Exercise or Caloric Restriction Reduces Bone Resorption and Improves Cortical Bone Strength in Hyperphagic OLETF Rats
Authors: Ortinau Laura Christine , Richard Matthew , Linden Melissa , Rector R. Scott , Hinton Pamela 
Published: November 2023

Obesity and type 2 diabetes (T2D) continue to be major health concerns. Insulin resistance and/or T2D increase the risk of fracture by ~1.5‐fold, despite normal or increased bone mineral density (BMD). In this study, we evaluated the effects of voluntary wheel‐running exercise (EX) or caloric restriction (CR) on bone outcomes in obese, T2D Otsuka Long‐Evans Tokushima Fatty (OLETF) rats. Four‐week old, male OLETF rats were randomly assigned to one of three groups each fed a low‐fat chow diet: sedentary (O‐SED), EX (O‐EX), or a 30% CR (O‐CR) relative to the O‐SED group. Long‐Evans Tokushima Otsuka rats were used as a sedentary (L‐SED) lean, non‐diabetic control. At 40 weeks of age, body composition, total body bone mineral content (BMC) and BMD were measured by DXA. Cortical geometry of the femur was assessed using μCT. Cortical bone strength was measured by torsional loading of the femur to failure. Serum markers of bone formation (amino‐terminal propeptide of type I collagen, P1NP; osteocalcin, OC) and resorption (tartrate‐resistant acid phosphatase, TRAP5b; C‐terminal peptide of type I collagen, CTx) were measured using ELISA. Group differences were evaluated using a one‐way ANOVA. Body weight was included as a covariate for body‐size‐dependent bone outcomes. O‐SED had greater body weight (p<0.05), percent fat mass (p=0.059), glucose, and HbA1c as well as reduced insulin compared to the non‐obese L‐SED rats. EX or CR prevented the obesity‐associated changes in body weight, fat mass, and measures of glucose homeostasis observed in O‐SED. CR reduced total body BMD compared to L‐SED, O‐SED, and O‐EX rats (p<0.05); BMC did not differ among groups. O‐SED had lower OC than L‐SED (p=0.057), and O‐EX and O‐CR had lower OC than both O‐SED and L‐SED. There were no group differences in P1NP. O‐SED had ~3‐fold greater CTx compared to L‐SED; EX or CR prevented this increase in CTx. TRAP5b was significantly lower in O‐SED vs. L‐SED, and O‐EX and O‐CR had lower TRAP5b than L‐SED and O‐SED. O‐SED had reduced femur length and increased femur diameter, cortical area and total area vs. L‐SED. CR, but not EX, attenuated these changes in cortical structure. O‐CR had significantly greater femur length and smaller total and cortical area compared with O‐SED. Cortical thickness was similar among groups. Torsional stiffness was increased by obesity (O‐SED vs. L‐SED p<0.05, adjusted for body weight), while shear modulus of elasticity (G), ultimate tensile strength (Su), and maximal torque (Tmax) did not differ between O‐SED and L‐SED. EX or CR significantly increased G and Su compared to O‐SED and L‐SED, and O‐EX had greater Ks than all other groups. In conclusion, either EX or CR attenuated the increase in bone resorption observed in obese O‐SED rats and increased cortical bone strength relative to both lean and obese animals.Support or Funding InformationThis work was supported with the use of facilities at the Harry S Truman Memorial Veterans hospital in Columbia, MO. This work was partially supported by a VA Career Development Award and by the Department of Nutrition & Exercise Physiology.