In this retrospective study, we aimed to determine the incidence and distribution of fractures in patients with Alagille syndrome, one of the leading inherited causes of pediatric cholestatic liver disease.
Surveys regarding growth, nutrition, and organ involvement were distributed to patient families in the Alagille Syndrome Alliance or The Children’s Hospital of Philadelphia research database. Patients with a history of fracture were identified by their response to one question, and details characterizing each patient’s medical, growth, and fracture history were obtained through chart review and telephone contact.
Twelve of 42 patients (28%) reported a total of 27 fractures. Patients experienced fractures at a mean age of 5 years, which contrasts with healthy children, in whom fracture incidence peaks in adolescence. Fractures occurred primarily in the lower extremity long bones (70%) and with little or no trauma (84%). Estimated incidence rate calculations yielded 399.6 total fractures/10,000 person years (95% CI = 206.5, 698.0) and 127.6 femur fractures/10,000 person-years (95% CI = 42.4, 297.7). There were no differences in gender, age distribution or organ system involvement between the fracture and no-fracture groups.
Children with Alagille syndrome may be at risk for pathologic fractures, which manifest at an early age and in a unique distribution favoring the lower extremity long bones. While this preliminary study is limited by small sample size and potential ascertainment bias, the data suggest that larger studies are warranted to further characterize fracture risk and to explore factors contributing to bone fragility in these children.