Systemic immune-inflammation index to albumin (SII/ALB) ratio as a novel dual-dimensional powerful predictor for hip fractures in elderly females with diabetes: a postmenopausal longitudinal cohort study.

Purpose: Hip fracture is the most dangerous and potentially lethal fracture, described as "the last fracture of life" in older adults. Previous studies have shown that excessive immunoinflammatory response and nutrient deficiency may be involved. Nevertheless, a predictor for hip fracture risk that combines a thorough evaluation of immunoinflammatory with malnutritional conditions in postmenopausal women with type 2 diabetes mellitus (T2DM) remains scarce. This study explored the relationship between the SII/ALB ratio (SAR) and fragility fracture risk in postmenopausal older adults with T2DM.

Methods: Between January 2014 and January 2021, a total of 509 postmenopausal female participants with T2DM were recruited from the Medical Record Database of the People's Hospital of Guangxi Zhuang Autonomous Region. Finally, 363 participants with an age median of 69.00 (64.00-75.00), were eligible for inclusion in this analysis. According to the statistical tertiles of the SAR, all participants were split into three groups: low-level (≤ 98.24, n = 121), moderate-level (98.24-157.25, n = 121), and high-level (≥ 157.25, n = 121). The participants were followed up for seven years, with a median follow-up time of 45.9 months (1389 person-years). The relationships between the SAR and a real-world fragility fracture event and an individualized future 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) calculated by the fracture risk assessment tool (FRAX) were evaluated through Spearman's partial correlation analysis, restricted cubic spline (RCS) model, Cox proportional hazards regression model, and Kaplan-Meier survival analysis. Furthermore, some indicators such as geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and SII were also calculated and compared to their diagnostic efficacy and the clinical application value through the receiver operating characteristic (ROC) curve analysis and the decision curve analysis (DCA), respectively.

Results: Of the 363 participants, 69 suffered a real-world fragility fracture event (19%). Spearman's partial correlation analysis indicated that SAR was negatively related to femoral neck (FN) bone mineral density (BMD) (r = -0.108, P = 0.041) and total hip (TH) BMD (r = -0.118, P = 0.025), but not lumbar spine (LS) BMD (all Models P > 0.05); positively correlated with an individualized future 10-year probability of MOF (r = 0.136, P = 0.010) and HF (r = 0.139, P = 0.008) calculated by FRAX, especially in hip fracture risk. The RCS model demonstrated the relationship between the SAR and a fragility fracture endpoint event in a J-shaped dose-dependent manner (P for overall < 0.001, P for nonlinear = 0.866). Multivariate Cox regression analysis indicated that the SAR was positively associated with fragility fracture risk (P < 0.001). Kaplan-Meier survival analysis showed that patients with higher levels of SAR had a greater probability of fragility fracture risk (log-rank, P < 0.0001). The ROC curve demonstrated an optimal SAR cut-off value of 146.209 with an area under the curve (AUC) of 0.740, a sensitivity of 0.681, and a specificity of 0.701 (P < 0.001). According to the AUC values, the ROC curve analysis combined with the DCA illustrated that the diagnostic efficacy and the clinical application benefit ranked as follows: SAR > SII > PNI > GNRI, respectively.

Conclusion: Our findings show the SAR is a novel dual-dimensional powerful predictor for fragility fracture risk, especially hip fracture, and as an effective tool for developing fragility fracture prevention strategies in postmenopausal females with T2DM. Consequently, monitoring SAR levels in usual clinical practice to focus on immunoinflammatory and nutritional status to identify individuals at high risk of hip fracture and implement timely fracture interventions is particularly essential.

Clinical trial number: Not applicable.