Christine M Swanson1,2, Steven A Shea3,4,5, Pamela Wolfe6, Sean W Cain4,7,8, Mirjam Munch9, Nina Vujovic4,7, Charles A Czeisler4,7, Orfeu M Buxton4,7,10,11, Eric S Orwoll1. 1. Division of Endocrinology and Bone and Mineral Unit, Oregon Health & Science University, Portland, Oregon 97239. 2. Division of Endocrinology, University of Colorado, Aurora, Colorado 80045. 3. Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, Oregon 97239. 4. Sleep Health Institute, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts 02115. 5. Oregon Health & Science University and Portland State University School of Public Health, Portland, Oregon 97239. 6. Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045. 7. Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts 02115. 8. Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Clayton, Victoria 3800, Australia. 9. Charité University Medicine Berlin, Institute of Physiology, 10117 Berlin, Germany. 10. Department of Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania 16802. 11. Department of Social and Behavioral Sciences, Harvard Chan School of Public Health, Boston, Massachusetts 02115.
Abstract
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 ∼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 (Δ = 0.03 ± 0.02 ng/mL, P = 0.10). Sclerostin levels were higher postintervention in the younger men only (Δ = 22.9% or 5.64 ± 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.
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 ∼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 (Δ = 0.03 ± 0.02 ng/mL, P = 0.10). Sclerostin levels were higher postintervention in the younger men only (Δ = 22.9% or 5.64 ± 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.
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