Collagen overglycosylation: A biochemical feature that may contribute to bone quality

Skeletal ability to resist mechanical stress is determined by bone amount and quality, which relies on macro- and micro-architecture, turnover, bone matrix, and mineralisation; the role of collagen has not been clearly elucidated. Numerous post-translational steps are involved in collagen type I biosynthesis, including residue hydroxylation and glycosylation catalysed by enzymes that work until the protein folds forming the triple helix; therefore, folding rate regulates these processes. Overglycosylated hydroxylysines are poor substrates for ε-amino group deamination which initiates cross-link formation. Three clinical conditions associated with fractures may relate collagen overglycosylation with bone quality: (i) Osteogenesis Imperfecta, in which genetic mutations distort triple helix conformation and slow folding rate favouring overglycosylation; (ii) diabetes mellitus, with collagen overglycosylation by AGE accumulation; and, (iii) menopause, according to experimental studies demonstrating ovariectomy-related trabecular bone collagen overglycosylation preventable by 17β-estradiol or tamoxifen. Specific actions on collagen of drugs used for bone protection should be explored in future studies.