0113 Chronic Sleep Restriction Decreases Mature Bone Health in the Rodent Model

Abstract Introduction Chronic sleep restriction (SR) results in numerous disease risks. One emerging disease risk is osteoporosis, brought to light by both epidemiological studies and initial experimental findings. The purpose of the present study in rats was to determine the extent to which chronic SR affects bone quality (e.g., microstructure) and integrity (e.g., fracture risk) in middle age, the age interval of numerous epidemiological findings. The laboratory rat is a preferred animal for evaluation of bone health relevant to humans because of its well-characterized skeleton, comparable biochemical markers, and similar methodology for measurement of bone density and microarchitecture. Methods Male Sprague-Dawley rats began study at 11–12 months of age, at which time bone remodeling prevails over bone modeling, and linear growth has declined to a negligible level. Using a well-validated paradigm, rats underwent repeated long bouts sleep reduction of 35% of normal values, interspersed with “weekends” of sleep ad libitum to model a workweek. A duration of 66 days allowed intrinsic changes to manifest, theoretically equivalent to 6.5 years in humans. Ambulation control (AC) rats were studied under similar experimental conditions but with validated, lengthier opportunities for sleep. Biomechanical testing of harvested femurs was conducted by 3-point bending. Intrinsic biomechanical properties, including the ultimate stress and strain, elastic modulus, and work to failure were derived based on the structural and geometric femoral properties. Harvested femurs and vertebrae (L4) were studied for changes to bone microarchitecture by micro-computed tomography. Results Compared to the AC group (N=8), significant reductions in biomechanical determinants of bone integrity and fracture risk were found in femora of male SR rats (N=8): ultimate force (-18.3%, p< 0.017), stiffness (-13.8%, p< 0.013), and ultimate stress (-19.1%, p< 0.041). Microarchitectural changes in the L4 vertebra of SR rats included decreases in bone mineral density, bone volume/total volume, and trabecular thickness (-4%, -6%, and -5% respectively, all p< 0.008) and a tendency for decreased trabecular number (-5%, p< 0.07). Conclusion Chronic sleep restriction results in reduced vertebral bone quality and decreased femoral integrity during mature adulthood in male rats. These are clinically important sites for fracture risk and surgical recovery in human aging. Support (if any) NIH/NIA, AG083653