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      Bone Resorption and Environmental Exposure to Cadmium in Women: A Population Study

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          Abstract

          Background

          Environmental exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction.

          Objective

          We sought evidence for a direct osteotoxic effect of cadmium in women.

          Methods

          We randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with environmental cadmium exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent exposure, respectively. We assessed the multivariate-adjusted association of exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density.

          Results

          In all women, the effect sizes associated with a doubling of lifetime exposure were 8.4% ( p = 0.009) for HP, 6.9% ( p = 0.10) for LP, 0.77 mmol/day ( p = 0.003) for urinary calcium, –0.009 g/cm 2 ( p = 0.055) for proximal forearm bone density, and –16.8% ( p = 0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were –0.01223 g/cm 2 ( p = 0.008) for distal forearm bone density, 4.7% ( p = 0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent exposure were 7.2% ( p = 0.001) for urinary HP, 7.2% ( p = 0.021) for urinary LP, –9.0% ( p = 0.097) for serum parathyroid hormone, and 5.5% ( p = 0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein > 338 μg/day).

          Conclusions

          In the absence of renal tubular dysfunction, environmental exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones.

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          Most cited references 47

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          Osteoporosis: a still increasing prevalence.

          It is estimated that over 200 million people worldwide have osteoporosis. The prevalence of osteoporosis is continuing to escalate with the increasingly elderly population. The major complication of osteoporosis is an increase in fragility fractures leading to morbidity, mortality, and decreased quality of life. In the European Union, in 2000, the number of osteoporotic fractures was estimated at 3.79 million. A baseline fracture is a very strong predictor of further fractures with 20% of patients experiencing a second fracture within the first year. The costs to health care services are already considerable and, on current trends, are predicted to double by 2050. The direct costs of osteoporotic fractures to the health services in the European Union in the year 2000 were estimated at 32 billion Euros. Guidelines for the diagnosis and treatment of osteoporosis are available in many countries; however, implementation is generally poor despite the availability of treatments with proven efficacy. Programs to increase awareness of osteoporosis and its outcomes are necessary for healthcare specialists and the general public. Earlier diagnosis and intervention prior to the first fracture are highly desirable.
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            Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstuffs and Cigarette Smoke

            Cadmium is a cumulative nephrotoxicant that is absorbed into the body from dietary sources and cigarette smoking. The levels of Cd in organs such as liver and kidney cortex increase with age because of the lack of an active biochemical process for its elimination coupled with renal reabsorption. Recent research has provided evidence linking Cd-related kidney dysfunction and decreases in bone mineral density in nonoccupationally exposed populations who showed no signs of nutritional deficiency. This challenges the previous view that the concurrent kidney and bone damage seen in Japanese itai-itai disease patients was the result of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and calcium. Further, such Cd-linked bone and kidney toxicities were observed in people whose dietary Cd intakes were well within the provisional tolerable weekly intake (PTWI) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives of 1 μg/kg body weight/day or 70 μg/day. This evidence points to the much-needed revision of the current PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is accumulating and Cd effects on reproductive outcomes have begun to emerge.
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              Gender differences in the disposition and toxicity of metals.

              There is increasing evidence that health effects of toxic metals differ in prevalence or are manifested differently in men and women. However, the database is small. The present work aims at evaluating gender differences in the health effects of cadmium, nickel, lead, mercury and arsenic. There is a markedly higher prevalence of nickel-induced allergy and hand eczema in women compared to men, mainly due to differences in exposure. Cadmium retention is generally higher in women than in men, and the severe cadmium-induced Itai-itai disease was mainly a woman's disease. Gender differences in susceptibility at lower exposure are uncertain, but recent data indicate that cadmium has estrogenic effects and affect female offspring. Men generally have higher blood lead levels than women. Lead accumulates in bone and increased endogenous lead exposure has been demonstrated during periods of increased bone turnover, particularly in women in pregnancy and menopause. Lead and mercury, in the form of mercury vapor and methylmercury, are easily transferred from the pregnant women to the fetus. Recent data indicate that boys are more susceptible to neurotoxic effects of lead and methylmercury following exposure early in life, while experimental data suggest that females are more susceptible to immunotoxic effects of lead. Certain gender differences in the biotransformation of arsenic by methylation have been reported, and men seem to be more affected by arsenic-related skin effect than women. Experimental studies indicate major gender differences in arsenic-induced cancer. Obviously, research on gender-related differences in health effects caused by metals needs considerable more focus in the future.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                June 2008
                25 February 2008
                : 116
                : 6
                : 777-783
                Affiliations
                [1 ] Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven, Leuven, Belgium
                [2 ] Department of Physiology, School for Physiology, Nutrition and Consumer Sciences, North-West University, Potchefstroom, South Africa
                [3 ] Section of Experimental Medicine and Endocrinology, Department of Experimental Medicine, University of Leuven, Leuven, Belgium
                [4 ] Section of Social and Economic Geography, Department of Geography and Geology, University of Leuven, Leuven, Belgium
                [5 ] Industrial Toxicology and Occupational Medicine Unit, Department of Public Health, Université catholique de Louvain, Brussels, Belgium
                Author notes
                Address correspondence to J.A. Staessen, Studie-coördinatiecentrum, Laboratorium Hypertensie, Campus Gasthuisberg, Herestraat 49, Box 702, B-3000 Leuven, Belgium. Telephone: 32-16-34-7104. Fax: 32-16-34-7106. E-mail: jan.staessen@ 123456med.kuleuven.ac.be

                H.A. Roels was a member of the scientific review panel (health) for the Voluntary Risk Assessment Report on Lead and Lead Compounds drafted by ILZRO (Research Triangle Park, NC, USA), the European Bio-Research Consultants (EBRC Consulting GmbH, Hannover, Germany), and the Lead Development Association International (LDAint, London, UK) in the framework of the EC Chemical Bureau Existing Substances Programme. All other authors declare they have no competing financial interests.

                Article
                ehp0116-000777
                10.1289/ehp.11167
                2430234
                18560534
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                Categories
                Research

                Public health

                pyridinium crosslinks, cadmium, bone

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