The effects of caloric restriction (CR) on the skeleton are well studied in adult rodents, and include lower cortical bone mass but higher trabecular bone volume. Much less is known about how CR affects bone mass in young, rapidly growing animals. This is an important problem because low caloric intake during skeletal acquisition in humans, as in anorexia nervosa, is associated with low bone mass, increased fracture risk, and osteoporosis in adulthood. To explore this question, we tested the effect of caloric restriction on bone mass and microarchitecture during rapid skeletal growth in young mice.
At 3 wks of age we weaned male C57Bl/6J mice onto 30% caloric restriction (CR, 10% Kcal/fat) or normal diet (N, 10% Kcal/fat). Outcomes at 6 (N=4/group) and 12 wks of age (N=8/group) included body mass, femur length, serum leptin and IGF-1, whole body bone mineral density (WBBMD, g/cm2), cortical and trabecular bone architecture at the midshaft and distal femur, bone formation and cellularity, and marrow fat measurement.
Compared to N, CR mice had 52% and 88% lower serum leptin and 33% and 39% lower serum IGF-1 at 6 and 12 wks of age (p<0.05 for all). CR mice were smaller, with lower bone mineral density, trabecular and cortical bone properties. Bone formation indices were lower, while bone resorption indices were higher (p<0.01 for all) in CR vs. N. Despite having lower %body fat, bone marrow adiposity was dramatically elevated in CR vs. N (p<0.05).
Caloric restriction in young, growing mice is associated with impaired skeletal acquisition, low leptin and IGF-1 levels, and high marrow adiposity. These results support the hypothesis that caloric restriction during rapid skeletal growth is deleterious to cortical and trabecular bone mass and architecture, in contrast to potential skeletal benefits of CR in aging animals.