Molecular Predictors of Mortality in Frail Patients With Hip Fractures

Purpose: Inflammatory burden in hip fracture has been poorly investigated. Cytokines such as CRP, IL-10 IL-6 and TNF-alpha have been shown to play a role in predicting complications and mortality. Many studies have only investigated a few different types of inflammatory proteins. We aimed to identify molecular inflammatory predictors of mortality in frail patients who have sustained fragility hip fractures utilizing proteomic analysis. This method allows us to measure 92 target inflammatory proteins with increased specificity through proximity extension assays.

Methods: From the Functioning of Elder Muscle Understanding Recovery (FEMUR) study (IRAS:268635) 59 patients were studied. These patients were aged >65 years old with a clinical frailty score of ≥4 and presented with a fragility hip fracture. Routine audit personnel prospectively completed the Standardised Audit of Hip Fracture of Europe (SAHFE) form including the following outcomes 6-month mortality and development of at least one post operative complication. O-link Proteome biomarker analysis was undertaken from serum samples obtained at the time of anaesthetic prior to surgery. Statistical analysis included Spearmans correlation, Kaplan-Meier survival and receiver operator characteristic curve analysis.

Results: In patients with hip fracture, 4 proteins were significantly correlated with the development of post operative complications Six proteins were significantly correlated with frailty and 13 proteins significantly associated with 6-month survival. With FGF-23 being the most significantly correlated(p <.001). We also demonstrate elevated levels of FGF-23 in patients who are severely frail have very poor survival as demonstrated by Kaplan-Meier and Receiver operator curve analysis FGF-23 and clinical frailty scale score 7 AUC 0.828 (95%CI 0.709 to 0.946).

Conclusion: To our knowledge this is the first study to investigate a range of molecular inflammatory markers using proteomic analysis in patients with fragility hip fractures and their relationship with mortality. We have highlighted several potential biomarkers of mortality which may help guide therapeutic treatments and provide prognostic information. Further work is underway to identify molecular markers of frailty and their correlation with frailty outcomes.