Endocrinol Metab.  2014 Mar;29(1):70-76. 10.3803/EnM.2014.29.1.70.

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

  • 1Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea. injkim@pusan.ac.kr
  • 2Medical Research Institute, Pusan National University School of Medicine, Busan, Korea.
  • 3Department of Rehabilitation Medicine, Pusan National University School of Medicine, Busan, Korea.
  • 4Pusan National University Collegy of Pharmacy, Busan, Korea.
  • 5Department of Nuclear Medicine, Pusan National University School of Medicine, Busan, Korea.
  • 6Kim Yong Ki Internal Medicine Clinic, Busan, Korea.


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.
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.
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-alpha levels decreased only in OLETF rats (P=0.009).
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.


Caloric restriction; Bone density; Diabetes mellitus, type 2

MeSH Terms

Absorptiometry, Photon
Alkaline Phosphatase
Body Weight
Bone Density*
Caloric Restriction*
Diabetes Mellitus, Type 2
Models, Animal
Rats, Inbred OLETF
Tumor Necrosis Factor-alpha
Weight Loss
Alkaline Phosphatase
Tumor Necrosis Factor-alpha


  • Fig. 1 After 4 weeks of caloric restriction (CR), the bone mineral density of the whole femur decreased in Long-Evans Tokushima Otsuka (LETO) rats and was maintained in Otsuka Long-Evans Tokushima fatty (OLETF) rats. AL, ad libitum. aP<0.05 compared with baseline.

  • Fig. 2 After 4 weeks of caloric restriction (CR), leptin levels decreased in Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima fatty (OLETF) rats. In OLETF rats, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels decreased after CR, while 25-hydroxyvitamin D (25(OH)D) levels increased. AL, ad libitum. aP<0.01 compared with LETO-AL rats; bP<0.01 compared with OLETF-AL rats.


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