title: Collagen modifications in postmenopausal osteoporosis: advanced glycation endproducts may affect bone volume, structure and quality.
abstract: The classic model of postmenopausal osteoporosis (PM-OP) starts with the depletion of estrogen, which in turn stimulates imbalanced bone remodeling, resulting in loss of bone mass/volume. Clinically, this leads to fractures because of structural weakness. Recent work has begun to provide a more complete picture of the mechanisms of PM-OP involving oxidative stress and collagen modifications known as advanced glycation endproducts (AGEs). On one hand, AGEs may drive imbalanced bone remodeling through signaling mediated by the receptor for AGEs (RAGE), stimulating resorption and inhibiting formation. On the other hand, AGEs are associated with degraded bone material quality. Oxidative stress promotes the formation of AGEs, inhibits normal enzymatically derived crosslinking and can degrade collagen structure, thereby reducing fracture resistance. Notably, there are multiple positive feedback loops that can exacerbate the mechanisms of PM-OP associated with oxidative stress and AGEs. Anti-oxidant therapies may have the potential to inhibit the oxidative stress based mechanisms of this disease.
authors.affiliation: Musculoskeletal Research Laboratory, Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, 60 Murray Street, Box 42, Toronto, Ontario, Canada, M5T 3L9, willett@lunenfeld.ca.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Willett
authors.forename: Julia
authors.initials: J
authors.lastname: Pasquale
authors.forename: Marc D
authors.initials: MD
authors.lastname: Grynpas
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D009929:Organ Size; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000378:metabolism*; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; D017127:Glycation End Products, Advanced; D003094:Collagen