Microstructural Vulnerability of the Tibial Tubercle Apophysis During Growth Hormone Therapy

Background: Tibial tubercle avulsion fractures occur in pediatric patients during periods of physeal vulnerability and have been associated with exposure to growth hormone therapy (rhGH). Diffusion tensor imaging-magnetic resonance imaging (DTI-MRI) can detect alterations in physeal microarchitecture by characterizing water diffusion along the organized cartilaginous columns of the physis. This study leveraged DTI-MRI to evaluate whether initiation of rhGH therapy is associated with temporally distinct changes in tibial tubercle physeal microstructure, which could potentially predispose children and adolescents to tibial tubercle avulsion fractures. Methods: Patients were recruited as part of a multicenter prospective cohort study. Skeletally immature patients aged ≥6 years scheduled to initiate rhGH therapy underwent DTI-MRI before rhGH administration and 4, 8, and 12 months after therapy initiation. Linear mixed-effects models were used to assess the effect of time on DTI metrics, with Dunnett-adjusted post hoc comparisons. Baseline skeletal age was included as a covariate. Results: Fifty-three patients were enrolled; 68% were male, 83% were White, and the mean skeletal age at therapy initiation was 10 ± 3 years. The apparent diffusion coefficient (ADC) in the tibial tubercle increased in 71% of patients after rhGH administration, with the maximum increase at 8 months. In adjusted mixed-effects models, ADC was significantly higher at 8 months compared with baseline (1.61 × 10 −3 [95% confidence interval (CI): 1.55 to 1.68 × 10 −3 ] versus 1.52 × 10 −3 [95% CI: 1.46 to 1.58 × 10 −3 ] mm 2 /sec, p = 0.041). Greater skeletal age was independently associated with lower ADC (β = −3.17 × 10 −5 , p < 0.001), higher fractional anisotropy (β = 0.011, p < 0.001), and higher tract volume (β = 0.106, p = 0.015). Conclusions: DTI-MRI identified temporally distinct microstructural changes at the tibial tubercle following rhGH initiation. The increase in ADC suggests transient physeal expansion and remodeling within at least the first 8 months of treatment, during a time in which ADC would typically be decreasing with normal skeletal maturation. This study therefore provides mechanistic insight into the reported association between rhGH therapy and tibial tubercle avulsion fractures. Adjusting impact sports and activities during this vulnerable time should be strongly considered. Level of Evidence: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.