Examining Post-Hip Fracture Characteristics to Explain Sex Differences in Short- and Long-term Hip Fracture Mortality

Abstract

Men die at a higher rate than women up to two years after a hip fracture. Moreover, the number of hip fractures among men is expected to increase over the next 30 years with potential sex differences in long-term trajectories of recovery. Therefore, Aim 1 assessed whether male sex was a significant risk factor of all-cause and infection-specific mortality after hip fracture; Aim 2 determined if sex moderated the association between physical performance at 2 months post-fracture and mortality; and Aim 3 evaluated the mediating role of depressive symptoms (at 2 months post-fracture) on the association between TNFα-R1-R1 and mortality and if sex moderated the inflammation-depressive symptoms-mortality link. Data were from the Baltimore Hip Studies (BHS) 7th cohort (168 men,171 women) that recruited participants in eight hospitals within the BHS network. Women were frequency-matched (1:1) to men on timing of admission. Cox proportional hazard models evaluated associations between sex and mortality (Aim 1) and the moderating effect of sex between physical performance measures and mortality (Aim 2). An Aalen additive hazard model was created and later stratified by sex to assess the mediating effect of depressive symptoms in the association of TNFα-R1 with mortality (Aim 3). Participants were average age of 80 years and the median mortality follow-up was 4.9 (Interquartile Range=2.3-8.7) years. Men had significantly higher all-cause [Hazard Ratio (HR)=2.31, 95% confidence interval (CI) 2.02-2.59] and infection-specific [HR=4.43, 95% CI 2.07-9.51] mortality. One-unit higher on each physical performance measure was associated with lower mortality [SPPB (HR=0.91, CI=0.83-0.98); gait speed (in 0.1 meters/second) (HR=0.98, CI=0.97-0.99); and grip strength (in kg) (HR=0.95, CI=0.93-0.98)], but the associations did not differ by sex. TNFα-R1 had stronger association with mortality among men compared to women; there were 161 (95%, CI=36-286) and 16 (95%, CI=-58-89) additional deaths in men and women per 1,000 person-years, respectively in the 3rd TNFα-R1 tertile compared to the 1st tertile. However, depressive symptoms did not mediate the association between TNFα-R1 and all-cause mortality in either sex. Results show higher long-term mortality in men and that infection and elevated acute TNFα-R1 levels may play a role in the sex difference.