Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy

Abstract

Background Childhood cancer survivors treated with cranial or total body irradiation (TBI) are at risk for growth hormone deficiency (GHD). Recombinant growth hormone (rhGH) therapy is associated with slipped capital femoral epiphysis (SCFE). We compared the incidence of SCFE after TBI versus cranial irradiation (CI) in childhood cancer survivors treated with rhGH. Procedure Retrospective cohort study (1980–2010) of 119 survivors treated with rhGH for irradiation-induced GHD (56 TBI; 63 CI). SCFE incidence rates were compared in CI and TBI recipients, and compared with national registry SCFE rates in children treated with rhGH for idiopathic GHD. Results Median survivor follow-up since rhGH initiation was 4.8 (range 0.2–18.3) years. SCFE was diagnosed in 10 subjects post-TBI and none after CI (P < 0.001). All 10 subjects had atypical valgus SCFE, and 7 were bilateral at presentation. Within TBI recipients, age at cancer diagnosis, sex, race, underlying malignancy, age at radiation, and age at initiation of rhGH did not differ significantly between those with versus without SCFE. The mean (SD) age at SCFE diagnosis was 12.3 (2.7) years and median duration of rhGH therapy to SCFE was 1.8 years. The SCFE incidence rate after TBI exposure was 35.9 per 1,000 person years, representing a 211-fold greater rate than reported in children treated with rhGH for idiopathic GH deficiency. Conclusions The markedly greater SCFE incidence rate in childhood cancer survivors with TBI-associated GHD, compared with rates in children with idiopathic GHD, suggests that cancer treatment effects to the proximal femoral physis may contribute to SCFE.

Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency

“…Treatment can often be reinstituted at lower doses without return of symptoms. with IGHD (18.3) and ISS (14.5) compared to those with GHD due to intracranial neoplasms (86.1), craniopharyngioma (120), or after stem cell transplantation [119,120] . The median duration from onset of GH therapy to SCFE ranges from 0.4 to 2.5 years.…”

Musculoskeletal complications following total body irradiation in hematopoietic stem cell transplant patients

“…The incidence is estimated to be 10.8 per 100,000 children and is more common in males, blacks, and pacific islanders . It is associated with obesity, growth spurts, and endocrine disorders such as hypothyroidism, hypogonadism, and panhypopituitarism . SCFE is also a known complication in HSCT patients and is likely related to the systemic effects of chemotherapy, TBI, and GH replacement …”

“…There are several key differences between SCFEs in HSCT/TBI patients and those occurring in the general population . The average age at the time of SCFE presentation in the general population is 13.5 years, with the majority occurring in pubertal children .…”

“…Many of these adverse effects involve the musculoskeletal system and include short stature, osteonecrosis, slipped capital femoral epiphysis (SCFE), and the development of benign (e.g., osteochondromas) and malignant tumors (e.g., radiation‐induced sarcomas) . In this review, we hope to bring attention to these important late effects.…”

Total-body irradiation produces late degenerative joint damage in rats

“…In the musculoskeletal system, the clinical concerns in children have been altered growth, bone fracture, spinal deformity, osteochondroma, and secondary bone malignancies (Leiper et al 1987; Chemaitilly et al 2007; Shido et al 2012). Metaphyseal trabecular bone changes, osteonecrosis of the femoral head, growth plate cartilage manifestations, including slipped capital femoral epiphysis, and platyspondylyl of the spine have been well studied and documented (Kaste et al 2004; Damron et al 2008; Damron et al 2009; Miyazaki et al 2009; Pritchard et al 2010; Mostoufi-Moab et al 2012; Mostoufi-Moab et al 2013). …”