Urinary pentosidine improves risk classification using fracture risk assessment tools for postmenopausal women

Abstract

We investigated whether measurement of pentosidine, in addition to the conventional risk assessment tool, the Fracture and Immobilization Score (FRISC), improves early identification of fracture cases. A total of 765 postmenopausal Japanese women with baseline measurement of urinary pentosidine were followed in a hospital-based cohort study. Endpoints were incidence of vertebral fracture, incidence of long bone fracture, and incidence of long bone and vertebral fracture. To assess the effect of pentosidine on fracture risk, we fitted multivariate Cox regression models adjusted for age, body weight, diabetes mellitus, lumbar BMD, prior fracture, and presence of back pain. To explore potential nonlinear relationships, we fitted a multivariate generalized additive model. To assess the discriminatory power of pentosidine, we performed receiver operating characteristic analysis. The hazard ratios for a 1 SD increase in pentosidine were 1.18 (95% CI 1.05-1.33, p < 0.01) for vertebral fracture and 1.20 (95% CI 1.07-1.33, p < 0.01) for long bone and vertebral fractures. The relationship was approximately linear, and there was no indication of the presence of a threshold. The C statistics were 0.732 (95% CI 0.686-0.778) for the model with both pentosidine and the 10-year risk and 0.702 (95% CI 0.654-0.750) for the 10-year risk alone. Eighty-three subjects (11%) in the whole cohort were in the highest quartile of pentosidine, although their 10-year risks were less than 15% and included 17 incident vertebral fracture cases. Urinary pentosidine improves risk classification using conventional risk assessment tools. Optimal clinical strategies of diagnosis and treatment remain uncertain and in need of additional investigation. ß

The contribution of collagen crosslinks to bone strength

“…58 Similar findings were recently reported in a larger cohort of Japanese postmenopausal women ( Figure 5 ), with a moderate BMD-independent association of urinary pentosidine with incidence of vertebral and non-vertebral fractures. 59 Although there was also a significant association of urinary pentosidine with the risk of all fractures in 396 Figure 4 Relationship between AGE content in tibial cortical bone and post-yield work-to-fracture in dogs treated with two doses of alendronate (Aln, 0.2 and 1.0 mg kg − 1 ) and two doses of risedronate (0.1 and 0.5 mg kg − 1 ). Total AGE content was determined by fluorescence reading and using a quinine sulfate as a standard (from Tang et al 48 ).…”

The Effects of Diabetes and Obesity on the Skeleton

“…AGEs may decrease bone strength independent of BMD [ 43 ]. Urinary pentosidine predicted a higher risk of both vertebral and long bone fractures (HR 1.18, 95 % CI 1.05-1.33, p < 0.01) in postmenopausal diabetic women, suggesting that even in the absence of T2D, the accumulation of AGEs increases fracture risk, independent of BMD [ 44 ]. In T2D, pentosidine correlates with increased incidence of fracture [ 43 ].…”

Diagnosis and management of bone fragility in diabetes: an emerging challenge

“…Increased levels of serum pentosidine, AGEs, and soluble receptors for advanced glycation end products (sRAGE) were reported in type 2 diabetes compared with controls [75, 76]. Serum pentosidine was associated with greater risk of vertebral fracture in patients with type 2 diabetes [77], while urinary pentosidine is associated with an increased risk of clinical and vertebral fractures [78, 79]. Serum endogenous secretory RAGE (esRAGE) was inversely related to the risk of vertebral fracture in type 2 diabetes and the effect was independent of BMD [80].…”