A higher serum gamma-glutamyl transferase level could be associated with an increased risk of incident osteoporotic fractures in Korean men aged 50 years or older

Abstract

With increasing life expectancies in men and greater comorbidity and mortality after hip fractures in men than in women [2], OFs in men will likely become a significant burden on society and healthcare systems in the future.Gamma-glutamyl transferase (GGT) has long been considered a sensitive marker of hepatic dysfunction or excessive alcohol intake [3]. However, accumulating evidence from epidemiological studies has shown that high levels of serum GGT, even within its reference range, can predict the incidence of cardiovascular disease (CVD), diabetes, and hypertension independently of alcohol consumption [4,5]. Although the exact mechanisms that link GGT with these diseases are not fully elucidated, GGT is known to play an A higher serum gamma-glutamyl transferase level could be associated with an increased risk of incident osteoporotic fractures in Korean men aged 50 years or older Abstract. Oxidative stress has detrimental effects on bone metabolism, and gamma-glutamyl transferase (GGT) is known to play an important role in the generation of free radical species through the extra-cellular hydrolysis of glutathione, the main cellular antioxidant. We performed a large longitudinal study with an average follow-up period of 3 years to investigate the association between baseline serum GGT levels and the development of future osteoporotic fractures (OFs) in men. A total of 16,036 Korean men aged 50 years or older who had undergone comprehensive routine health examinations were enrolled. Incident fractures at osteoporosis-related sites (e.g., hip, spine, distal radius, and proximal humerus) that occurred after baseline examinations were identified from the nationwide claims database of the Health Insurance Review and Assessment Service of Korea using selected ICD-10 codes. Among the study subjects, 156 cases (1.0%) developed incident OFs during the study period. The event rate was 32.7 (95% CI = 28.0-38.3) per 10,000 person-years. Multivariable adjusted Cox proportional hazard analyses adjusted for age, body mass index, lifestyle factors, and medical and drug histories revealed that the hazard ratio per standard deviation increase of the baseline GGT levels for the development of incident fractures was 1.115 (95% CI = 1.011-1.230). These data provide the first epidemiological evidence, in support of previous in vitro and animal studies, of the harmful effects of GGT on bone metabolism, and indicate that the serum GGT level may be a useful biomarker of poor bone health outcomes in men.

Association between liver enzymes and bone mineral density in Koreans: a cross-sectional study

“…GGT exhibited a relatively strong negative statistical significance with BMD at various sites in the current study, and the relationship between GGT and BMD has also been examined in numerous other studies [ 28 , 29 ]. A cross-sectional study conducted in 462 Korean adults demonstrated a negative relationship between serum GGT and BMD [ 30 ], and a large prospective cohort study on 16,036 Korean men aged ≥50 years found that elevated serum GGT levels at baseline were significantly associated with an increased incident of osteoporotic fractures over an average 3-year follow-up period, indicating that higher serum GGT levels may act as an independent risk factor for development of incidental fractures at osteoporosis-related sites in men [ 31 ]. In addition, Niida et al suggested that GGT stimulates the receptor activator of nuclear factor-kappa ß ligand expression and induces osteoclast formation [ 32 ], and GGT overexpression has been linked with accelerated bone resorption and osteoporosis development in transgenic mice [ 33 ], lending weight to the hypothesis that GGT may play a direct role in the pathogenesis of metabolic bone disease.…”

Gamma‐glutamyl transferase predicts future stroke: A Korean nationwide study

“…[1][2][3][4][5][6][7][8][9][10][11][12][13]18,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] International Classification of Disease-10th revision (ICD-10) codes for each disease and the generic name codes for drugs recorded in the NHIS-NSC were used to identify the aforementioned factors at the time of baseline examination. [1][2][3][4][5][6][7][8][9][10][11][12][13]18,[25][26][27][28][29][30][31][32]…”

“…Along with the abovementioned baseline data, the following factors were additionally sorted out from the database after literature review to assess potential factors that may influence GGT: various types of liver disease (hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, liver cirrhosis, primary or secondary liver cancer, etc), atrial fibrillation, ischemic heart disease, heart failure, cancer, chronic kidney disease, osteoporotic fracture, pregnancy, and antiepileptic drug (phenytoin, phenobarbital, carbamazepine, or valproate) or rifampicin use. [1][2][3][4][5][6][7][8][9][10][11][12][13]18,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] International Classification of Disease-10th revision (ICD-10) codes for each disease and the generic name codes for drugs recorded in the NHIS-NSC were used to identify the aforementioned factors at the time of baseline examination.…”

Associations Between Liver Function, Bone Turnover Biomarkers and Adipokines in Older Patients With Hip Fracture

“…In postmenopausal women urinary GGT excretion exhibited a high correlation with DPD [49]. A large longitudinal study (16,036 Korean men aged ≥ 50 years) demonstrated that a higher serum GGT level was associated with increased development of osteoporotic fractures over a mean 3-year follow-up period [50]. Experimental data indicate that both a deficiency and an excess of GGT result in osteoporosis [49,[51][52][53].…”