Ad libitum eating and reduced exercise resolve impaired bone integrity after prolonged reductions in energy availability in mature female rodents

Reduced energy availability (EA) results in loss of bone mass and disruption of endocrine regulators of bone integrity, even in very active individuals. Our aim was to determine whether 12 weeks of less exercise and ad libitum eating would enable recovery of deficits incurred during 12 weeks of reduced EA, hypothesizing recovery would be improved in exercising rats. Female rats (n=64, 5 months old) were randomized to sedentary (SED) or exercise (EX) conditions and, within each group, to adlib-fed (ADLIB) or severe energy restriction (SEV-ER). Energy intake was restricted in all SEV-ER rats and exercise volume in SEV-ER EX rats calculated to produce equivalent 30% reductions in EA. After 12 weeks, SEV-ER EX rats exhibited no losses in lean/fat mass and total bone mass (DXA), metaphyseal %BV/TV, and distal femur and femoral neck vBMD (by pQCT), and higher values for osteoblast activity than observed in SEV-ER SED animals. EX did not protect against declines in serum leptin and IGF-I. Half of each group recovered for 12 weeks, eating ADLIB and (in EX rats) reducing running volume by 50%. After 4 weeks recovery, body weight and energy availability for all SEV-ER rats matched those of ADLIB rats. By 12 weeks, there were no significant differences among groups for all variables. These results demonstrate that bone mass/microarchitecture and osteoblast activity observed in SED animals can return to normal levels after a period of ad libitum eating, as can IGF-I/leptin in exercising rats with reduced exercise and ADLIB eating of the same duration as the preceding reduced EA.