AGEs Contribute to the Development of Osteoporosis

Osteoporosis is the characteristic loss of bone mass and strength that occurs with aging, with proximate causes that include an imbalance in the distinct populations of cells responsible for bone creation and destruction, as well as the general decline in stem cell maintenance activities that occurs for every tissue in the body. For root causes you have to look to cellular and molecular damage of the sort listed in the SENS research programs, which include an accumulation of sugar-based metabolic waste molecules called advanced glycation endproducts (AGEs). These gum together important proteins in the extracellular matrix between cells and degrade tissue elasticity, but they also trigger increased levels of chronic inflammation through reacting with RAGE, the receptor for AGEs. Chronic inflammation is an unpleasant thing, a source of damage and dysfunction in and of itself, and it contributes meaningfully to many age-related conditions - such as osteoporosis.

Among the wide spectrum of bone disorders, osteoporosis has emerged as a medical and socioeconomic threat. Although it is accepted that more than 8.9 million fractures annually worldwide are caused by osteoporosis, they are often diagnosed only after the first clinical fracture has occurred because bone loss arises insidiously and is initially asymptomatic. The lifetime fracture risk of a patient with osteoporosis has been estimated to be in the order of 30-40%, which is very close to the risk for coronary heart disease. Moreover, in addition to pathologic fractures, osteoporosis carries a considerable risk of disability due to serious medical complications. With the aging of the population, the prevalence of osteoporosis is expected to further increase.

In the last twenty years, advanced glycation end products (AGEs) have been shown to be critical mediators both in the pathogenesis and development of osteoporosis and other chronic degenerative diseases related to aging. The accumulation of AGEs within the bone induces the formation of covalent cross-links with collagen and other bone proteins which affects the mechanical properties of tissue and disturbs bone remodelling and deterioration, underlying osteoporosis. On the other hand, the gradual deterioration of the immune system during aging (defined as immunosenescence) is also characterized by the generation of a high level of oxidants and AGEs. The synthesis and accumulation of AGEs (both localized within the bone or in the systemic circulation) might trigger a vicious circle (in which inflammation and aging merged in the word "Inflammaging") which can establish and sustain the development of osteoporosis.



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