Dietary Advanced Glycation End Products Have Sex- and Age-Dependent Effects on Vertebral Bone Microstructure and Mechanical Function in Mice

Abstract

Back pain is a leading cause of global disability that can arise from vertebral fracture and osteoporosis. Although poor general health and obesity are among the strongest risk factors for back pain, there is remarkably little known about how diet influences spinal diseases. Advanced glycation end-products (AGEs) are implicated in increased fracture risk, yet no studies investigated how dietary AGEs affect spinal health. We tested the hypothesis that high dietary AGE ingestion will diminish vertebral structure and function in a sex- and age-dependent manner. Female and male mice were fed low-AGE (L-AGE) or high-AGE (H-AGE) isocaloric diets for 6 and 18 months and multiple measurements of bone structure and function were taken. AGE levels in serum and cortical vertebrae were increased only for 6-month-old H-AGE female mice while blood glucose and body weight remained normal for all animals. When fed an H-AGE diet, 6-month-old female mice had inferior vertebral trabecular structure with decreased bone mineral density (BMD) and bone volume fraction. Biomechanical testing and analytical modeling further showed functional deterioration in 6-month-old H-AGE females with reduced shear and compression moduli, and maximum load to failure. At 18 months, H-AGE mice of both sexes had significant but small decreases in cortical BMD and thickness, yet functional biomechanical behaviors were not distinguishable from other aging changes. We conclude that an H-AGE diet, without diabetic or overweight conditions, diminished vertebral microstructure, mechanical behaviors, and fracture resistance in young female mice in a manner suggesting accelerated bone aging. © 2017 American Society for Bone and Mineral Research.

Dietary Advanced Glycation End-Product Consumption Leads to Mechanical Stiffening of Murine Intervertebral Discs

“…Causes for the sex-dependent effects of dietary AGEs warrant future investigation, especially because estrogen is known to regulate cell metabolism (Mauvais-Jarvis et al, 2013) and to influence the receptor for AGEs (Tanaka et al, 2000). We previously have shown that dietary AGEs affect bone mechanical properties mostly in young female mice (Illien-Junger et al, 2018), which further emphasizes the importance of assessing male and females separately.…”

“…Recently, we showed in ageing pre-diabetic mice, that chronic ingestion of diets enriched with the specific AGE precursor (methylglyoxal) accelerated agerelated vertebral bone loss and induced AGE accumulation within the endplate (Illien-Junger et al, 2015). When further investigated, ingestion of dietary AGEs induced sex dependent bone loss with inferior biomechanical properties in young (6m) female mice (Illien-Junger et al, 2018). These studies provided the first evidence that dietary AGEs had a direct effect on vertebral structure and function, and also showed that this effect was sex-dependent.…”

Skin Autofluorescence, a Noninvasive Biomarker for Advanced Glycation End-Products, Is Associated With Prevalent Vertebral and Major Osteoporotic Fractures: The Rotterdam Study

“…A study in young female mice fed with a high-AGE diet for 6 months showed deterioration of vertebral microarchitecture and a decrease in fracture resistance. (47) in vitro glycation studies, on biopsy specimens from both living donors and cadavers, showed that cancellous bone is more susceptible to non-enzymatic glycation than cortical bone. (48,49) The more efficient glycation of bone matrix proteins in cancellous bone is due to higher surface area to volume ratio, which could have facilitated better accessibility of the sugars to the matrix proteins.…”

Prior-Knowledge-Driven Local Causal Structure Learning and Its Application on Causal Discovery Between Type 2 Diabetes and Bone Mineral Density

“…After bone mass reaches a peak in the third or fourth decade of life, vertebral bone mass and density decrease with aging for both females and males [43]. Moreover, AGEs accumulation occurs in the bone with aging, increasing by 4 to10 fold at the age, of 50 years old [44]. [45], [46].…”