Phenotypic Variability and Diagnostic Characteristics of Pediatric Osteogenesis Imperfecta: A 10-Year Multicenter Cohort Study from Three Tertiary Pediatric Hospitals in Bucharest, Romania

Background/Objectives: Osteogenesis imperfecta (OI) is a rare hereditary connective tissue disorder characterized by bone fragility, recurrent fractures, and variable extra-skeletal manifestations. There are scarce epidemiological and clinical data from Eastern Europe, including Romania. This study aimed to characterize the phenotypic spectrum and diagnostic features of pediatric OI in a Romanian multicenter cohort. Methods: A retrospective, multicenter observational study was conducted over a 10-year period (January 2014–December 2024) in three tertiary pediatric referral centers in Bucharest, Romania. Children with a diagnosis of OI based on clinical, radiological, and, where available, molecular criteria were included. Clinical, phenotypic, genetic, and therapeutic data were extracted from medical records. Statistical analyses included the Mann–Whitney U test, Kruskal–Wallis test with Bonferroni correction, Fisher’s exact test, Kaplan–Meier survival analysis, and Spearman correlation. Results: Forty-seven patients were included (53.2% female; median age at diagnosis 36 months, IQR 5–87). OI type I was the most frequent subtype (42.6%), followed by type III (29.8%) and type IV (21.3%). Molecular genetic testing was performed in 40.4% of patients; among genetically tested patients, COL1A1 variants represented the most common finding (52.6%). The median number of documented fractures was 5 (IQR 3–9), with a significantly higher annual fracture rate in type III compared to type I (0.99 vs. 0.34 fractures/year, p = 0.019). Short stature was the most frequent skeletal manifestation (66%), with significantly more severe growth impairment in type III compared to type I (−4.38 ± 1.67 vs. −1.56 ± 1.03 SD, p < 0.001). Blue sclerae was present in 87.2% of patients and dentinogenesis imperfecta in 68.1%. Cryptorchidism was identified in 50% of male patients. Developmental motor milestones were significantly delayed in type III OI patients, with 10.6% failing to achieve independent walking by last follow-up. A strong positive correlation was observed between age at first fracture and age at diagnosis (Spearman R = 0.764, p < 0.001), with type I patients diagnosed significantly later than type III (median 71.5 vs. 6.5 months, p = 0.006). Conclusions: This study provides the most comprehensive phenotypic characterization of pediatric OI reported from Romania to date. Our findings confirm established genotype–phenotype correlations and underscore the diagnostic challenge of milder OI forms. The high prevalence of cryptorchidism in male patients represents a clinically relevant finding needing prospective validation. The data highlight the need for expanded molecular diagnostic capacity, increased disease awareness among frontline clinicians, and the development of a national OI registry to support longitudinal research and integration with European rare bone disease networks.