Time-Restricted Feeding Maintains Bone Microarchitecture in Female Mice

Objectives: Traditionally, dietary approaches for improving bone health in aging have involved changes in diet composition or supplementation. More recently, the potential protective effects of intermittent fasting have been investigated. Time-restricted feeding (TRF) is an increasingly popular and practical method of intermittent fasting that involves consuming food during a short time window. TRF has shown many health benefits without the need for changes in diet; however, the impact of TRF on bone health remains unclear. The objective of our study was to address this knowledge gap by examining the impact of TRF on bone microstructure in the context of habitual consumption of a low-fat or Western-type diet. Methods: To investigate if TRF would attenuate age-related declines in bone, female C57BL/6J (10-week-old) mice were randomly assigned to one of four experimental groups (n=8/group) for 9 weeks: 1) ad libitum low-fat diet (LFD); 2) TRF LFD; 3) ad libitum high-fat, high sucrose diet (HFHSD); or 4) TRF HFHSD. TRF groups had access to food for 8 hours per day during the dark cycle. Food intake as well as phenotypic parameters including body weight and composition, bone (femur, tibia, and lumbar spine) microarchitecture, and in vitro osteoclast formation assays were assessed in these mice. Results: Compared to baseline skeletally mature mice, prolonged TRF significantly attenuated age-related declines in trabecular bone microstructure within the femur and tibia. TRF of a LFD significantly improved trabecular bone microstructure in the tibia and lumbar spine without changing body weight or energy intake. Within the context of HFHSD, TRF decreased weight gain, percent body fat, and decreased fasting blood glucose, while maintaining muscle mass. These beneficial effects were evident despite consuming equivalent food and energy compared to the ad libitum HFHSD group. Irrespective of diet, TRF increased brown adipose tissue compared to diet-matched ad libitum controls. Mechanistically, TRF significantly decreased the formation of bone destructive osteoclasts, TRAP activity, and expression of key osteoclast phenotypic genes. Conclusions: Our data suggest that TRF without caloric restriction is a previously unrecognized simple, yet effective approach to protect from age-related declines in bone microstructure. Funding Sources: Arizona State University.