Sleep Regularity as a Potentially Modifiable Factor for Osteoporosis Prevention: Interaction With Genetic...

Sleep regularity may represent a modifiable risk factor affecting osteoporosis susceptibility, but epidemiological evidence remains scarce. This research sought to analyze the link between sleep regularity parameters and incident osteoporosis, its interaction with genetic risk, and the potential for improved sleep regularity to mitigate risk in individuals with different genetic predispositions within a population-based cohort. A longitudinal analysis was conducted using data from the UK Biobank, which included 87,231 participants without osteoporosis at the time of accelerometer data collection in 2013-2015, with follow-up until June 30, 2023. Sleep regularity parameters were determined by calculating the within-person standard deviation (SD) of 7-day accelerometer-tracked sleep parameters (including sleep duration, onset time, wake-up time, and midpoint). We investigated the association between these four sleep regularity parameters and osteoporosis risk, and assessed the potential reduction of osteoporosis occurrence by enhancing sleep regularity. Additionally, subgroup and sensitivity analyses were executed. Across a median follow-up period of 8.6 years, 2035 new osteoporosis cases were recorded. Participants in the top quartile of SD for sleep duration, onset time, and midpoint had higher osteoporosis risk compared to those in the bottom quartile (fully adjusted HRs ranged from 1.17 to 1.21). Sleep duration SD showed the highest population attributable fraction (PAF). Moreover, a statistically significant additive gene-sleep interaction was identified. When considering both sleep regularity and osteoporosis polygenic risk score (PRS), the group with the highest risk nearly doubled their osteoporosis risk compared to the group with the lowest risk (fully adjusted HRs ranged from 2.22 to 2.24). Importantly, improving sleep regularity mitigated the PRS effect on osteoporosis, with the greatest absolute risk reduction observed in individuals with intermediate PRS-1.6 to 1.7 times that of those with high PRS. Irregular sleep patterns were associated with an increased risk of developing osteoporosis, with exploratory analyses suggesting potential variation across levels of genetic susceptibility. These findings underscore the potential importance of maintaining stable sleep patterns for bone health and suggest that sleep regularity may represent a modifiable behavioral factor for osteoporosis prevention, warranting further investigation.