AS589 - Nocturnal Hypoxia, Sleep and Fractures and Falls: WHI and MrOS

Investigator Names and Contact Information

Jane Cauley (jcauley@pitt.edu)

Carolyn Crandall

Introduction/Intent

The long-term goal of the project is to describe the association between sleep disturbances including nocturnal hypoxemia, sleep duration, sleep fragmentation, insomnia and sleep quality 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 in both older men and women through several underlying mechanisms including hypoxia, inflammation, poor muscle strength and poor physical functioning.

This proposal builds on two large observational studies that have enrolled well characterized cohorts of older men and women: WHISPER: Women’s Health Initiative (WHI) Sleep Hypoxia Effect on Resilience and the Osteoporotic Fractures in Men Sleep Study (MrOS Sleep). WHISPER is an observational study of sleep disorders and intermittent hypoxia and their relationship to cardiovascular disease (CVD), cancer and cognitive impairment. WHISPER capitalizes on the unique and rich resources of the WHI that provide solid infrastructure and an extensive data repository to answer key questions about poor sleep and important health outcomes. WHISPER will enroll 5000 WHI participants into a sleep study in which overnight pulse oximetry and 4-day wrist actigraphy will be collected; these women will be followed for CVD, cancer and cognitive function outcomes. 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 whether the associations between poor sleep and subsequent risk of falls and fractures differ by sex. In the MrOS sleep study, 3135 men participated in a comprehensive sleep assessment including 7-day wrist actigraphy and in home polysomnography including overnight oximetry with follow-up for incident fractures and falls.

Sleep disturbances are common in the US with up to 60% of older adults with sleep-disordered breathing (SDB). Intermittent hypoxia is the hallmark of obstructive sleep apnea and in addition to CVD consequences, it has been linked to poor physical function. We demonstrated in MrOS that men with >10% or more of sleep time at arterial oxygen saturation (SaO₂) of less than 90% had a greater risk of one or more falls (relative risk (RR)=1.25; 95% confidence interval (CI), 1.04-1.51) and two or more falls, RR=1.43; 95% CI, 1.06-1.92) than those with <10% of sleep time with less than 90% arterial SaO₂. Men with increasing nocturnal desaturation also had a 30-40% increased risk of non-spine fractures compared to men with normal nocturnal SaO₂. These findings were independent of SDB and suggest that greater sleep time at lower SaO2 maybe a mechanism linking sleep disorders to falls and fractures. We now propose to study these associations in older women.
We propose the following specific aims:

Aim 1: WHISPER

• A. Primary: Test the hypothesis that increased SDB-related intermittent hypoxemia, as measured by elevated oxygen desaturation index (ODI) is associated with recurrent falls.
• B. Secondary: Test the hypothesis that short or long sleep duration and greater sleep fragmentation (based on actigraphy), a greater insomnia index and overall poor sleep quality are associated with increased risk of recurrent falls during an average of 3-years of follow-up.

Aim 2: WHISPER

• A. Primary: To test the hypothesis that increased SDB related intermittent hypoxemia, as measured by elevated ODI is associated with an increased risk of incident adjudicated clinical fractures, and specifically, major osteoporotic fractures (hip, wrist, spine and humerus) during an average follow-up of 3-years.
• B. Secondary: Test the hypothesis that short or long sleep duration, greater sleep fragmentation and a greater insomnia index and overall poor sleep quality are associated with an increased risk of incident adjudicated clinical fractures and specifically, major osteoporotic fractures.

Aim 3: WHISPER and MrOS

• A. Primary: Because the growing emphasis on the influence of sex on biological outcomes in parallel analyses, we will explore whether results in women (WHISPER) and men (MrOS) regarding the associations between sleep disorders and fractures and falls are similar.

Extending sleep studies to include falls and fracture is important because falls and fractures have major public health impact. Interventions aimed at decreasing nocturnal hypoxia may decrease falls and fractures. Our proposal offers a cost-efficient opportunity to investigate whether sleep disturbances influence fall and fracture risk in both older men and women. The WHI leadership (Ancillary Study Committee, Data Safety Monitoring Board and Steering Committee) enthusiastically support the extension of WHISPER to include important musculoskeletal outcomes (see letter of support).