Fracture characteristics and outcomes in osteogenesis imperfecta: A systematic review

Abstract

Objectives Osteogenesis imperfecta (OI) is a rare genetic disorder marked by bone fragility and increased fracture risk, adversely affecting quality of life (QoL). The overall fracture burden remains incompletely defined. This systematic review synthesised evidence on fracture characteristics (onset, frequency, anatomical location, risk factors) and outcomes (healing time and downstream signs, symptoms, and events [SSEs]). Methods We sought English-language cohort studies, patient surveys, and trials enrolling ≥10 individuals with OI, reporting fracture characteristics and fracture outcomes, published in or after 2000. We searched MEDLINE, Embase, Cochrane CENTRAL, PsycINFO, ClinicalTrials.gov, ICTRP, and CPCIS-S through March 15, 2024 and relevant congresses through December 31, 2024. Outcomes were qualitatively synthesised. Results Most included studies (n = 87) were retrospective. First fractures typically occurred in early childhood, with earlier onset in those with Type III versus Type I. Annual fracture rates ranged from 0 to >10, varying by OI type; one to several fractures per year were typical. Fractures affected long bones, vertebrae, and other bones without a predominant location, likely reflecting heterogeneous reporting. Fracture rates were slightly higher in children than adults, and highest in those with Type III across ages. Few healing-time data were available. Downstream SSEs included pain, impaired functioning and QoL, and risk of same-site refracture. Discussion OI is associated with an early-onset, lifelong fracture burden, with considerable individual variability. Interpretation is limited by heterogeneous study designs, inconsistent fracture recording, and limited prospective data. Findings highlight a heavy fracture burden and a considerable unmet need for effective interventions to prevent OI-related fractures. Registration: PROSPERO (CRD42024536760).