Bone Turnover Markers After Sleep Restriction and Circadian Disruption: A Mechanism for Sleep-Related Bone Loss in Humans

Context: Sleep abnormalities are associated with low bone mineral density. Underlying mechanisms are unknown. Objective: Investigate the impact of sleep restriction with circadian disruption on bone biomarkers. Design: Intervention study. Participants and Methods: Four bone biomarkers [C-terminal cross-linked telopeptide of type I collagen (CTX) = bone resorption, N-terminal propeptide of type I procollagen (P1NP) = bone formation, sclerostin and fibroblast growth factor 23 = osteocyte function] were measured in bihourly serum samples over 24 hours at baseline and after similar to 3 weeks of sleep restriction (5.6 hours sleep/24 hours) with concurrent circadian disruption (recurring 28-hour day in dim light) in 10 men (age groups: 20 to 27 years, n = 6; 55 to 65 years, n = 4). The effects of sleep/circadian disruption and age on bone biomarker levels were evaluated using maximum likelihood estimation in a mixed model for repeated measures. Results: P1NP levels were lower after intervention compared with baseline (P < 0.001); the decrease in P1NP was greater for younger compared with older men (28.0% vs 18.2%, P < 0.001). There was no change in CTX (Delta = 0.03 +/- 0.02 ng/mL, P = 0.10). Sclerostin levels were higher postintervention in the younger men only (Delta = 22.9% or 5.64 6 +/- 1.10 pmol/L, P < 0.001). Conclusions: These data suggest that 3 weeks of circadian disruption with concurrent sleep restriction can lead to an uncoupling of bone turnover wherein bone formation is decreased but bone resorption is unchanged. Circadian disruption and sleep restriction may be most detrimental to bone in early adulthood.