The Relationships between Depressive Symptoms, Inflammatory Cytokines, and Lower Extremity Function after Hip Fracture

Abstract

Background: Hip fractures are associated with alterations in physical, psychological, and immunologic functions in more than 1.6 million older adults who are affected annually. We aimed to examine the inter-relationships between these functional domains in a sample of older adult female hip fracture patients. Methods: Participants were community-dwelling women aged >65 years, admitted to one of three Baltimore-area hospitals with a new, non-pathological fracture of the proximal femur. At baseline, 2, 6 and 12 months post-fracture, depressive symptoms were assessed with the 15-item Geriatric Depression Scale (GDS). At 2, 6, and 12 months post-fracture, serum was analyzed for interleukin-6 (IL-6) and soluble tumor necrosis factor alpha receptor 1 (sTNF-αR1), and lower extremity performance was measured by the Lower Extremity Gain Scale (LEGS). Generalized estimating equations were used to model the longitudinal relationships between variables of interest. Results: Clinically significant levels of depressive symptoms were present in 12.5% of study participants at baseline. Persistently high depressive symptoms were significantly associated with lower sTNF-αR1 levels at 2 months (p=0.02) followed by an increase in sTNF-αR1 levels by 12 months (p<0.0001). Participants in the highest categories of IL-6 (≥5.14 pg/mL) and sTNF-αR1 (≥2421 pg/mL) had the highest GDS scores in the year post-fracture (p=0.09 for both). At 12 months post-fracture, the highest IL-6 and sTNF-αR1 categories had GDS scores that were on average 1.9 (95% confidence interval [CI]: 0.4, 3.4; p=0.01) and 1.4 (95% CI: -0.1, 3.0; p=0.07) points higher than the lowest category, respectively. Participants in the highest categories of IL-6 (≥3.69 pg/mL) and sTNF-αR1 (≥2210 pg/mL) had the lowest LEGS scores in the year post-fracture (p=0.03 for IL-6; p=0.23 for sTNF-αR1). At 2 months post-fracture, the highest IL-6 and sTNF-αR1 categories had LEGS scores that were on average 4.8 (95% CI: -8.1, -1.6; p=0.004) and 3.0 (95% CI: -6.3, 0.3; p=0.07) points lower than the lowest category, respectively. Conclusions: Results from this study support a role for inflammation in the pathophysiology of depressive symptoms after hip fracture. The magnitude and speed of recovery of lower extremity function may depend on the level of the pro-inflammatory cytokine response.