Urinary pentosidine as a potential biomarker of impaired bone health: a systematic review and meta-analysis.

Background: Urinary pentosidine, an advanced glycation end product (AGE), has been proposed as a potential biomarker for impaired bone health, especially in older adults and those with diabetes. This study aimed to systematically review and meta-analyze the association of urinary pentosidine with bone mineral density (BMD) and fracture risk.

Methods: A comprehensive search of Embase, PubMed, Scopus, and Web of Science databases was conducted and records were gathered from 1960 to February 2024. Relevant papers were screened and data were extracted by two independent reviewers. Hedges' g standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated to compare urinary pentosidine levels between patients with and without fractures.

Results: A total of 12 studies comprising 5,878 participants were included in the systematic review. The meta-analysis revealed that patients with fractures had significantly higher urinary pentosidine levels compared to those without fractures (SMD [95% CI] = 0.53 [0.39-0.68]; I² = 54%;  < 0.01). In patients with vertebral fractures, pentosidine levels were also elevated (SMD [95% CI] = 0.51 [0.32-0.70]; I² = 64%;  < 0.01). Additionally, some studies demonstrated that an increase in urinary pentosidine was significantly associated with fracture risk (aHR = 1.20 [95% CI = 1.07-1.33];  = 0.001) and BMD reduction (β = -0.125 [95% CI = -0.248, -0.002];  = 0.047). However, other studies showed inconsistent results, particularly regarding the association between pentosidine and BMD or fracture risk in non-diabetic populations (aRR [95%CI] = 1.08 [0.79-1.49];  = 0.6). Diagnostic accuracy analyses revealed a sensitivity of 71.9% and specificity of 61.2% for urinary pentosidine in predicting vertebral fracture in patients with type 2 diabetes mellitus.

Conclusion: This systematic review and meta-analysis demonstrate that elevated urinary pentosidine levels are associated with an increased risk of fractures and, to a lesser extent, reduced bone mineral density. Its diagnostic accuracy improves when integrated with other clinical markers, such as BMD and bone turnover indices. However, due to the variability in results, further research is needed to standardize pentosidine's use as a reliable biomarker for impaired bone health in clinical practice.