Craniofacial and whole-skeleton fracture patterns in osteogenesis imperfecta: Findings from a nationwide U.S. insurance claims database.

Abstract

Osteogenesis imperfecta (OI) is an inherited connective tissue disease characterized by lifelong skeletal fragility and recurrent fractures. While most prior research has focused on long bone fractures in selected clinical cohorts, population-based estimates of craniofacial and site-specific fracture risk in OI remain largely limited. This study used insurance claims data to quantify the period prevalence, anatomical distribution, and predictors of fractures in individuals with versus without OI. A retrospective cohort study was conducted using the IBM® MarketScan® Multi-State Medicaid (2016-2022, all ages) and Commercial Databases (2016-2022, < 65 years old). Diagnosis of OI and all fractures were identified using ICD and CPT codes recorded during healthcare encounters. The first full year of enrollment was used to determine 1-year period prevalence and counts of fractures overall and by site, stratified by age (<5, 6-9, 10-13, 14-18, 19-25, ten-year intervals to >55). Differences between cohorts were estimated using relative risk (RR). Associations with demographic and clinical factors were assessed via logistic regression. Proxy measures of OI severity and medical device use were applied, as clinical classification and exposure to treatments could not be directly adjudicated. Among 4294 individuals with OI and approximately 54.8 million controls, the overall fracture prevalence was 33.9 % in the OI cohort versus 2.5 % in controls (RR 13.6), with elevated rates observed at all anatomical sites. Jaw (craniofacial) fractures were nearly seven times more frequent in OI (0.40 % vs. 0.06 %; RR 6.7), while femur fractures showed the greatest disparity (RR 119.4). Age-specific analysis revealed the highest fracture risk for individuals with OI in early childhood, particularly at craniofacial and axial sites, with risk increasing further in those with greater proxy-measured disease severity. Female was associated with lower odds of fracture compared to males, and Medicaid coverage correlated with increased risk at select skeletal sites. Limitations include inability to distinguish fracture etiology (spontaneous, traumatic, or iatrogenic), unmeasured exposure to treatments, inability to apply clinical OI classifications, and exclusion of uninsured individuals. Individuals with OI face a markedly greater and distinctive burden of fractures, including craniofacial involvement, than the general population. This work provides the first large-scale, population-based estimates of craniofacial fracture burden in OI, highlighting distinct age- and site-specific risk patterns. These findings reinforce the importance of ongoing, site-specific monitoring and integrated multidisciplinary care for individuals with OI, supporting clinicians in anticipatory guidance and tailored prevention strategies.