OR03-3 High Spermidine Level was Associated with Increased Risk of Osteoporotic Fracture: A 10-Year Prospective Longitudinal Study in a Community-Based Cohort

Objective: As there have been no serum markers for fractures identified yet, we tried to identify metabolite parameters which can be a proxy for osteoporotic fracture risks. Method: In this community-based prospective cohort study, a total of 1,504 participants (842 women) were enrolled from Ansung, a rural county south of Seoul. We have measured baseline metabolite profiles which include 135 metabolites using targeted metabolomics in fasting serum. Cox regression analysis was performed to identify the significant metabolite, which can predict the osteoporotic fracture. The best cutoff value of serum spermidine level was calculated using SurvMisc R packages. Result: During a mean 9-year follow-up, 112 osteoporotic fracture events occurred. Of all metabolites measured, only serum spermidine levels were positively associated with the risk of fracture (hazard ratio [HR] per 1 μM of spermidine 1.41, 95% confidence interval [CI] 1.10-1.80, p=0.006) after adjustments for age, sex, body mass index, history of diabetes and hypertension, smoking status, serum creatinine, and previous fracture history. Participants who have more than 2.69 μM of serum spermidine concentrations had a 6.74-times higher risk of fractures (95% CI 2.45-18.56, p<0.001) compared with those with levels below or equal to 2.69 μM after adjustments for confounding variables described above. The increased risk of fracture at serum level above 2.69 μM was is found in both men and women (HR 6.61, 95% CI 1.59-27.48, p=0.009 in men; HR 6.69, 95% CI 1.56-28.62, p=0.010 in women). Among other metabolites, putrescine had a negative association with fractures only in women (HR 0.94, 95% CI 0.89-0.99, p=0.026). Conclusion: High spermidine levels were associated with an increased risk for osteoporotic fractures in a community cohort during a mean 9-year follow-up. The biological meaning and associations with other metabolite are subjects of future studies.