Correlation of the first fracture time and COL1A1/2 mutations in patients with Osteogenesis Imperfecta

Abstract

Osteogenesis Imperfecta (OI) is a brittle bone disease, characterized with reduced bone mass and bone fragility of different severity due to collagen type I defects. Patients suffer from recurrent spontaneous fractures starting in the early childhood or before birth. The main aim of the study was to relate time of the first fracture with COL1A1/2 mutations causing OI. Total number of 167 unrelated OI patients from the Osteogenesis Imperfecta database of Tartu University Department of Traumatology and Orthopeadics, were included in the study. Data of OI genotypes was recruited from previous Sanger sequencing mutational analysis of the COL1A1/2 genes. Time of the first fracture was recorded from patients’ words and divided into categories: intrauterine, perinatal, 0–6 and ≥7 years old. Significance of correlations between time of the first fracture and COL1A1/2 mutations was tested with Fisher’s test. Among 167 analysed patients, 29 (17.37%) had intrauterine fractures, 21 (12.57%) had perinatal fractures, 106 (63.47%) had fractures at the age 0–6 years old, 8 patients (4.79%) at ≥7 years old, and 3 (1.80%) patients had no fractures. Number of patients harbouring collagen I mutations was 103 (61.68%). The statistically significant correlation between the first fracture time and COL1A1/2 mutations was highlighted during the study (P=0.0288). Exploring of the relation between type of the COL1A1/2 mutations and time of the first fracture, showed connection between quality collagen mutations and earlier time of the first fracture (P=0.0414). Intrauterine fractures did not reveal correlation with presence of the COL1A1/2 mutations (P=0.8339), however showed correlation with collagen I quality mutations (P=0.0270). Perinatal fractures, represented mostly with fractures happened during delivery, did not reveal correlations with presence (P=0.8180) or type (P=1) of the COL1A1/2 mutations. Our results show general correlation between time of the first fracture and presence of the COL1A1/2 mutations. Quality collagen mutations are related to the earlier time of the first fracture. Despite the clear genetic background of bone fragility phenotype in OI patients, minor variations in time of the first fracture in OI patients might come from additional non-genetic factors.