Maureen J. Devlin

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 weeks of age, we weaned male C57Bl/6J mice onto 30% caloric restriction (10% kcal/fat) or normal diet (10% kcal/fat). Outcomes at 6 (n = 4/group) and 12 weeks of age (n = 8/group) included body mass, femur length, serum leptin and insulin-like growth factor 1 (IGF-1) values, whole-body bone mineral density (WBBMD, g/cm(2)), cortical and trabecular bone architecture at the midshaft and distal femur, bone formation and cellularity, and marrow fat measurement. Compared with the normal diet, CR mice had 52% and 88% lower serum leptin and 33% and 39% lower serum IGF-1 at 6 and 12 weeks of age (p < .05 for all). CR mice were smaller, with lower bone mineral density, trabecular, and cortical bone properties. Bone-formation indices were lower, whereas bone-resorption indices were higher (p < .01 for all) in CR versus normal diet mice. Despite having lower percent of body fat, bone marrow adiposity was elevated dramatically in CR versus normal diet mice (p < .05). Thus we conclude that 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.

How reliable are reconstructions of body mass and joint function based on articular surface areas? While the dynamic relationship between mechanical loading and cross-sectional geometry in long bones is well-established, the effect of loading on the subchondral articular surface area of epiphyses (hereafter, articular surface area, or ASA) has not been experimentally tested. The degree to which ASA can change in size and shape is important, because articular dimensions are frequently used to estimate body mass and positional behavior in fossil species. This study tests the hypothesis that mechanical loading influences ASA by comparing epiphyses of exercised and sedentary sheep from three age categories: juvenile, subadult, and adult (n = 44). ASA was measured on latex molds of subchondral articular surfaces of 10 epiphyses from each sheep. Areas were standardized by body mass, and compared to diaphyseal cross-sectional geometrical data. Nonparametric statistical comparisons of exercised and control individuals found no increases in ASA in response to mechanical loading in any age group. In contrast, significant differences in diaphyseal cross-sectional geometry were detected between exercised and control groups, but mostly in juveniles. The conservatism of ASA supports the hypothesis that ASA is ontogenetically constrained, and related to locomotor behavior at the species level and to body mass at the individual level, while variations in diaphyseal cross-sectional geometry are more appropriate proxies for individual variations in activity level.

Wolff's law of trajectorial orientation proposes that trabecular struts align with the orientation of dominant compressive loads within a joint. Although widely considered in skeletal biology, Wolff's law has never been experimentally tested while controlling for ontogenetic stage, activity level, and species differences, all factors that may affect trabecular bone growth. Here we report an experimental test of Wolff's law using a within-species design in age-matched subjects experiencing physiologically normal levels of bone strain. Two age-matched groups of juvenile guinea fowl Numida meleagris ran on a treadmill set at either 0 degrees (Level group) or 20 degrees (Incline group), for 10 min per day over a 45-day treatment period. Birds running on the 20 degrees inclined treadmill used more-flexed knees than those in the Level group at midstance (the point of peak ground reaction force). This difference in joint posture enabled us to test the sensitivity of trabecular alignment to altered load orientation in the knee. Using a new radon transform-based method for measuring trabecular orientation, our analysis shows that the fine trabecular bone in the distal femur has a high degree of correspondence between changes in joint angle and trabecular orientation. The sensitivity of this response supports the prediction that trabecular bone adapts dynamically to the orientation of peak compressive forces.