Serum albumin and the prognostic nutritional index independently predict fracture risk in elderly women

Serum albumin and the Prognostic Nutritional Index (PNI), based on albumin and lymphocytes, are markers of nutritional and inflammatory status and have been associated with frailty and adverse outcomes in older adults. However, their relationship with fracture risk and underlying mechanisms remains unclear. In this prospective cohort study, 2,966 community-dwelling Swedish women aged 75-80 years were followed for a median of 8.0 years. At baseline, blood samples were collected, bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry (DXA), and bone microarchitecture and composition were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Fractures were verified through regional X-ray archives, and injurious falls and mortality were obtained from registers. Physical function was assessed using standardized tests. Cox proportional hazards models and competing risk analyses were applied. PNI was defined as PNI = serum albumin (g/L) + 5 × total lymphocyte count (109/L). In total, 229 hip fractures, 789 major osteoporotic fractures (MOF), 1,059 fractures of any kind, 499 injurious falls, and 551 deaths occurred. Lower albumin and PNI were independently associated with increased risk of MOF (HR per 1 SD decrease: 1.13 [95% CI 1.06-1.22] and 1.18 [1.05-1.31], respectively; both p<0.01) and any fracture (HR: 1.12 [1.05-1.19] and 1.17 [1.07-1.29], respectively; both p<0.01), even after adjustment for clinical risk factors, femoral neck BMD and physical function. Albumin, and to a lesser extent PNI, was consistently associated with better physical function and lower risk of injurious falls and mortality. No significant associations were found between albumin or PNI and DXA-derived BMD, and only limited and inconsistent associations with HR-pQCT parameters. In conclusion, serum albumin and PNI independently predicted fracture risk in elderly women; however, the underlying mechanisms remain to be elucidated. Future studies should explore its contribution to fracture prediction models.