Lower Bone Formation after 3 Weeks of Sleep Restriction with Circadian Disruption: A Mechanism for Sleep-Related Bone Loss

Presentation Number: OR08-6
Date of Presentation: April 1st, 2017

Christine Swanson*1, Steven A Shea2, Pamela Wolfe1, Sheila Markwardt2, Charles A Czeisler3, Orfeu Marcello Buxton4 and Eric S Orwoll5
1University of Colorado, Aurora, CO, 2Oregon Health & Science University, Portland, OR, 3Brigham and Women's Hospital, Boston, MA, 4Pennsylvania State University, University Park, PA, 5Oregon Health & Sciences Univ, Portland, OR


Long and short sleep durations have both been associated with low BMD, but underlying mechanisms are unknown. We investigated the impact of combined circadian disruption with sleep loss, akin to the stresses endured during rotating shift work, on biomarkers of bone metabolism in 10 healthy men (age groups: 20-27y, n = 6; 55-65yo, n = 4). We hypothesized that sleep/circadian disturbance would negatively alter bone balance.

Four bone biomarkers (CTX = bone resorption; PINP = bone formation; sclerostin/FGF-23 = osteocyte function) were measured on q2h plasma samples over a 24-h interval at baseline and after a 3-wk intervention of sleep restriction (5.6h sleep/24-h) with concurrent circadian disruption (recurring 28-h ‘day’). Post-intervention samples were obtained when participants were at a similar circadian phase compared to the baseline samples.

Maximum likelihood estimates for repeated measures were obtained to assess the effects of sleep/circadian disruption and of age, on bone biomarker levels across a 24-h interval.

Except FGF-23, bone biomarker levels varied significantly by age at baseline (CTX/PINP higher in younger men (p = 0.01 and 0.02, respectively); sclerostin higher in older men (p = 0.005). This is consistent with higher bone (re)modeling rates in younger men during their consolidation phase and a nadir in BTMs in 50-60yo men. PINP levels were significantly lower post intervention compared to baseline; the decrease in PINP occurred at every time point and this decline was greater for the younger men with higher bone turnover at baseline (-27% or -20.73 ± 1.38 mcg/L, p<0.001), compared to older men (-18% or -10.01 ± 1.70 mcg/L, p<0.001). These decreases were of similar magnitude to the early increase seen with teriparatide treatment and occurred independently of changes in CTX (Δ = 2-4%, p = 0.56). Sclerostin levels were significantly higher post-intervention in the younger men only (Δ +25% or 5.92 ± 1.84 pmol/L, p=0.002) compared to older men (Δ +2.3% or 0.90 ± 2.26 pmol/L, p=0.69). Post intervention, FGF-23 levels were 6.5% lower (-2.46 ± 0.96 pg/mL; p = 0.01).

These results suggest that 3 weeks of sleep loss with circadian disruption can lead to an uncoupling of bone turnover and a potential “catabolic window,” wherein bone formation is decreased but bone resorption is unchanged. These data further suggest that sleep disruption may be most detrimental to bone during high bone turnover states (i.e. bone modeling, menopause). These changes could be due to direct effects on diurnal bone remodeling (either related to sleep restriction, or prior circadian disruption), indirect effects via changes in sex-hormone status, inflammation and/or sympathetic tone induced by sleep disruption, or less likely, the decreased physical activity inherent in study conditions. Further studies are needed to confirm these data independent of study conditions and to explore sex differences and mechanisms.


Disclosure: CAC: , Merck & Co., , Quest Diagnostics. Nothing to Disclose: CS, SAS, PW, SM, OMB, ESO