Short-Term Caloric Restriction Does Not Reduce Bone Mineral Density in Rats with Early Type 2 Diabetes

BACKGROUND: The effect of caloric restriction (CR) in the setting of diabetes on bone metabolism has not yet been fully studied. The aim of this study is to determine if short-term CR alters bone mass and metabolism in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: Four groups (n=5) were created: OLETF rats with food ad libitum (AL), OLETF rats with CR, Long-Evans Tokusima Otsuka (LETO) rats with food AL, and LETO rats with CR. The CR condition was imposed on 24-week-old male rats using a 40% calorie reduction for 4 weeks. The effect of CR on femoral bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry. Serum markers were measured by immunoassay. RESULTS: After 4 weeks of CR, body weight decreased in both strains. The BMD decreased in LETO rats and was maintained in OLETF rats. After adjustment for body weight, BMD remained lower in LETO rats (P=0.017) but not OLETF rats (P=0.410). Bone-specific alkaline phosphatase levels decreased in LETO rats (P=0.025) but not in OLEFT rats (P=0.347). Serum leptin levels were reduced after CR in both strains, but hyperleptinemia remained in OLETF rats (P=0.009). CR increased 25-hydroxyvitamin D levels in OLETF rats (P=0.009) but not in LETO rats (P=0.117). Additionally, interleukin-6 and tumor necrosis factor-α levels decreased only in OLETF rats (P=0.009). CONCLUSION: Short-term CR and related weight loss were associated with decreases of femoral BMD in LETO rats while BMD was maintained in OLETF rats. Short-term CR may not alter bone mass and metabolism in type 2 diabetic rats.