Osteogenesis imperfecta (OI), also known as brittle bone disease, is a genetic, heritable bone fragility disorder caused by the impairment of the bone collagen network and characterized by skeletal deformities and frequent fractures (Chabot and Zeitlin, 2004, Fritz et al., 2009a). This rare disease has a reported prevalence of 1 in 10,000 (Marini et al., 2017), afflicting approximately 25,000–50,000 people in the United States (The Osteogenesis Imperfecta Foundation Inc., 2025). OI types can range from mild to severe, characterized by varying severity of bone deformity and fracture incidence, amongst other traits (Albert et al., 2017, Chabot and Zeitlin, 2004, Chiasson et al., 2004, Marlowe et al., 2002, Shapiro et al., 2014, Sillence et al., 1979, Sun et al., 2024, Zimmerman et al., 2024). Type I OI is the mildest and most commonly occurring type, described by few skeletal deformities, limited fractures, and nearly normal stature. Type III is the most severe type of OI compatible with life, and clinically presents with severe progressive deformities, frequent fractures, and severe short stature. OI types IV, VI, VII, and VIII, all which fall between OI types I and III in severity, are characterized by frequent fractures, bony deformities, and short stature. These types are further classified based on their phenotype, timing of fracture onset, progression of skeletal deformities, and by unique characteristics, such as the presence of osteomalacia in OI type VI, rhizomelic shortening of the femora and humeri in OI type VII, and gracile ribs without beading in OI type VIII (Chiasson et al., 2004, Shapiro et al., 2014, Zimmerman et al., 2024). In all cases of moderate to severe OI in children, progressive bowing of the long bones is frequently observed, which could be attributed to recurrent fractures and growth (Fassier, 2004).

Finite element modeling of cortical OI bone may be utilized to better quantify fracture risk and design of rehabilitative interventions for improved orthopaedic treatment (Fritz, 2016). However, lack of appropriate material properties for these computational models remains a major challenge (Varga et al., 2020) with only limited studies characterizing the macroscopic cortical bone mechanical properties in children with OI. Prior studies have presented weakened mechanical properties in children with OI compared to pediatric controls and anisotropy with reduced elastic modulus and strength in the transverse orientation compared to the longitudinal orientation (Albert et al., 2017, Albert et al., 2014, Imbert et al., 2015). Furthermore, previous studies have demonstrated less pronounced anisotropy in OI bone compared to normal pediatric bone (Albert et al., 2017). However, these studies examined mechanical properties in groups with small sample sizes for OI types limited to I, III, IV, and VIII.

The objective of this study was to compare the cortical bone macroscopic mechanical properties and anisotropy in three-point bending between phenotypes in pediatric OI and control bones. This study encompassed larger sample sizes of type I, III, IV, and VIII OI bone samples to perform robust statistical analyses and performed the first mechanical characterization of OI type VI and VII bone. Quantification of mechanical properties of pediatric cortical OI bone based on orientation may be used for more biofidelic finite element models to predict fracture during ambulation and daily activities in pediatric OI patients (Albert et al., 2014, Albert et al., 2017; C. I. Albert et al., 2013; Imbert et al., 2015, Vardakastani et al., 2014).