Growth differentiation factor 15 and the risk of hip fracture in older adults

Growth differentiation factor 15 (GDF15) is a protein that is produced by senescent cells during the aging process. Its level in blood increases with age and is associated with an increased risk of several age-related diseases and mortality. We measured GDF15 level in serum archived 1174 men and women aged between 70 and 79 yr in the Health Aging and Body Composition study who had measurements of BMD of the hip, markers of bone turnover (PINP and CTX) and tested for several physical functions (6 m gait speed, standing balance and grip strength, BMI, and appendicular lean mass) and falls, and were followed-up for incident fracture. Cox proportional hazard models were used to estimate hip fracture risk by increasing GDF15 quartiles. The mean GDF15 was significantly higher in men than in women (p < .0001) and the level significantly increased with age, slower gait speed, lower standing balance test time, and lower handgrip strength. During 11.5 (SD 4.5) yr of follow-up, 93 (8%) of the participants suffered a hip fracture and the risk was higher among women (p < .015), associated with older age, lower BMI, lower FN and TH BMD, lower appendicular lean mass, and weaker grip strength. In the unadjusted hazard model participants in the highest quartile of GDF15 had a 2-fold increased hip fracture risk (HR 2.12, p < .014) that remained significant after adjustment for age and sex (p < .037). However, the association was no longer statistically significant after adjusting for grip strength (HR 1.8, 95% CI: 0.97-3.34; p < .06). In conclusion, increased GDF15 is a predictor of hip fractures. This relationship might be partially mediated by muscle function and low lean mass but not BMD.