ABSTRACT: BACKGROUND: Although there is considerable evidence for a loss of bone mass with weight loss, the few human studies on the relationship between weight cycling and bone mass or density have differing results. Further, very few studies assessed the role of dietary composition on bone mass during weight cycling. The primary objective of this study was to determine if a diet high in amylase-resistant starch (RS2), which has been shown to increase absorption and balance of dietary minerals, can prevent or reduce loss of bone mass during weight cycling. METHODS: Female Sprague-Dawley (SD) rats (n=84, age = 20 weeks) were randomly assigned to one of 6 treatment groups with 14 rats per group using a 2x3 experimental design with 2 diets and 3 weight cycling protocols. Rats were fed calcium-deficient diets without RS2 (controls) or diets high in RS2 (18% by weight) throughout the 21-week study. The weight cycling protocols were weight maintenance/gain with no weight cycling, 1 round of weight cycling, or 2 rounds of weight cycling. After the rats were euthanized bone mineral density (BMD) and bone mineral content (BMC) of femur were measured by dual energy X-ray absorptiometry, and concentrations of calcium, copper, iron, magnesium, manganese, and zinc in femur and lumbar vertebrae were determined by atomic absorption spectrophotometry. RESULTS: Rats undergoing weight cycling had lower femur BMC (p<0.05) and marginally lower BMD (p=0.09) than rats not undergoing weight cycling. In comparison to controls, rats fed RS2 had higher femur BMD (p<0.01) and BMC (p<0.05), as well as higher values for BMD and BMC measured at the distal end (p<0.001 and p<0.01) and femoral neck (p<0.01 and p<0.05). Consistent with these findings, RS2-fed rats also had higher femur calcium (p<0.05) and magnesium (p<0.0001) concentrations. They also had higher lumbar vertebrae calcium (p<0.05) and magnesium (p<0.05) concentrations. CONCLUSION: Weight cycling reduces bone mass. A diet high in RS2 can minimize loss of bone mass during weight cycling and may increase bone mass in the absence of weight cycling.