Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease

Context: Pediatric Crohn's Disease (CD) is associated with deficits in trabecular bone mineral density (BMD) and cortical structure, potentially related to TNF-alpha effects to decrease bone formation and promote bone resorption. Objective: This study aimed to examine changes in bone density and structure in children and adolescents with CD following initiation of anti-TNF-alpha therapy. Design and Participants: Participants (n = 74; age 5-21 years) with CD completed a 12-month prospective cohort study. Main Outcome Measures: Tibia peripheral quantitative computed tomography scans were obtained at initiation of anti-TNF-alpha therapy and 12 months later. Musculoskeletal outcomes were expressed as sex-and race-specific z scores relative to age, based on >650 reference participants. Results: At baseline, CD participants had lower height, trabecular BMD, cortical area (due to smaller periosteal and larger endocortical circumferences), and muscle area z scores, compared with reference participants (all P <.01). Pediatric CD activity index decreased during the 10-week induction (P <.001), in association with subsequent gains in height, trabecular BMD, cortical area (due to recovery of endocortical bone), and muscle area z scores over 12 months (height P <.05; others P <.001). Bone-specific alkaline phosphatase levels, a biomarker of bone formation, increased a median of 75% (P <.001) during induction with associated 12-month improvements in trabecular BMD and cortical area z scores (both P <.001). Younger age was associated with greater increases in trabecular BMD z scores (P <.001) and greater linear growth with greater recovery of cortical area (P <.001). Conclusions: Anti-TNF-alpha therapy was associated with improvements in trabecular BMD and cortical structure. Improvements were greater in younger and growing participants, suggesting a window of opportunity for treatment of bone deficits.