The Clinical Burden of Fractures in Osteogenesis Imperfecta: A Systematic Review
Author(s)
Samantha Prince, PhD1, Colin Song, BS2, Matthew Carter, MSc3, Ogün Sazova, MD1, James Clancy, BSc1, Clive Whitcher, PhD1.
1Mereo BioPharma Group plc, London, United Kingdom, 2Wickenstones, Great Neck, NY, USA, 3Wickenstones Ltd, Coventry, United Kingdom.
1Mereo BioPharma Group plc, London, United Kingdom, 2Wickenstones, Great Neck, NY, USA, 3Wickenstones Ltd, Coventry, United Kingdom.
OBJECTIVES: Osteogenesis imperfecta (OI) is associated with increased fracture susceptibility. Variability and manifestation of fractures in different OI populations are not yet fully understood. This systematic review aimed to consolidate literature on fracture burden in OI.
METHODS: 1) Comprehensive search of published literature to identify all potentially relevant records; 2) systematic selection of relevant records based on predefined inclusion criteria; and 3) data extraction from eligible records.
RESULTS: Records of 87 unique studies were included, 2 randomized controlled trials, 84 observational studies, and 1 survey. Most studies did not comprehensively document participant characteristics and treatment background nor conduct sub-group analyses based on age or OI type; there was limited geographic representation and marked heterogeneity of study design, size, and endpoint measurement. Average age at first fracture across OI types ranged from pre-birth to 11.5 years with most occurring before age 2 (n=24 studies). Fracture rates (n=70 studies) across cohorts varied widely with reported averages as high as 10.78 fractures per year; most reported fracture rates ranged up to 4 per year. Yearly rates reported by OI type (n=15 studies) indicated high upper ranges across all types (0.12-3.11 Type I; 0.57-10.78 Type III; 0.79-3.9 Type IV; 0.5-1.5 Type V, 1.4-3.1 Type VI and 2-2.8 Type XI). Children tended to fracture at a higher rate than adults (highest rates 4.94 and 2.44 fractures per year respectively; n=7 reports). Four studies reported fracture healing times ranging 4-8 weeks dependent on intervention and three studies described fracture-related events including pain, daily living and mobility limitations, and recurrent fractures.
CONCLUSIONS: Data suggest that fractures constitute substantial clinical burden for individuals of all OI types and rates can remain high as people with OI age. Further standardized data collection and analysis would allow a more nuanced understanding of driving factors across demographics.
METHODS: 1) Comprehensive search of published literature to identify all potentially relevant records; 2) systematic selection of relevant records based on predefined inclusion criteria; and 3) data extraction from eligible records.
RESULTS: Records of 87 unique studies were included, 2 randomized controlled trials, 84 observational studies, and 1 survey. Most studies did not comprehensively document participant characteristics and treatment background nor conduct sub-group analyses based on age or OI type; there was limited geographic representation and marked heterogeneity of study design, size, and endpoint measurement. Average age at first fracture across OI types ranged from pre-birth to 11.5 years with most occurring before age 2 (n=24 studies). Fracture rates (n=70 studies) across cohorts varied widely with reported averages as high as 10.78 fractures per year; most reported fracture rates ranged up to 4 per year. Yearly rates reported by OI type (n=15 studies) indicated high upper ranges across all types (0.12-3.11 Type I; 0.57-10.78 Type III; 0.79-3.9 Type IV; 0.5-1.5 Type V, 1.4-3.1 Type VI and 2-2.8 Type XI). Children tended to fracture at a higher rate than adults (highest rates 4.94 and 2.44 fractures per year respectively; n=7 reports). Four studies reported fracture healing times ranging 4-8 weeks dependent on intervention and three studies described fracture-related events including pain, daily living and mobility limitations, and recurrent fractures.
CONCLUSIONS: Data suggest that fractures constitute substantial clinical burden for individuals of all OI types and rates can remain high as people with OI age. Further standardized data collection and analysis would allow a more nuanced understanding of driving factors across demographics.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO237
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity), Rare & Orphan Diseases