Osteonecrosis in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Abstract

ON among long-term survivors of childhood cancer is rare. However, compared with siblings, childhood cancer survivors have a significantly increased relative rate of ON, particularly those who were older at diagnosis and who received dexamethasone or radiation therapy. Future studies are needed to better delineate our findings, particularly the increased risk after gonadal radiation.

Risk factors for symptomatic osteonecrosis in childhood ALL: A retrospective study of a Slovenian pediatric ALL population between 1970 and 2004

“…In the present cohort age was a strong independent risk factor for ON, which is in accordance with numerous studies (2,4,8,28,29). It has been established that adolescents, particularly those >15 years, are at highest risk for ALL therapy-induced ON.…”

“…All chemotherapeutic agents that are used in the treatment of ALL were found to reduce the number of osteoblast-like cells in vitro (5), and combinations of different agents had more toxic effects compared with individual agents (30). GCs were found to exhibit the strongest risk of ON in the clinical setting during ALL therapy (2), although MTX and alkylating agents were also indicated to be associated with ON risk in certain studies (2,3,6). Therefore, we reviewed all used protocols to detect differences in administration schedule and doses of GC and MTX.…”

“…Although non-traumatic ON is rare in young people, it has been reported increasingly in children treated for acute lymphoblastic leukemia (ALL), as ALL survival rates continue to improve (1). The symptoms of ON are highly variable, ranging from mild discomfort to decreased mobility, severe pain and articular collapse (2). Although up to 25% of children treated for ALL exhibit radiographic evidence of osteopenia (3) and one-third of ALL patients develop symptomatic ON (1), the majority of patients are asymptomatic, some showing the spontaneous regression or even complete resolution of the disorder (1).…”

“…Although up to 25% of children treated for ALL exhibit radiographic evidence of osteopenia (3) and one-third of ALL patients develop symptomatic ON (1), the majority of patients are asymptomatic, some showing the spontaneous regression or even complete resolution of the disorder (1). Due to heterogenous diagnostic criteria, the reported incidence of ON varies widely in children with cancer; between 0.3 and 9% (2,4). The pathogenesis of ON is complex and includes the enhanced differentiation of mesenchymal stem cells (MSCs) into lipocytes at the expense of osteogenesis, as well as damage to the venous system, vascular stasis and ischemia (1).…”

6-MP based maintenance therapy of childhood ALL in Slovenia: a retrospective study from 1970 to 2004

“…This is in accordance with numerous studies. 18,19 Adolescents are at highest risk for ALL therapy induced osteonecrosis due to their grater vulnerability or rapid bone growth in this period.20 Among drugs used for childhood ALL treatment glucocorticoids were identified as a main risk factor for osteonecro- sis,18 although other therapeutic agents such as MTX18 and 6-MP19 have been associated with bone morbidity during ALL treatment.…”