Osteoporosis and Aterosclerosis – is there Any Pathogenetic Association?

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Osteoporóza a ateroskleróza – je mezi nimi patogenetická souvislost?

Základním cytokinem regulujícím remodelaci kosti je ligand pro receptorový aktivátor nukleárního faktoru kappaB (RANKL). Protiregulačním faktorem je rozpustný receptor osteoprotegerin. Zatímco RANKL aktivuje osteoklastickou resorpci kosti, osteoprotegerin (OPG) stimuluje její novotvorbu. Systém RANKL/OPG (TRANCE osa) je aktivován ve prospěch RANKL při hypoestrinizmu, zánětu, léčbě glukokortikoidy a u kostních malignit. TRANCE osa je funkční i v dalších tkáních včetně cévní stěny, kde nerovnováha s převažující aktivitou RANKL urychluje aterogenezi. Molekuly blokující RANKL (specifické protilátky a OPG) jsou potencionálními léky osteoporózy, aterosklerózy, zánětlivých onemocnění, myelomu a osteolytických metastáz. Přehledný článek je zaměřen na úlohu TRANCE osy v patogenezi osteoporózy a aterosklerózy a její využití v diagnostice a léčbě obou degenerativních onemocnění.

Klíčová slova:
RANKL, osteoprotegerin, osteoporóza, ateroskleróza.

Authors: I. Žofková
Authors‘ workplace: Endokrinologický ústav, Praha
Published in: Čas. Lék. čes. 2007; 146: 246-250
Category: Review Article

Overview

Fundamental cytokine regulating remodelation of the skeleton is receptor activator of nuclear factor kappa B ligand (RANKL). RANKL is counter regulated by soluble receptor osteoprotegerin (OPG). While RANKL activates osteoclastic bone resorption, the OPG stimulates bone formation. RANKL/OPG system (TRANCE axis) is activated in favour of RANKL in estrogen deficiency, inflammation, bone malignancies and during the treatment with glucocorticoids. TRANCE axis is functional also in other tissues including vessel wall, where dysbalance with superiority of RANKL leads to atherogenesis. Molecules blocking RANKL (specific antibodies and OPG) are potential drugs for treatment of osteoporosis, atherosclerosis, inflammation diseases, myeloma or osteolytic bone metastases. This review is focused on pathogenetic role of TRANCE axis in the development of osteoporosis and atherosclerosis and on its use in diagnosis and treatment of both degenerative diseases.

Key words:
RANKL, osteoprotegerin, osteoporosis, atherosclerosis.

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