Insufficient sleep, a common problem that has been linked to chronic disease risk, might also be an unrecognised risk factor for bone loss. Results of a study were presented at ENDO 2017, The Endocrine Society’s 99th annual meeting in Orlando.
The study investigators found that healthy men had reduced levels of a marker of bone formation in their blood after three weeks of cumulative sleep restriction and circadian disruption, similar to that seen in jet lag or shift work, while a biological marker of bone resorption, or breakdown, was unchanged.
“This altered bone balance creates a potential bone loss window that could lead to osteoporosis and bone fractures,” lead investigator Dr Christine Swanson, an assistant professor at the University of Colorado in Aurora, said. Swanson completed the research while she was a fellow at Oregon Health & Science University in Portland, Oregon, with Drs Eric S Orwoll and Steven A Shea.
“If chronic sleep disturbance is identified as a new risk factor for osteoporosis, it could help explain why there is no clear cause for osteoporosis in the approximately 50% of the estimated 54m Americans with low bone mass or osteoporosis,” Swanson said.
Inadequate sleep is also prevalent, affecting more than 25% of the US population occasionally and 10% frequently, the Centres for Disease Control and Prevention report.
The 10 men in this study were part of a larger study that some of Swanson’s co-authors conducted in 2012 at Brigham and Women’s Hospital in Boston. That study evaluated health consequences of sleep restriction combined with circadian disruption. Swanson defined circadian disruption as “a mismatch between your internal body clock and the environment caused by living on a shorter or longer day than 24 hours.”
Study subjects stayed in a lab, where for three weeks they went to sleep each day four hours later than the prior day, resulting in a 28-hour “day.” Swanson likened this change to “flying four time zones west every day for three weeks.” The men were allowed to sleep only 5.6 hours per 24-hour period, since short sleep is also common for night and shift workers. While awake, the men ate the same amounts of calories and nutrients throughout the study.
Blood samples were obtained at baseline and again after the three weeks of sleep manipulation for measurement of bone biomarkers. Six of the men were ages 20 to 27, and the other four were ages 55 to 65. Limited funding prevented the examination of serum from the women in this study initially, but the group plans to investigate sex differences in the sleep-bone relationship in subsequent studies.
After three weeks, all men had significantly reduced levels of a bone formation marker called P1NP compared with baseline, the researchers reported. This decline was greater for the younger men than the older men: a 27% versus 18% decrease. She added that levels of the bone resorption marker CTX remained unchanged, an indication that old bone could break down without new bone being formed.
“These data suggest that sleep disruption may be most detrimental to bone metabolism earlier in life, when bone growth and accrual are crucial for long-term skeletal health,” she said. “Further studies are needed to confirm these findings and to explore if there are differences in women.”
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.
Christine Swanson, Steven A Shea, Pamela Wolfe, Sheila Markwardt, Charles A Czeisler, Orfeu Marcello Buxton, Eric S Orwoll