Abstract

Bone turnover markers (BTMs) display diurnal rhythms. Studies in rats and men suggest sleep restriction and circadian disruption are detrimental to bone metabolism. The effects of sleep and circadian disruption on BTMs in women are unknown. We hypothesized that cumulative sleep restriction and concurrent circadian disruption would decrease P1NP levels in women and that the magnitude of decline would be greater in younger compared to older women, as previously reported in men (JCEM 102(10) 2017). Four bone biomarkers (P1NP and osteocalcin = bone formation; C-telopeptide (CTX) = bone resorption; sclerostin = osteocyte protein/bone formation inhibitor) were measured in nine women from bihourly samples over 24h at baseline and after ~3 weeks of sleep restriction (~5.6h sleep/24h) with concurrent circadian disruption (recurring 28-h ‘day’ in dim light), termed SRCD. Maximum likelihood estimation in a repeated measures model was used to assess the effects of SRCD and age on bone biomarkers. A cosinor model was used to estimate circadian rhythm. Data are presented as estimate ± SEE. Five women were younger (avg 22 yrs, range 18-24) and four were older (avg 58 yrs, range 56-60). Baseline bone biomarker levels did not differ significantly by age (all p > 0.07) and were 51.6 ± 4.3 μg/L (P1NP), 0.686 ± 0.042 ng/mL (CTX), 21.8 ± 1.4 ng/mL (osteocalcin) and 20.5 ± 1.1 pmol/L (sclerostin). CTX was the only biomarker with a significant diurnal rhythm (p < 0.001). The average ± SD duration of SRCD exposure was 22 ± 2 calendar days. P1NP was significantly lower after SRCD in the group (Δ = -17.9% or -9.2 ± 2.8 μg/L, p = 0.02) and in the younger women (Δ = -22.3% or -12.5 ± 3.7 μg/L, p = 0.01). For the group, SRCD had no significant effect on CTX (Δ = 9.1% or 0.063 ± 0.052 ng/mL, p = 0.27), sclerostin (Δ = 15.9% or 3.3 ± 1.5 pmol/L, p = 0.07), or osteocalcin (Δ = -9.4% or -2.1 ± 0.9 ng/mL, p = 0.06); whereas after SRCD, CTX was significantly higher in younger women (Δ = 33.0% or 0.182 ± 0.069 ng/mL, p = 0.04) and sclerostin was significantly higher in older women (Δ = 24.9% or 5.4 ± 2.2 pmol/L, p = 0.05). The small sample size precludes definitive conclusions, particularly regarding age effects. Environmental differences compared to home (e.g., diet, activity) may have also contributed to the observed changes. However, these preliminary data suggest that cumulative sleep restriction and concurrent circadian disruption negatively altered bone metabolism in women by decreasing a marker of bone formation (P1NP) and, in younger women, also increasing a marker of bone resorption (CTX). Similar to previous findings in men, the detrimental impact of cumulative sleep restriction and concurrent circadian disruption on bone metabolism was of greater magnitude in younger women. If sustained, this pattern of BTM change may lead to bone loss and lower bone mineral density over time. Disclosures: See book Funding: K23; Center for Women’s Health Research Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

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