Sleep and circadian disruptions negatively impact many biological systems and may represent novel, modifiable risk factors for low bone mass and fracture. We were the first to report that cumulative sleep restriction with concurrent circadian disruption (akin to rotating shift work) suppressed a marker of bone formation but not resorption in healthy men. These data parallel those from sleep restriction studies in animals where lower bone mineral density (BMD) compared to controls was also observed. This uncoupling of bone turnover markers (BTMs) in humans may limit attainment of peak bone mass if sleep and circadian disruption occur in adolescence or early adulthood during bone modeling and consolidation, and may accelerate bone loss when experienced later (e.g. during the menopausal transition, when sleep disturbance is common). My K23 data have demonstrated that combined sleep restriction and circadian disruption induce similar BTM changes in women and that these changes occur within a few days of exposure to the combined sleep and circadian disturbance. The effects of insufficient sleep duration, without extreme circadian disruption, on BTMs, independent of the inpatient laboratory environment and inherent physical inactivity, and the ability to reverse or improve BTM impairments with recovery sleep are unknown. The overall scientific objectives of this R03 application are to evaluate the effects of insufficient sleep duration, without extreme circadian disruption, on BTMs in women and men, independent of physical inactivity, and the role of recovery sleep to stabilize BTMs or compensate for the period of shortened sleep. The central hypothesis is that insufficient sleep duration, independent of relative physical inactivity, will impair a marker of bone formation (P1NP) in women and men with no change in a marker of bone resorption (CTX), and that extending sleep duration will restore P1NP levels to baseline. These novel pilot data will provide a critical extension to my K23 to generate innovative hypotheses with significant clinical impact that I can test in my R01 - a comprehensive investigation of the mechanisms by which sleep and circadian disruption alter bone health in humans.
The specific aims are: 1. Investigate if insufficient sleep duration during the work week decreases a marker of bone formation without altering a bone resorption marker. 2. Establish that insufficient sleep induces changes in bone biomarkers independent of physical inactivity inherent in an inpatient lab study, by comparing BTM changes in sleep-restricted participants to controls. 3. Determine if extending sleep for a weekend or 3 weeks can improve or reverse impairments in bone metabolism induced by sleep restriction. This research will have a sustained and powerful influence on science and patient care because it can introduce a paradigm shift in osteoporosis prevention, evaluation, and treatment.
Our work suggests combined sleep restriction and circadian disruption suppresses a marker of bone formation but not resorption - an imbalance that could lead to bone loss, osteoporosis, and increased fracture risk. This application will address knowledge gaps by investigating if sleep restriction, independent of extreme circadian disruption and the inpatient laboratory environment (e.g., changes in usual physical activity), similarly impairs bone metabolism, and the role of recovery sleep to stabilize or compensate for the period of shortened sleep. If the proposed hypotheses are supported and insufficient sleep duration is recognized as a novel risk factor for low bone mineral density, it will introduce a paradigm shift in the prevention, evaluation and treatment of osteoporosis.