Association of plasma levels of protein-bound advanced glycation end-products and their soluble receptors with bone mineral status in young girls with the restrictive type of anorexia nervosa

Abstract

Summary

In diabetes- and age-related osteopenia/osteoporosis, a pathogenetic role of advanced glycation end-products and their soluble receptors (RAGE) is implicated. We studied how these compounds relate to bone health in girls with anorexia nervosa. We found that higher levels of endogenous secretory RAGE were associated with poorer bone quality, warranting further research.

Purpose

We explored the association of plasma protein–bound advanced glycation end-products (AGEs) and their soluble receptors with bone mineralization and turnover markers in girls with a restrictive type of anorexia nervosa.

Methods

A total of 102 girls with anorexia nervosa aged 14.0 ± 2.7 years and 29 age-matched healthy controls were included. Plasma levels of chemically defined AGEs (N^ε-(carboxymethyl)-lysine, methylglyoxal-derived hydroimidazolone-1, and their soluble receptors were determined using the ELISA methods; parathormone, osteocalcin, amino-terminal propeptide of human procollagen type I, carboxy-terminal telopeptide of type I collagen (CTX), and estradiol using the electrochemiluminescence. Girls with AN underwent dual-energy X-ray absorptiometry to assess bone mineral density (BMD) and trabecular bone score (TBS). Multivariate regression was performed using the orthogonal projection to latent structures model.

Results

Girls with anorexia nervosa displayed higher plasma levels of N^ε-(carboxymethyl)-lysine (by 52%) and methylglyoxal-derived hydroimidazolone-1 (by 34%) than controls, while soluble RAGE levels were similar in both groups. In girls with anorexia nervosa, low levels of nutritional markers, high endogenous secretory RAGE, and high CTX predicted low hip and femoral neck BMD. Low levels of nutritional markers and high bone turnover markers predicted TBS.

Conclusions

To clarify the role of the AGEs/RAGE axis in anorexia nervosa-associated low bone mass, longitudinal studies assessing the dynamic changes of these markers during re-alimentation-induced weight restoration and bone health recovery are needed. In clinical practice, monitoring of the AGEs/sRAGE axis could offer a novel approach for assessing disease status and guiding personalized interventions to mitigate long-term health consequences in patients with AN.