Glucocorticoid-Associated Osteoporosis in Chronic Inflammatory Diseases: Epidemiology, Mechanisms, Diagnosis, and Treatment

Abstract

Children with chronic illnesses such as Juvenile Idiopathic Arthritis and Crohn's disease, particularly when taking glucocorticoids, are at significant risk for bone fragility. Furthermore, when childhood illness interferes with achieving normal peak bone mass, life-long fracture risk is increased. Osteopenia and osteoporosis, which is increasingly recognized in pediatric chronic disease, likely results from numerous disease- and treatment-related factors, including glucocorticoid exposure. Diagnosing osteoporosis in childhood is complicated by the limitations of current noninvasive techniques such as DXA, which despite its limitations remains the gold standard. The risk:benefit ratio of treatment is confounded by the potential for spontaneous restitution of bone mass deficits and reshaping of previously fractured vertebral bodies. Bisphosphonates have been used to treat secondary osteoporosis in children, but limited experience and potential long-term toxicity warrant caution in routine use. This article reviews the factors that influence loss of normal bone strength and evidence for effective treatments, in particular in patients with gastrointestinal and rheumatologic disorders who are receiving chronic glucocorticoid therapy.

Update on Bone Health in Pediatric Chronic Disease

“…2 Prolonged inflammation exacerbates bone loss. Inflammatory markers, such as TNF-α, interleukin (IL)-1, and IL-6, alter bone modeling and remodeling by inhibition of osteoblast differentiation, impaired collagen synthesis, and promotion of osteoclastogenesis, 5,7 leading to an imbalance favoring resorption. Glucocorticoid use is also associated with decreased BMD 8 and increased fracture risk occurs in those children receiving more than 4 courses or more than 90 days of steroid treatment in a year.…”

“…Nevertheless, studies show that glucocorticoid use itself leads to increased bone resorption via augmentation of the effects of RANKL, decreased OPG function, inhibition of osteoclast apoptosis, and reduced osteoblast number and function. 7 Glucocorticoids can also affect muscle breakdown, the growth hormone–insulinlike growth factor (IGF)-1 axis, and gonadotropin levels, 7 having a cumulative effect of bone resorption.…”

Treatment Perspectives in Crohn’s Disease

“…However, due to multiple side effects and especially the lack of potency to maintain remission [26], it is not reasonable to use glucocorticoids in the long term. Glucocorticoids can worsen diabetes mellitus and osteoporosis [27] and may induce steroid acne, alopecia and depression. Adrenal insufficiency can be avoided by the slow tapering of systemic glucocorticoids.…”

Bone modeling, remodeling, and skeletal health in children and adolescents: mineral accrual, assessment and treatment

“…Conversely, in the long term, the major determinant of damage is impaired bone formation. Osteoblastogenesis is reduced, and apoptosis of osteoblasts and osteocytes is increased11). The osteoblastic function to stimulate the synthesis of type 1 collagen is also impaired.…”