Background/Purpose: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility caused by mutations related to type 1 collagen biosynthesis. Fractures are a cardinal manifestation of OI, but fracture incidence across the lifespan is poorly understood. We used a large US-based cohort to describe fracture rates in individuals living with OI, stratified by clinical severity.

Methods: Individuals with OI were identified by ICD-9 (756.5) and/or ICD-10 (O78.0) diagnosis codes among ~30 million people included in MarketScan claims data (2006-2022) and a 5% random sample of US Medicare Fee-for-Service data (2006-2021). Severe OI was defined by long-term wheelchair use, identified using durable medical equipment (DME) claims. Incident fractures were identified using an adaptation of a previously validated algorithm with high specificity.

Results: We included 6,475 individuals with OI. Median age was 21.0 years (IQR: 8.0, 43.0) and severe OI was present in 20%. A reference cohort (N&#3f32,375) was matched 5:1 within each data source to those with OI by age, sex, race, index calendar year, and baseline length of continuous coverage. Median follow-up time was 2.1 years (IQR: 0.9, 4.5) in OI and 2.0 years (IQR: 0.8, 4.3) in the comparator group. In OI, the overall fracture rate was 129.6 (95% Cl: 124.7, 134.6) per 1000 person-years (py) vs 8.0 (95% CI: 7.4, 8.6) in the reference cohort (incidence rate ratio (IRR): 16.2, 95% Cl: 15.0, 17.2). Across all ages, the fracture rates were higher in severe vs milder OI (IRR: 238.6, 95% CI: 226.1, 251.7) vs 87.8 (95% CI: 83.2, 92.8) per 1000py (Figure 1). In both sexes, fracture rates were highest in childhood and lowest in early adulthood. In women with milder OI, fracture rates were highest at age 51 years and older, which coincides with the typical age range of menopause. In women with severe OI, the rates of fracture also increased in those aged 51 years and older. In men with milder OI fracture rates were stable with increased age, but were higher in older men with severe OI.

Conclusion: We report fracture rates stratified by sex, age and clinical severity in one of the largest datasets ever assembled of US individuals living with osteogenesis imperfecta. These data provide unique and necessary information for the clinical care of individuals living with OI and for the design of trials for new therapeutics.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/fracture-rates-in-6475-individuals-with-osteogenesis-imperfecta-stratified-by-age-sex-and-clinical-severity/