Sleep Restriction With Circadian Disruption Negatively Alter Bone Turnover Markers in Women

Abstract

Purpose: The purpose of this work is to determine whether an uncoupling of bone turnover markers (BTMs) occurs in women exposed to the combination of sleep restriction with circadian disruption (SRCD), as previously reported in men.

Methods: Four bone biomarkers (N-terminal propeptide of type I procollagen [P1NP] and osteocalcin = bone formation; C-telopeptide [CTX] = bone resorption; sclerostin = bone formation inhibitor) were measured in bihourly samples over 24 hours at baseline and after approximately 3 weeks of sleep restriction (~5.6 hours of sleep/24 hours) with concurrent circadian disruption (SRCD, recurring 28-hour "day" in dim light). Maximum likelihood estimation in a repeated-measures model was used to assess the effects of SRCD and age on bone biomarkers.

Results: Five women were young (22 ± 2.8 years) and four were older (58 ± 1.8 years). Baseline bone biomarker levels did not differ by age (all P ≥ .07). Bone formation markers were lower after SRCD (estimate ± SEE, ΔP1NP = -9.5 ± 2.8 μg/L, P = .01; Δosteocalcin = -2.3 ± 0.9 ng/mL, P = .04). The P1NP decline was greater in young women (ΔP1NP = -12.9 ± 3.7 μg/L, P = .01). After SRCD, CTX was significantly higher in young women (0.182 ± 0.069 ng/mL, P = .04) but did not change in older women.

Conclusions: These pilot data are similar to previous findings in men and suggest that SRCD negatively altered bone metabolism in women by decreasing markers of bone formation and, in young women, increasing a marker of bone resorption. If sustained, this pattern of BTM uncoupling may lead to bone loss and lower bone mineral density.

Trial registration: ClinicalTrials.gov NCT00506428.

Keywords: CTX; P1NP; bone turnover markers; circadian disruption; shift work; sleep.

© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Twenty-four–hour serum profiles of bone biomarkers at baseline and post sleep restriction with circadian disruption intervention, by age group. The X-axis represents number of hours into the 24-hour sampling profile. Data from the 5 young women are displayed in the left column and the 4 older women in the right column. Twenty-four–hour fitted profiles depicted for A, N-terminal propeptide of type I procollagen (P1NP), B, osteocalcin, C, C-telopeptide of type I collagen (CTX), and D, sclerostin at baseline (dashed light blue) and post sleep restriction with circadian disruption (SRCD) (solid purple) by age group. Raw averages (±SD) are plotted for every–2-hour samples. Sleep opportunities for the respective phases of the protocol are represented by horizontal light blue (baseline) or purple (post-SRCD) bars at the top of each graph. The SRCD protocol consisted of recurring scheduled 28-hour sleep-wake cycles (21.47-hour wake episode and a 6.53-hour sleep opportunity) that provided the equivalent of 5.6-h of sleep opportunity per 24 hours. Upside-down triangles along the x-axis represent meal times of breakfast (hour 12), lunch (hour 17), dinner (hour 22), and snack (hour 24). The 2 serum profiles were aligned by the midpoint of sleep.