Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease

Abstract

Aim: Osteoporotic fractures negatively impact health-related quality of life and prognosis. Advanced glycation end products (AGEs) impair bone quality and reduce bone strength. The aim of this study was to determine the relationship between plasma levels of pentosidine, a surrogate marker for AGEs, and prevalent fractures in patients with chronic liver disease (CLD).

Methods: This cross-sectional study included 324 patients with CLD. Vertebral fractures were evaluated using lateral thoracolumbar spine radiographs. Information on prevalent fractures was obtained through a medical interview, medical records, and/or radiography. The patients were classified into low (L), intermediate (I), and high (H) pentosidine (Pen) groups based on baseline plasma pentosidine levels.

Results: Of the 324 patients, 105 (32.4%) had prevalent fractures. The prevalence of liver cirrhosis (LC) and prevalent fractures significantly increased stepwise with elevated pentosidine levels. The H-Pen group had the highest prevalence of LC (88.6%, p < 0.001) and prevalent fractures (44.3%, p = 0.007), whereas the L-Pen group had the lowest prevalence of LC (32.1%, p < 0.001) and prevalent fractures (21.0%, p = 0.007). Multiple logistic regression analysis identified pentosidine as a significant independent factor related to prevalent fractures (odds ratio = 1.069, p < 0.001). Pentosidine levels increased stepwise and correlated with liver disease severity. They were markedly high in patients with decompensated LC. In multiple regression analysis, liver functional reserve factors (total bilirubin, albumin, and prothrombin time-international normalized ratio) significantly and independently correlated with pentosidine levels.

Conclusions: Plasma pentosidine was significantly associated with prevalent fractures and liver functional reserve in patients with CLD. Pentosidine may be useful in predicting fracture risk and should be closely followed in CLD patients with advanced disease.

Fig 1. Comparison of clinical characteristics among the low (L)-pentosidine (Pen), intermediate (I)-Pen, and high (H)-Pen groups.

The (A) total bilirubin levels and (B) prothrombin time-international normalized ratio were significantly higher in the H-Pen group than in the L-Pen and I-Pen groups. (C) The levels of albumin were significantly lower in the H-Pen group than in the L-Pen and I-Pen groups. The (D) creatinine levels were significantly higher and (E) estimated glomerular filtration rate was significantly lower in the I-Pen and H-Pen groups than in the L-Pen group. (F) The levels of mac-2 binding protein glycosylation isomer were highest among the H-Pen group. (G) (H) (I) The H-Pen group had the highest prevalence of liver cirrhosis (chi-squared test: p < 0.001), chronic kidney disease (chi-squared test: p = 0.008), and prevalent fractures (chi-squared test: p = 0.007) among the three groups. C-A, Cochran–Armitage trend test; C-S, chi-squared test.

Fig 2. Relationship between plasma pentosidine levels and Child-Pugh class.

(A) The plasma pentosidine levels were significantly higher in patients with Child-Pugh class B and C [decompensated liver cirrhosis (LC)] than in those with non-LC and Child-Pugh class A (compensated LC), and (B) significantly correlated with Child-Pugh scores in patients with LC.

Fig 3. Comparison of the prevalence of prevalent fractures among four groups.

(1) the osteoporosis (−)/high pentosidine levels (−) group, (2) the osteoporosis (−) / high pentosidine (+) group, (3) the osteoporosis (+)/high pentosidine (−) group, and (4) the osteoporosis (+) /high pentosidine (+) group. The prevalence of prevalent fractures was significantly highest in the osteoporosis (+) /high pentosidine (+) group (chi-squared test: p < 0.001). The prevalence of prevalent fractures significantly increased stepwise with complications of high pentosidine levels and/or osteoporosis (Cochran–Armitage trend test: p < 0.001). C-A, Cochran–Armitage trend test; C-S, chi-squared test.