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 ∼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.

[1]  S. Shea,et al.  24-hour profile of serum sclerostin and its association with bone biomarkers in men , 2017, Osteoporosis International.

[2]  G. Biolo,et al.  Markers of bone metabolism during 14 days of bed rest in young and older men , 2017, Journal of musculoskeletal & neuronal interactions.

[3]  E. Sforza,et al.  Does Subjective Sleep Affect Bone Mineral Density in Older People with Minimal Health Disorders? The PROOF Cohort. , 2016, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[4]  Liang Wang,et al.  Effects of chronic sleep deprivation on bone mass and bone metabolism in rats , 2016, Journal of Orthopaedic Surgery and Research.

[5]  Martina Heer,et al.  Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest , 2016, Journal of Bone and Mineral Metabolism.

[6]  R. Chapurlat,et al.  Are Biochemical Markers of Bone Turnover Representative of Bone Histomorphometry in 370 Postmenopausal Women? , 2015, The Journal of clinical endocrinology and metabolism.

[7]  B. Dawson-Hughes,et al.  Association between Sleep Duration, Insomnia Symptoms and Bone Mineral Density in Older Boston Puerto Rican Adults , 2015, PloS one.

[8]  Tina D Cunningham,et al.  Is Self‐Reported Sleep Duration Associated with Osteoporosis? Data from a 4‐Year Aggregated Analysis from the National Health and Nutrition Examination Survey , 2015, Journal of the American Geriatrics Society.

[9]  Y. Liang,et al.  Sleep duration and timing in relation to osteoporosis in an elderly Chinese population: a cross-sectional analysis in the Dongfeng–Tongji cohort study , 2015, Osteoporosis International.

[10]  J. Cauley,et al.  Obstructive Sleep Apnea and Metabolic Bone Disease: Insights Into the Relationship Between Bone and Sleep , 2015, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[11]  Chao Liu,et al.  The associations of bedtime, nocturnal, and daytime sleep duration with bone mineral density in pre- and post-menopausal women , 2015, Endocrine.

[12]  S. Redline,et al.  Hypoxia During Sleep and the Risk of Falls and Fractures in Older Men: The Osteoporotic Fractures in Men Sleep Study , 2014, Journal of the American Geriatrics Society.

[13]  J. Staab,et al.  Bone formation is suppressed with multi-stressor military training , 2014, European Journal of Applied Physiology.

[14]  G. Ning,et al.  Associations between sleep duration, daytime nap duration, and osteoporosis vary by sex, menopause, and sleep quality. , 2014, The Journal of clinical endocrinology and metabolism.

[15]  J. M. Harris,et al.  PINP as a biological response marker during teriparatide treatment for osteoporosis , 2014, Osteoporosis International.

[16]  S. Khosla,et al.  Effects of age on bone mRNA levels of sclerostin and other genes relevant to bone metabolism in humans. , 2014, Bone.

[17]  S. Hulley,et al.  Designing clinical research , 2013 .

[18]  D. Kiel,et al.  Repeat bone mineral density screening and prediction of hip and major osteoporotic fracture. , 2013, JAMA.

[19]  P. Zysset,et al.  Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis , 2013, Osteoporosis International.

[20]  B. Clarke,et al.  Clinical utility of serum sclerostin measurements. , 2013, BoneKEy reports.

[21]  D. Bauer,et al.  Chapter 67 – Biochemical Markers of Bone Turnover in Osteoporosis , 2013 .

[22]  J. Toth,et al.  Chronically inadequate sleep results in abnormal bone formation and abnormal bone marrow in rats , 2012, Experimental biology and medicine.

[23]  S. Shea,et al.  Adverse Metabolic Consequences in Humans of Prolonged Sleep Restriction Combined with Circadian Disruption , 2012, Science Translational Medicine.

[24]  Céline Vetter,et al.  Social jetlag and obesity. , 2012, Current biology : CB.

[25]  T. Fukui,et al.  Association between osteoporosis and sleep duration in healthy middle-aged and elderly adults: a large-scale, cross-sectional study in Japan , 2012, Sleep and Breathing.

[26]  F. Jiang,et al.  Association between sleep duration and bone mineral density in Chinese women. , 2011, Bone.

[27]  J. Krege,et al.  PINP as an aid for monitoring patients treated with teriparatide. , 2011, Bone.

[28]  S. Hankinson,et al.  Nightshift work and fracture risk: the Nurses’ Health Study , 2009, Osteoporosis International.

[29]  C. Milgrom,et al.  How stress fracture incidence was lowered in the Israeli army: a 25-yr struggle. , 2008, Medicine and science in sports and exercise.

[30]  P. Garnero,et al.  Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. , 2008, Clinical chemistry.

[31]  S. Cummings,et al.  Inflammatory Markers and Incident Fracture Risk in Older Men and Women: The Health Aging and Body Composition Study , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  A. Leblanc,et al.  Skeletal responses to space flight and the bed rest analog: a review. , 2007, Journal of musculoskeletal & neuronal interactions.

[33]  J. Reginster,et al.  Development of an algorithm for using PINP to monitor treatment of patients with teriparatide* , 2006, Current medical research and opinion.

[34]  Nader Rifai,et al.  Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. , 2004, Journal of the American College of Cardiology.

[35]  C. Christiansen,et al.  Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting. , 2002, Bone.

[36]  M. Inaba,et al.  Clinical evaluation of the Elecsys beta-CrossLaps serum assay, a new assay for degradation products of type I collagen C-tlopeptides. , 2001, Clinical chemistry.

[37]  Derk-Jan Dijk,et al.  Paradoxical timing of the circadian rhythm of sleep propensity serves to consolidate sleep and wakefulness in humans , 1994, Neuroscience Letters.