Elevated level of gamma-glutamyl transpeptidase is associated with an increased risk of hip fracture: a nationwide population-based study

초록

Serum gamma-glutamyl transferase (GGT) has long used as a marker of hepatic dys-function or excessive alcohol intake. However, accumulating evidence indicates that serum GGT level, as a marker of subclinical inflammation and oxidative stress, is also associated with cardiometabolic diseases, osteoporosis, or sarcopenia, independently of alcohol con-sumption or liver diseases. [1,2] Given the detrimental effect of oxidative stress on bone health, we hypothesized that GGT could be additionally a prognostic value for hip fracture. We analyzed individual nationwide health examination data retrieved from the Korean Na-tional Health Insurance Service claim database from 2003 to 2015. After excluding those with any chronic liver disease, history of heavy alcohol consumption, any missing values required for our analysis, or GGT level less than 1 percentile or more than 99 percentile, a total of 131,045 women aged 50 years or older were analyzed (GGT range: 7 to 107 IU/L). During 12.3 years of follow-up, 2,850 subjects sustained hip fracture (2.17%). Individuals with hip fracture had older age (67 vs. 60 years, p<0.001), higher prevalence of osteoporosis (12.4% vs. 6.4%), and higher GGT level (19.3 vs. 18.7, p=0.003) at baseline. One log-unit increase in GGT was associated with 17% elevated risk of hip fracture (adjusted hazard ratio 1.17, p<0.001) after adjustment for age, body mass index (BMI), alcohol consumption, comorbidities, liver enzyme levels (AST, ALT), and medication use including glucocorticoid and anticonvulsants. Subgroup analysis by BMI (>=25 vs. <25 kg/m2), presence of diabetes, and alcohol consumption level (mild to moderate vs. non-drinker) did not show significant effect modification (p for interaction>0.05 for all). Restricted cubic spline analysis based on Cox proportional hazard model showed linear increase of hip fracture risk according to GGT level (Figure 1) adjusted for age and BMI, particularly at GGT 50 IU/L or higher. In sum-mary, elevated GGT level was associated with increased risk of hip fracture in communi-ty-dwelling postmenopausal women independent of alcohol consumption and chronic liver diseases.