Elevated gamma-glutamyl transpeptidase level is associated with an increased risk of hip fracture in postmenopausal women

Kim, Kyoung Jin; Hong, Namki; Yu, Min; Lee, Seung–Hyun; Shin, Sungjae; Kim, Sin Gon; Rhee, Yumie

doi:10.1038/s41598-022-18453-9

Cited by 6 publications

(4 citation statements)

References 29 publications

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“…GGT also exhibits sexspecific differences that showed a similar dynamic as AP in females. In line with these findings increased GGT levels have been suggested as an early marker for oxidative stress associated with pathological diseases beyond liver damage, including abnormal bone metabolism and a higher risk of hip fractures in women [35]. These elevations are not as pronounced as in liver diseases and therefore may still be within the reference interval but nevertheless can lead to a shift of the upper TML-RL.…”

Section: Flagmentioning

confidence: 66%

Comparison of age- and sex-dependent reference limits derived from distinct sources for metabolic measurands in basic liver diagnostics

et al. 2023

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Background Reference intervals for basic liver laboratory diagnostic rely on manufacturers’ information, remaining unchanged for more than 20 years. This ignores known age and sex dependencies. Methods We performed a retrospective cross-sectional study to compare the age-dependent distribution of flagged and non-flagged laboratory findings between reference limits from 3 distinct sources: manufacturer, published reference study, and the truncated maximum likelihood method applied on a cohort of inpatients aged 18–100 years. Discordance rates adjusted for the permissible analytical uncertainty are reported for serum levels of albumin (n= 150,550), alkaline phosphatase (n= 433,721), gamma-GT (n=580,012), AST (n= 510,620), and ALT (n= 704,546). Results The number of flagged findings differed notably between reference intervals compared, except for alkaline phosphatase. AST and alkaline phosphatase increased with age in women. Overall discordance for AP, AST, and ALT remained below 10%, respectively, in both sexes. Albumin decreased with age which led to discordant flags in up to 22% in patients ≥70 years. GGT and ALT peaked in 50–59-year-old men with up to 23.5% and 22.8% discordant flags, respectively. Conclusion We assessed the impact of different reference limits on liver related laboratory results and found up to 25 % discordant flags. We suggest to further analyse the diagnostic and economic effects of reference limits adapted to the population of interest even for well-established basic liver diagnostics.

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Section: Flagmentioning

confidence: 66%

Comparison of age- and sex-dependent reference limits derived from distinct sources for metabolic measurands in basic liver diagnostics

et al. 2023

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“…(31) Large population-based cohort studies have also recently confirmed a significant association between GGT level and hip fracture risk. (32,33) However, there has been no previous study using GGT variability as a biomarker for risk assessment of osteoporotic fractures. The high variability of biomarkers has been attracting attention as a new factor predicting poor clinical outcomes of various diseases, and high GGT variability was identified as a predictor of increased risk of myocardial infarction, stroke, dementia, chronic kidney disease, and mortality.…”

Section: Discussionmentioning

confidence: 99%

Association of gamma-glutamyl transferase variability with risk of osteoporotic fractures: A nationwide cohort study

Song

Kim

et al. 2022

Preprint

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Objectives: Gamma-glutamyl transferase (GGT) is related to inflammation, osteoporosis, and vascular diseases. Recently, changes in metabolic parameters have been proposed as disease biomarkers. We aimed to assess longitudinally the association of GGT variability with osteoporotic fractures. Methods: From the National Health Insurance Service-Health Screening Cohort database, participants who underwent three or more health examinations between 2003 and 2008 were included (n=1,072,432). Variability indexes were as follows: (1) coefficient of variation (CV), (2) standard deviation (SD), and (3) variability independent of the mean (VIM). The primary outcome was occurrence of osteoporotic fracture, defined as identification of one of the following international classification of diseases-10 codes: vertebral fracture (S22.0, S22.1, S32.0, S32.7, T08, M48.4, M48.5, M49.5), hip fracture (S72.0, S72.1), distal radius fracture (S52.5, S52.6), or humerus fracture (S42.2, S42.3). Results: During a median of 12.3 years (interquartile range 12.1 – 12.6), osteoporotic fractures occurred in 49,677 (4.6%) participants. In multivariable analysis, GGT variability based on CV positively correlated with the occurrence of osteoporotic fracture (adjusted hazard ratio [HR]of the highest quartile compared with the lowest quartile 1.15, 95% confidence interval [CI] 1.12-1.18, P < 0.001). These results were consistent even when GGT variability was defined by SD (adjusted HR 1.22, 95% CI 1.19-1.25, P < 0.001) and VIM (adjusted HR 1.12, 95% CI 1.09-1.15, P < 0.001). Conclusions: Increased GGT variability is associated with an increased risk of osteoporotic fractures in the Korean population. Maintaining constant and stable GGT level may help reduce the risk of osteoporotic fractures.

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“…Large population-based cohort studies have also recently confirmed a significant association between GGT level and hip fracture risk [10,36]. However, there has been no previous study using GGT variability as a biomarker for risk assessment of osteoporotic fractures.…”

Section: Plos Onementioning

confidence: 96%

Association of gamma-glutamyl transferase variability with risk of osteoporotic fractures: A nationwide cohort study

Kim

Lee

et al. 2023

PLoS ONE

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Objectives Gamma-glutamyl transferase (GGT) is related to inflammation, osteoporosis, and vascular diseases. Recently, changes in metabolic parameters have been proposed as osteoporosis biomarkers. We aimed to assess longitudinally the association of GGT variability with osteoporotic fractures. Methods From the National Health Insurance Service-Health Screening Cohort database, participants who underwent three or more health examinations between 2003 and 2008 were included (n = 1,072,432). Variability indexes were as follows: (1) coefficient of variation (CV), (2) standard deviation (SD), and (3) variability independent of the mean (VIM). The primary outcome was occurrence of osteoporotic fracture, defined as identification of one of the following international classification of diseases-10 codes: vertebral fractures (S22.0, S22.1, S32.0, S32.7, T08, M48.4, M48.5, M49.5), hip fractures (S72.0, S72.1), distal radius fractures (S52.5, S52.6), or humerus fractures (S42.2, S42.3). Results During a median of 12.3 years (interquartile range 12.1–12.6), osteoporotic fractures occurred in 49,677 (4.6%) participants. In multivariable analysis, GGT variability based on CV positively correlated with the occurrence of osteoporotic fracture (adjusted hazard ratio [HR] of the highest quartile compared with the lowest quartile 1.15, 95% confidence interval [CI] 1.12–1.18, P < 0.001). These results were consistent even when GGT variability was defined by SD (adjusted HR 1.22, 95% CI 1.19–1.25, P < 0.001) and VIM (adjusted HR 1.12, 95% CI 1.09–1.15, P < 0.001). Conclusions Increased GGT variability is associated with an increased risk of osteoporotic fractures in the Korean population. Maintaining constant and stable GGT level may help reduce the risk of osteoporotic fractures.

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Elevated gamma-glutamyl transpeptidase level is associated with an increased risk of hip fracture in postmenopausal women

Cited by 6 publications

References 29 publications

Comparison of age- and sex-dependent reference limits derived from distinct sources for metabolic measurands in basic liver diagnostics

Comparison of age- and sex-dependent reference limits derived from distinct sources for metabolic measurands in basic liver diagnostics

Association of gamma-glutamyl transferase variability with risk of osteoporotic fractures: A nationwide cohort study

Association of gamma-glutamyl transferase variability with risk of osteoporotic fractures: A nationwide cohort study

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