(P17-002-24) Combinatorial Effects of Zinc Deficiency and Arsenic Exposure on Bone in Growing Female Mice

Objectives: Arsenic contamination in the groundwater co-exists in regions of the world that are prone to Zinc (Zn) deficiency. While Zn deficiency is detrimental to the growing skeleton, it remains unknown if arsenic co-exposure exaggerates the adverse skeletal effects of Zn deficiency. The goal of this study was to evaluate the effect of Zn deficiency (severe and marginal) and arsenic co-exposure on bone mass and cortical and cancellous bone microarchitecture in growing mice.

Methods: 3-4-week-old female C57BL/6 mice were randomized to severe Zn deficient ( < 0.5 mg Zn/kg diet), marginal Zn deficient (6 mg Zn/kg diet), or Zn adequate (30 mg Zn/kg diet) diets. Mice were given 0, 50 or 500 ppb sodium arsenite in drinking water for 4-6 weeks (n=8/ treatment group). Femurs were collected and evaluated using dual energy x-ray absorptiometry and microcomputed tomography.

Results: Severe Zn deficiency resulted in lower total femur bone mineral density, lower midshaft cortical thickness, and lower cancellous bone volume fraction in distal femur metaphysis and epiphysis. Arsenite exposure did not alter the detrimental effects of consuming a severe Zn-deficient diet. Neither marginal Zn deficiency nor marginal Zn deficiency and arsenite co-exposure affected the endpoints measured.

Conclusions: In summary, severe but not marginal Zn deficiency, in rapidly growing mice, lowered bone mass and density and altered cortical and cancellous bone microarchitecture. In contrast, short-term exposure to environmentally relevant concentrations of arsenite had little effect on bone in either severely Zn-deficient or marginally Zn-deficient mice.

Funding Sources: This work was supported the by National Institute of Food and Agriculture- Agricultural Experimental Station Multi-state [W5002] and Oregon Agricultural Experiment Station [OR00735], the National Institutes of Health Competing Revision to 1R01ES021100, Revision Awards for Creating Virtual Consortium for Translational/Transdisciplinary Environmental Research (ViCTER), and National Institute of Environmental Health Sciences P30 ES000210.