Association between Chronic Inflammation and Poorer Long-term Functional Recovery Post-Hip Fracture in and between Men and Women

Abstract Mechanisms underlying functional recovery after hip fracture have not been widely studied in either sex, but particularly not in men. Cytokines, or biomarkers of inflammation in the blood, are associated with declines in function post hip fracture in women. Therefore, the aim of this study was to examine chronic systemic inflammation, as measured by cytokines, and their association to function and functional recovery post-hospitalization within and between the sexes. In the sample, with equal proportions of men and women, cytokines were measured at baseline, 2, 6 and 12 months post-hip fracture, including IL1-ra, IL-6 and sTNFα-R1 levels. Short Physical Performance Battery (SPPB) was measured at 2 and 6 months. Participants were divided into tertiles based on their 2-month cytokine levels. Longitudinal regression models were used to examine the change in cytokines levels over the year by sex, and to model the association of cytokine tertiles and physical function. Older adults (n=311, 50% men, age 80.9 ± 7.5 yrs.) were included. Men had higher levels of IL-6 and sTNFα-R1 at 2, 6 and 12 months. Lower 2-month cytokine levels were associated with better function at 2 months and better recovery of function at 6-months. Women in the lowest tertile of IL-6 and sTNFα-R1 at 2 months had higher SPPB scores (all p≤0.03) than men in the middle and upper tertile and these findings persisted at 6 months. Furthermore, women in the lowest tertile of IL1-ra had better recovery in the SPPB than men in all tertiles at 6 months (p≤0.03). Lower levels of systemic inflammation were associated with better functional performance at 2 months and functional recovery at 6 months post hip fracture. Observed sex differences suggest that medical management and rehabilitation strategies may need to be adapted by sex and with attention to specific inflammatory biomarkers.