Microstructural Vulnerability of the Tibial Tubercle Apophysis During Growth Hormone Therapy: A Multicenter Prospective Cohort Study Using Diffusion Tensor Imaging-MRI.
This study found that growth hormone therapy is associated with increased microstructural changes in the tibial tubercle in children, which may influence fracture risk. Adjusting physical activities during treatment may be advisable.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study measured the microstructural changes in the tibial tubercle of pediatric patients undergoing growth hormone therapy using diffusion tensor imaging. Fifty-three patients, aged ≥6 years, underwent imaging before and at 4, 8, and 12 months after starting therapy. The apparent diffusion coefficient (ADC) increased significantly at 8 months compared to baseline.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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] mm2/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).<h4>Conclusions</h4>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.<h4>Level of evidence</h4>Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Background
This paper addresses the potential impact of growth hormone therapy on tibial tubercle microstructure in children, particularly regarding the risk of avulsion fractures. Previous studies have indicated a connection between rhGH therapy and increased fracture risk, but the underlying mechanisms remain unclear. Understanding these microstructural changes is important for informing clinical practices and managing patient activities during treatment.
Methods
The study utilized a multicenter prospective cohort design involving skeletally immature patients aged ≥6 years who were scheduled to start rhGH therapy. A total of 53 patients underwent diffusion tensor imaging (DTI-MRI) before therapy and at 4, 8, and 12 months post-initiation. Linear mixed-effects models were employed to analyze the effect of time on DTI metrics, adjusting for baseline skeletal age.
Results
The primary endpoint revealed that ADC was significantly higher at 8 months after therapy initiation compared to baseline, with values of 1.61 × 10-3 mm2/sec at 8 months versus 1.52 × 10-3 mm2/sec at baseline (p = 0.041). Additionally, 71% of patients exhibited an increase in ADC following rhGH administration, indicating potential changes in physeal microstructure.
Interpretation
These findings suggest that rhGH therapy may induce transient changes in tibial tubercle microstructure, which could contribute to an increased risk of avulsion fractures. While the statistical significance of the ADC increase is noted, the clinical relevance of these changes remains uncertain, particularly given the small sample size and potential confounding factors. Further research is needed to clarify the implications for clinical practice.
Key findings
- ADC was significantly higher at 8 months compared with baseline (1.61 × 10-3 mm2/sec vs 1.52 × 10-3 mm2/sec, p = 0.041).
- 71% of patients showed an increase in ADC after rhGH administration.
- Greater skeletal age was associated with lower ADC (β = -3.17 × 10-5, p < 0.001).
- Higher fractional anisotropy was associated with greater skeletal age (β = 0.011, p < 0.001).
- Higher tract volume was associated with greater skeletal age (β = 0.106, p = 0.015).
Limitations
- small sample size of n=53
- observational study design limits causal inference
- potential confounding by skeletal age
- no long-term follow-up reported