Osteoporosis due to Glucocorticoid Use in Children with Chronic Illness

Abstract

Osteoporosis is increasingly recognized as a complication of chronic childhood illnesses, particularly when glucocorticoids (GCs) are necessary for treatment. Elucidation of the mechanisms leading to bone fragility in these settings requires disentanglement of the relative contributions of myriad risk factors, including disease activity, muscle weakness, immobilization, delayed growth and puberty, compromised nutrition, and osteotoxic medications. Over the years, bone mass and density evaluations by dual energy X-ray absorptiometry (DXA) have become popular for assessing bone health in children; however, such measurements are difficult to interpret because of the confounding effect of bone size and the lack of DXA-based densitometric criteria for defining osteoporosis in childhood. Recently, a new diagnostic approach for evaluation of densitometric data in children has been suggested, driven by Frost’s mechanostat theory. A diagnostic algorithm based on the mechanostat theory of bone-muscle development is proposed for the characterization of bone disease in children with chronic illness. In addition to DXA-based assessments, techniques such as peripheral quantitative computerized tomography and ilial histomorphometry, for which there are pediatric reference data, are gaining ground in the characterization of skeletal changes due to chronic illness. Although these diagnostic techniques expand our understanding of osteoporosis in children, they do not replace clinical assessment. Concrete clinical evidence for GC-induced bone fragility can be seen in spinal changes due to vertebral compression, with spinal morphometry emerging as an essential, but frequently overlooked, tool in the evaluation of children’s bone health. Presently, osteoporosis treatment in the chronic illness setting remains experimental and should be restricted to clinical studies. Following an understanding of the natural history of GC-induced osteoporosis in children, randomized, placebo-controlled prevention and intervention trials will be the next step toward the development of clinical practice guidelines.

An Official American Thoracic Society Clinical Practice Guideline: Classification, Evaluation, and Management of Childhood Interstitial Lung Disease in Infancy

“…If a clinician elects to initiate a trial of immunosuppressive therapy, the patient should be closely monitored for side effects. This may include bone density scanning, serial growth measurements, and ophthalmologic screening in children receiving chronic corticosteroids (199,200), or periodic complete blood counts and ophthalmologic evaluations in children receiving chronic hydroxychloroquine (201,202).…”

Skeletal Fragility in Children with Chronic Disease

“…Skeletal fragility in childhood due to chronic disease is a systemic disorder of abnormal bone growth leading to abnormal bone mass, geometry and microarchitecture, which can lead to pathological fractures in childhood or later on in life [1,2]. Linear growth is a major driver of periosteal apposition by which bones can increase in length and width and, therefore, improvement of bone strength [3].…”

Observer agreement in pediatric semiquantitative vertebral fracture diagnosis

“…Vertebral fractures are increasingly recognized as an important clinical consequence of osteoporosis in children and adolescents, particularly those treated with glucocorticoids [17][18][19]. There is not yet an accepted morphometric approach to radiological assessment, although several research groups have developed methodologies for their own use [20][21][22].…”