Strong Association Between Growth Hormone Therapy and Proximal Tibial Physeal Avulsion Fractures in Children and Adolescents

Abstract

Background: Published literature describes slipped capital femoral epiphysis as a complication of recombinant human growth hormone (rhGH) therapy that may be related to decreased physeal strength. The purpose of the current investigation was to utilize a case-control study design to determine whether a greater proportion of pediatric patients sustaining physeal avulsion fractures of the proximal tibia were undergoing rhGH therapy at the time of injury compared with a cohort of matched controls. Methods: A case-control design study design was utilized. Patients 4 to 18 years of age with proximal tibial physeal avulsion fractures (cases) or midshaft tibial fractures (controls) at our institution from February 1, 2016, to May 4, 2023, were identified. Cases and controls were matched 1:1 on the basis of age (within 1 year), sex, and body mass index (within 3 kg/m2). A total of 132 patients were included in the analysis (mean age, 13 ± 2 years). rhGH exposure was compared using conditional logistic regression with Firth correction. Results: We found that 11% of the patients with a proximal tibial physeal avulsion fracture were on rhGH therapy at the time of injury compared with 0% of patients with midshaft tibial fractures (odds ratio [OR], 15.0; 95% confidence interval [CI], 1.8 to 1,946.7; p = 0.007). There was no significant difference in the proportion of sports-related injuries between cases (70%) and controls (67%) (OR, 1.15; 95% CI, 0.55 to 2.39; p = 0.85). Among subjects with proximal tibial avulsion fractures, the proportion requiring surgery did not differ significantly between patients receiving and those not receiving rhGH therapy (43% versus 41%, respectively; p = 0.99). Conclusions: This study demonstrates that the proportion of subjects who sustained proximal tibial physeal avulsion fractures and were receiving recombinant human growth hormone therapy at the time of injury was significantly greater than that of an age, sex, and body mass index-matched control group with midshaft tibial fractures (11% versus 0%, respectively, representing 15-times greater odds of exposure). This quantifies a previously unreported serious orthopaedic complication associated with rhGH therapy. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.