Association of multidimensional biomarkers of immune, nutritional, inflammatory, and metabolic status with postoperative outcomes in older hip fracture patients: a systematic review and meta-analysis

Abstract

Background The high mortality and disability rates following hip fractures in the elderly have attracted widespread attention. Underlying inflammatory, immunological, nutritional, and metabolic imbalances are major contributing factors. However, the prognostic value of multidimensional composite biomarkers encompassing these dimensions remains unclear. This systematic review aimed to evaluate the prognostic value of these composite biomarkers for postoperative outcomes in elderly patients with hip fractures. Methods A systematic search was conducted in PubMed, Web of Science, Embase, Scopus, the Cochrane Library, ProQuest, and ClinicalTrials.gov, with a cutoff date of 7 January 2026, to identify eligible cohort studies. Data were analyzed using random-effects models for both continuous and cutoff-based categorical variables. Sensitivity analyses were conducted using the modified Knapp-Hartung method with an ad hoc variance correction and a Bayesian hierarchical model. The quality of the evidence was assessed using the GRADE criteria. Results A meta-analysis was conducted, incorporating 46 cohort studies involving a total of 28,605 patients. The results showed that baseline immune-inflammatory, nutritional, and metabolic imbalances are associated with the risk of adverse postoperative outcomes. For short-term outcomes, among binary biomarkers, a low prognostic nutritional index (OR = 3.29, 95% CI: 2.22–4.88), a high neutrophil-to-lymphocyte ratio (OR = 5.17, 95% CI: 2.99–8.92), and a high glucose-to-albumin ratio (OR = 2.31, 95% CI: 1.86–2.88) constituted the core risk prognostic indicators. In the analysis of continuous variables, the prognostic nutritional index (OR = 1.09, 95% CI: 1.04–1.15), the C-reactive protein to albumin ratio (OR = 1.33, 95% CI: 1.19–1.47), and the neutrophil-to-lymphocyte ratio (OR = 1.08, 95% CI: 1.03–1.13) were also associated with an increased short-term risk. Among binary biomarkers evaluating the prognosis of medium-to-long-term adverse outcomes, in addition to the C-reactive protein to albumin ratio (OR = 3.19, 95% CI: 2.20–4.62) and the systemic immune-inflammation index (HR = 2.00, 95% CI: 1.37–2.91), the geriatric nutritional risk index (OR = 2.95, 95% CI: 1.94–4.48) also demonstrated medium-to-long-term prognostic value. Conclusion Overall, composite biomarkers of immunity, inflammation, nutrition, and metabolism demonstrate prognostic associations with short-term and medium-to-long-term adverse outcomes in older patients with hip fractures, with core prognostic indicators predominantly supported by moderate- to high-certainty evidence. These findings support the use of these multidimensional indicators as accessible and reliable assessment tools to assist clinicians in personalized perioperative risk screening and precision management.