Impaired sleep has been linked with lower bone density and increased risk of fracture in adults. However, it is not known if sleep patterns effect gains in bone density and strength during childhood. This knowledge gap needs to be addressed because bone accretion in childhood determines peak bone mass and risk of osteoporosis in later life. The long-term goal is to determine if sleep patterns predict bone density and strength during the bone accretion years of the lifespan. The overall objective of this application is to determine if sleep patterns predict changes in bone density and strength from early-to-mid adolescence. Adolescents aged 12-13y (7th grade) will be enrolled and prospectively followed-up annually for 2-years. This age range is being investigated because this is a critical period when a large proportion of peak bone mass and strength are gained, and when sleep duration tends to decline. At each time point, bone density will be measured using dual energy X-ray absorptiometry and bone strength will be measured by high resolution peripheral quantitative computed tomography. Sleep patterns will be measured by actigraphy and self-report. DNA will be collected and genotyped because bone density and strength are complex traits and genetic susceptibility to bone fragility may modify the association between sleep patterns and bone outcomes. The central hypothesis is that impaired sleep duration, timing and quality will be associated with lesser gains in bone density and strength in adolescence, with the associations stronger for those genetically predisposed to bone fragility. This hypothesis will be tested by pursuing three specific aims: 1) Determine if sleep patterns predict changes in bone density in adolescence; 2) Elucidate if bone strength changes during adolescence are influenced by sleep patterns; and 3) Investigate the combined effect of bone fragility genetic scores and sleep patterns on bone changes during adolescence. The applicants? preliminary data among adolescents show an inverted U-shaped association between sleep duration and areal bone mineral density, and they observed that later timing of sleep onset predicted lower areal bone mineral density and lower bone strength. The investigators also demonstrated that bone fragility genetic scores associated with lower areal bone mineral density in children and adolescents, but a lifestyle factor (in this case physical activity) could help overcome the negative genetic effects. The rationale for the proposed research is the need to establish a rigorous base of epidemiological evidence supporting associations between sleep and bone outcomes, which will provide a foundation to perform intervention studies that target sleep patterns and evaluate bone accretion. The approach is innovative because sleep patterns have not yet been considered as predictors of bone mass and strength in adolescence, and advanced imaging methods will be combined with advanced growth, sleep and genetic epidemiological methods. With respect to outcomes, the investigators anticipate that they will establish sleep patterns as key predictors of bone density and strength in adolescence.

Public Health Relevance

The proposed research is relevant to public health because the prevalence of osteoporosis is excessively high and primary prevention strategies to optimize bone accretion in childhood are needed to offset the burden of this chronic disease. Emerging evidence from animal models and adults have implicated impaired sleep patterns as risk factors for bone fragility, but it is not known if sleep patterns predict bone density and strength in childhood. The project is relevant to the NICHD?s mission that ?...all children have the chance to fulfill their potential to live healthy and productive lives free from disease?, and is directly aligned with an NICHD Pediatric Growth and Nutrition Branch Research Priority: ?...understand the determinants of bone acquisition to advance lifestyle strategies to maximize peak bone mass and strength in adolescence to prevent osteoporosis.?

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
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Bremer, Andrew
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Children's Hospital of Philadelphia
United States
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