Combination Of Exercise And Soy Protein Improves Bone Measures And Vascular Calcification In Uremic Mice

Abstract

Cardiovascular disease (CVD) is the leading cause of death for individuals with chronic kidney disease (CKD), and calcium deposits in the vasculature may partially explain the increase in risk compared to age-and sex-matched controls. Individuals with CKD are also at increased risk for CKD-mineral bone disorder, leading to significantly elevated fracture risk. These conditions may be related to the abnormal mineral metabolism commonly seen in this population, and current pharmacological interventions have been unsuccessful in treating these conditions simultaneously. Soy protein containing phytoestrogens and endurance exercise training have shown potential for improving these disease conditions. PURPOSE: To determine the efficacy of endurance exercise training and soy protein, alone and in combination, on bone and vascular measures in a mouse model of uremia. METHODS: At 8 weeks of age, 60 female Apolipoprotein E-/- mice underwent a two-step surgical procedure to induce uremia. At 12 weeks, they were randomized to one of four treatment groups, and remained on the treatment for 4 months: sedentary/control diet (n=16), sedentary/soy protein diet (n=18), exercise/control diet (n=14), and exercise/soy protein diet (n=12). The control diet contained 20% casein compared to the 20% soy protein, and the exercise consisted of treadmill running 5 days a week for 45 minutes at 18m/min. RESULTS: Both exercise alone and soy protein diet plus exercise compared to sedentary controls produced a modest 7% decrease in vascular calcium score in the proximal aorta (p=0.03) as measured by Alizarin Red staining. Soy plus exercise significantly improved several bone measures including a 52% increase in bone volume fraction (BV/TV p<0.01), a 107% increase in trabecular connective density (p<0.001), a 47% increase in trabecular number (p<0.001), and a 60% decrease in trabecular separation as measured by microCT. Neither exercise nor soy protein alone improved any bone measures. CONCLUSION: Endurance exercise training together with a soy protein diet produced significant improvements in the bone and vasculature suggesting that a combination of dietary and lifestyle changes may be beneficial for treating both vascular calcification and bone disorders in CKD. Supported by the Illinois Soy Board.