ESPE Abstracts (2019) 92 S2.3

Glucocorticoid-Induced Osteoporosis in Children: Targeting the Spine in Osteoporosis Diagnosis, Monitoring and Treatment

Leanne M. Ward


University of Ottawa, Ottawa, Ontario, Canada


Despite significant advances in the medical management of childhood diseases, glucocorticoids (GCs) continue to be the mainstay of therapy for numerous serious conditions, including hematological malignancies, Duchenne muscular dystrophy (DMD) and inflammatory disorders. In order to understand the natural history of bone development in GC-treated children, a pan-Canadian longitudinal observational research study called "STOPP" (STeroid-induced Osteoporosis in the Pediatric Population) was launched in the last two decades. The STOPP study revealed a number of key biological principles about pediatric GC-induced osteoporosis (GIOP); among the most important was that vertebral fractures are the clinical signature of GIOP in children, an observation which unveiled the vulnerability of the pediatric trabecular-rich spine to the toxic effects of GCs.

By showing that vertebral fractures in GIOP are linked to biologically logical predictors including back pain, bone mineral density and an increased risk of future fractures, the STOPP Consortium validated that > 20% loss of vertebral height ratio defines a vertebral fracture in children, a decision that can be aided in equivocal cases by qualitative signs of vertebral fracture such as loss of endplate parallelism, endplate interruption and in older children, anterior cortical buckling. Reshaping of vertebral fractures (i.e. restoration of normal vertebral dimensions) is a key sign of recovery from GIOP, a phenomenon that occurs in the absence of osteoporosis therapy among children with significant residual growth potential, and transient GC exposure (such as younger children with leukemia). On the other hand, persistent bone health threats (such as in DMD), or GC exposure in older children with less growth potential, both mitigate the potential for vertebral body reshaping and can lead to permanent vertebral deformity if treatment is not initiated in a timely fashion. Current evidence suggests this is an important adverse outcome of pediatric GIOP, given observations that adults with vertebral fractures due to osteoporosis have reduced pulmonary function compared to those without.

Together, these findings underscore the importance of early identification and treatment of vertebral fractures in children at risk for permanent vertebral deformity, either due to older age or aggressivity of the GC exposure. Intravenous (IV) bisphosphonate therapy is a safe and effective first-line therapy for treatment of GC-induced vertebral fractures. However, IV bisphosphonates do not completely rescue the phenotype in the most aggressive forms of GIOP, an observation that opens the door to novel strategies.

Disclosures: Previously participated in a clinical trial with Merck. Currently a consultant to and participating in clinical trials with Novartis and Amgen, with funding to Dr. Ward's institution.

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