Osteogenesis imperfecta – molekularna osnova i lijekovi budućnosti

Osteogenesis imperfecta (OI) or brittle bone disease is a metabolic bone disease characterized by bone fragility, low bone mass, and increased rate of bone fractures and deformities. Clinical presentation in OI patients shows wide variability ranging from mild to severe and lethal OI types. Advances in molecular biology and studies on animal OI models found at least 16 new genes involved in OI pathogenesis. The majority of mutations are autosomal dominant aff ecting COL1A1 and COL1A2 genes responsible for collagen synthesis. The remaining 10%-15% of mutations in OI are autosomal recessive and aff ect genes involved in various metabolic bone processes. Progress in understanding bone metabolism and genetic engineering off ers new potential therapeutic opportunities that are under diff erent stages of investigation.Osteogenesis imperfecta (OI) ili bolest krhkih kostiju je metabolička bolest kostiju obilježena krhkim kostima, niskom koštanom masom i povišenom stopom lomova i deformiteta kostiju. Klinička prezentacija bolesnika s OI veoma je raznolika, od blagog do teškog i smrtonosnog tipa OI. Napretkom molekularne biologije i istraživanjima na životinjskim modelima OI nađeno je najmanje 16 novih gena uključenih u patogenezu OI. Većina mutacija su autosomno dominantne i zahvaćaju gene COL1A1 i COL1A2 koji su odgovorni za sintezu kolagena. Preostalih 10%-15% mutacija u OI su autosomno recesivne i zahvaćaju gene uključene u razne metaboličke procese u kostima. Sve bolje razumijevanje metabolizma kostiju i genetski inženjering nude nove potencijalne terapijske mogućnosti koje su u različitim fazama ispitivanja