Sleep, Falls and Fractures in men and women: Role of nocturnal hypoxia

One in three women and one in five men age ≥50 years will experience an osteoporotic fracture in their
lifetime. Falls are common with 25% of older adults reporting ≥1 fall and 12-15% reporting ≥2 falls annually
with costs to Medicare in 2015 of $31 billion. More recently, fall death rates in the US have steadily increased.
Therefore, identifying modifiable risk factors for falls and fractures is essential. Sleep disturbances are
common in the US with up to 60% of older adults meeting criteria for sleep-disordered breathing (SDB).
Intermittent hypoxemia (IH) is the hallmark of obstructive sleep apnea. The long-term goal of the project is to
describe the prospective association between sleep disturbances including objective measures of IH, SDB,
sleep duration, sleep efficiency and disrupted circadian rest-activity rhythms and incident fractures and
recurrent falls in older women and men. The scientific premise is that poor sleep increases the risk of falls
and fractures through several mechanisms including IH and SDB. This proposal builds on two large well-
characterized studies that enrolled older men and women: WHISPER: Women’s Health Initiative (WHI) Sleep
Hypoxia Effect on Resilience, and the Outcomes of Sleep Disorders in Older Men Study (MrOS Sleep Study).
WHISPER is an observational study of sleep disorders and their relationship to cardiovascular disease, cancer
and cognitive impairment. WHISPER recruited 4959 WHI participants for in home sleep testing (including
oximetry and SDB assessment) and 6-day wrist actigraphy. We propose to extend WHISPER to include the
important clinical and geriatric outcomes of recurrent falls and fractures. We also propose to capitalize
on the existing data from the MrOS Sleep Study to provide comparable data on men to test whether the
associations between poor sleep and risk of falls and fractures differ by sex. In the MrOS Sleep Study, 2865
men participated in a sleep assessment including wrist actigraphy and in-home polysomnography with
overnight oximetry. We demonstrated that nocturnal hypoxemia is associated with greater risk of recurrent
falls and non-spine fractures in older men. However, there are no studies of comprehensive sleep measures
including IH and falls and fractures in older women despite established sex differences in sleep disorders and
fractures. We will test the hypotheses that IH as measured by % sleep time oxygen saturation (SaO2) <90%
and SDB will be associated with an increased risk of recurrent falls (Aim 1) and fractures (Aim 2) independent
of sleep fragmentation. Secondary aims will test the hypotheses that short or long sleep duration, sleep
efficiency and fragmentation and disrupted circadian rhythms, (all from actigraphy) are also associated with
recurrent falls (Aim 1) and fractures (Aim 2) and these associations are independent of IH. Finally, we will
perform parallel analyses in men to explore sex differences (Aim 3). Extending WHISPER to include falls and
fractures is a cost-efficient opportunity to substantially increase our understating of the impact of sleep on the
health of older adults.

Grant Number: 5R01AG071592-04
NIH Institute/Center: NIH
Principal Investigator: JANE CAULEY