium and menopause (p = 0.022) . Our results suggest negative effects of low-level cadmium exposure on bone, possibly exerted via increased bone resorption, which seemed to be intensified after menopause. Based on the prevalence of osteoporosis and the low level of exposure, the observed effects, although slight, should be considered as early signals of potentially more adverse health effects. Key words: biochemical bone markers, bone mineral density, cadmium, lead, osteoporosis, women. Environ Health Perspect 114:830-834 (2006) . doi:10.1289/ehp.8763 available via http://dx.doi.org/ doi:10.1289/ehp.8763 available via http://dx.doi.org/ [Online 2 February 2006]

Address correspondence to A. Åkesson, Division of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden. Telephone: 46-8-524-875-42. Fax: 46-8-33-70-39. E-mail: agneta.akesson@imm.ki.se

We thank U. Strömberg for statistical advice. We also thank the late A. Schütz, H. Ottosson, A. Akantis, A.-M. Åberg, and B. Erdling.

Funding was provided by the Swedish Research Council/Medicine ; the Medical Faculty of Lund University ; Karolinska Institutet ; the National Swedish Environmental Protection Agency ; the Swedish Foundation for Strategic and Environmental Research ; the Swedish Society of Medicine ; Primary Care, and R&D, County Council of Skåne ; the Swedish Research Council for Environment, Agricultural Sciences, and Spatial Planning ; and the Swedish Council for Working Life and Social Research.

The authors declare they have no competing financial interests.

Received 21 October 2005 ; accepted 2 February 2006.