Glucocorticoid-Induced Osteoporosis: Why Kids Are Different

Abstract

Glucocorticoids (GC) are an important risk factor for bone fragility in children with serious illnesses, largely due to their direct adverse effects on skeletal metabolism. To better appreciate the natural history of fractures in this setting, over a decade ago the Canadian STeroid-associated Osteoporosis in the Pediatric Population (“STOPP”) Consortium launched a 6 year, multi-center observational cohort study in GC-treated children. This study unveiled numerous key clinical-biological principles about GC-induced osteoporosis (GIO), many of which are unique to the growing skeleton. This was important, because most GIO recommendations to date have been guided by adult studies, and therefore do not acknowledge the pediatric-specific principles that inform monitoring, diagnosis and treatment strategies in the young. Some of the most informative observations from the STOPP study were that vertebral fractures are the hallmark of pediatric GIO, they occur early in the GC treatment course, and they are frequently asymptomatic (thereby undetected in the absence of routine monitoring). At the same time, some children have the unique, growth-mediated ability to restore normal vertebral body dimensions following vertebral fractures. This is an important index of recovery, since spontaneous vertebral body reshaping may preclude the need for osteoporosis therapy. Furthermore, we now better understand that children with poor growth, older children with less residual growth potential, and children with ongoing bone health threats have less potential for vertebral body reshaping following spine fractures, which can result in permanent vertebral deformity if treatment is not initiated in a timely fashion. Therefore, pediatric GIO management is now predicated upon early identification of vertebral fractures in those at risk, and timely intervention when there is limited potential for spontaneous recovery. A single, low-trauma long bone fracture can also signal an osteoporotic event, and a need for treatment. Intravenous bisphosphonates are currently the recommended therapy for pediatric GC-induced bone fragility, typically prescribed to children with limited potential for medication-unassisted recovery. It is recognized, however, that even early identification of bone fragility, combined with timely introduction of intravenous bisphosphonate therapy, may not completely rescue the osteoporosis in those with the most aggressive forms, opening the door to novel strategies.

Bone Health in Children with Rheumatic Disorders: Focus on Molecular Mechanisms, Diagnosis, and Management

“…VFs are the clinical hallmark of paediatric GC-induced osteoporosis. They occur early during GC treatment, are frequently asymptomatic, and may remain undetected if routine monitoring is not performed [ 108 ]. The risk of fractures rapidly decreases after GC therapy cessation; nevertheless, it remains above the baseline [ 94 ].…”

“…The peripubertal period is a critical moment in determining whether a child has sufficient residual growth potential to allow this vertebral reshaping. However, it is known that older children with less residual growth potential, children with poor growth, and children with ongoing risk factors (GC use, poorly controlled underlying disease, severe vertebral collapse and immobilization) have less potential for spontaneous recovery [ 108 ].…”

Understanding and Managing Corticosteroid-Induced Osteoporosis

“…IV bisphosphonates are the mainstay of therapy, but studies are underway investigating the efficacy of denosumab in this population. 81 …”

Pathogenesis of Musculoskeletal Deficits in Children and Adults with Inflammatory Bowel Disease

“…Chronic glucocorticoid exposure can lead to muscle atrophy and glucocorticoid-induced osteoporosis with an increased risk of fragility fractures [ 61 , 62 , 63 ]. In children, glucocorticoid exposure can also lead to delayed pubertal development and inhibition of linear growth [ 64 , 65 ]. Given that linear growth and pubertal development are also major drivers of bone development during childhood, it is not surprising that factors that inhibit growth and puberty lead to inadequate bone accrual.…”