No Association Between Growth Hormone Therapy and Upper Extremity Physeal Tension Injuries: A Matched Case-control Study
Authors: Jones Ruth H. , Beber Samuel A. , Adhiyaman Akshitha , Tracey Olivia C. , Lijesen Emilie , Green Daniel W. , Fabricant Peter D. 
Published: September 2024

Background
Recent evidence has identified a strong association between growth hormone therapy and physeal injuries in the lower extremity; however, few studies have investigated this association in the upper extremity.

Questions/purposes
(1) Do pediatric patients with physeal tension injuries of the shoulder and elbow have higher odds of having exposure to recombinant growth hormone therapy than matched controls? (2) Are the odds of having exposure to recombinant growth hormone therapy in physeal tension injuries different when stratified by shoulder and elbow injuries?

Methods
Using a matched case-control study design, patients between 4 and 18 years of age treated at a large, urban, academic center from February 1, 2016, to November 6, 2023, were identified by ICD-10 codes using EPIC SlicerDicer, an electronic medical record–based data mining tool. Patients diagnosed with physeal tension injuries in the shoulder or elbow were included in the case group, and those with midshaft radius, metaphyseal radius, or both-bone forearm fractures were included in the control group. A total of 618 patients with physeal injuries and 1244 with non-physeal fractures were identified and screened for inclusion. After further chart review to confirm diagnoses, 46% (283) of patients with physeal injuries and 54% (670) of patients with non-physeal fractures were included. A further 6% (16) of patients with physeal injuries and 2% (15) of patients with non-physeal injuries were excluded due concomitant dislocations or missing data, resulting in 267 eligible patients with physeal injuries and 655 eligible patients with non-physeal fractures. Two patients with concurrent elbow and shoulder physeal injuries were additionally excluded from stratified analyses. Patients with physeal injuries and non-physeal fractures were 1:1 matched by age ± 0.5 years, sex, and BMI ± 2 kg/m2. In all, 522 patients were included in the analysis, including 261 patients with physeal injuries and 261 with non-physeal fractures. The mean ± SD ages for both patient groups was 13 ± 2 years (p = 0.44), 88% (229 of 261) of all participants were male, and the mean BMIs were 19.9 ± 3.0 kg/m2 and 19.4 ± 3.0 kg/m2 (p = 0.11), respectively. Growth hormone exposure was compared between patients with physeal injuries and non-physeal fractures using a conditional logistic regression model.

Results
Overall, 4% (10 of 261) of patients with physeal injuries had exposure to growth hormone therapy as compared with 2% (4 of 261) of patients with non-physeal fractures (OR 2.5 [95% confidence interval 0.8 to 8.0]). Subgroup analyses of shoulder and elbow injuries demonstrated no difference in growth hormone exposure between patients with physeal injuries and non-physeal fractures (OR 2 [95% CI 0.4 to 10.2] and OR 3 [95% CI 0.6 to 14.9], respectively).

Conclusion
In light of these results, clinicians may not need to advise precaution against sports or other activities that put the upper extremity physes under stress when treating patients with growth hormone supplementation therapy. Future multicenter studies, however, are indicated to further investigate for the existence of any subtle association between growth hormone therapy and upper extremity physeal injuries relative to the large association previously noted in the lower extremity in pediatric and adolescent patients.

Level of Evidence
Level III, therapeutic study.