Studi Molecolari in Pazienti clinicamente selezionati affetti da forme particolari di Osteogenesi Imperfetta

Osteogenesis Imperfecta (OI) is a rare connective tissue defect characterised by high bone fragility. In the last years it has become more heterogeneous than it was believed to be, since its molecular basis are being discovered. The treatment of this condition is based on the use of anti-resorbitive drugs such as bisphosphonates (BPs), but it has clearly emerged that the use of BPs could be in a way harmful or at least ineffective in some OI types. The recent recognition of multiple molecular basis in the genesis of OI, involving not only genes related to collagen assembly and processing, but also the regulation of osteoblast development has illuminated the details of the collagen processing pathway. New therapies that would be specific for single-gene disorders and identify cellular targets in individuals with OI are ongoing trials. The aim of this research is take advantage of the multimodal imaging, in its wider meaning, to clarify the characteristics of the new OI subtypes in order to offer the best possible evaluation for each patient on the basis of their complex condition. In particular the multimodal imaging is intended as the physical examination and the dysmorphologic examination, integrated to classical radiologic imaging (X-rays, DXA, morphometry) and biological data (both routine and experimental assays through ELISA), leading to the development of groups of selected patients that are further studied with histological samples (using both optic, electronic and confocal microscopy) and protein mono and bidimensional electrophoresis to obtain a molecular diagnosis (DHPLC, DNA microarray e DNA sequencing) and therefore to outline a more targeted treatment. In this thesis the clinical history, the clinical phenotypes, the biological, radiological and molecular aspect of 23 patients affected by non classical forms of OI have been considered: OI V (1), OI VI (10), OI VII (1), OI VIII (2), OI XI (1). These results offer the basis for further studies aiming to calculate the incidence of non classical OI subtypes and identifying the best treatment for each subtype of OI, on the basis of the genetic defects and therefore of the patogenesis of the disease.