Diagnosis, Follow-Up and Therapy for Secondary Osteoporosis in Vulnerable Children: A Narrative Review

Abstract

By definition, children constitute a vulnerable population, especially when they are chronically ill and/or disabled. A characteristic of chronically ill and disabled children is that they also suffer from indirect effects of their disease, such as immobilization, chronic inflammation, reduced time outdoors in the sun, osteotoxic effects of disease-targeted therapy (like glucocorticoids), and poor nutrition. All these factors may lead to bone fragility due to secondary osteoporosis, a co-morbidity that may be overlooked in the context of serious underlying diseases. The ultimate goal of osteoporosis diagnosis and monitoring in this setting is the early identification, prevention, and treatment of low-trauma long bone and vertebral fractures; indeed, vertebral fractures are a frequently under-diagnosed manifestation of overt bone fragility in this context. Efforts to prevent first-ever fractures are also meritorious, including encouragement of weight-bearing activities, optimization of nutritional status, including calcium and vitamin D supplementation, and the diagnosis and treatment of delayed growth and puberty; however, these conservative measures may be insufficient in those at high risk. Numerous natural history studies have shown that vertebral fractures are more common than non-vertebral (i.e., long bone) fractures in at-risk children. Not surprisingly, the cornerstone of secondary osteoporosis monitoring is lateral spine imaging for the early detection of vertebral collapse. Although dual-energy x-ray absorptiometry (DXA) is the gold standard to measure bone mineral density, digital X-ray radiogrammetry may be used as a surrogate measure of bone strength if dual-energy x-ray absorptiometry is not available. In the event that preventive measures fail, treatment with bisphosphonates may be appropriate. Typically, treatment with intravenous bisphosphonates is reserved for children with overt bone fragility and limited potential for spontaneous recovery. However, there is increasing attention to very high-risk children, such as boys with Duchenne muscular dystrophy, who may benefit from bisphosphonate therapy prior to first-ever fractures (given their high fracture frequency and essentially absent potential for spontaneous recovery). This article provides a contemporary overview of the definition and diagnosis of osteoporosis in children with chronic illness, along with the approach to monitoring those at risk and the evidence for currently recommended intervention strategies.