Abstract

In children with rheumatic disorders the physiological development of bone strength in response to mechanical loads (the mechanostat model) is frequently impaired. In this population the prolonged inflammatory process and systemic treatment with glucocorticoids (GC) represent the two main risk factors which interfere with the bone remodelling process.

Up to 6% of children with GC-treated rheumatic disorders develop a vertebral fracture in the first 12 months of therapy; children with more severe inflammation and more systemic involvement, such as those with systemic-onset JIA or connective tissue diseases, appear to be at higher risk.

Inflammation exerts a direct and detrimental effect on bone, as generalized bone loss can occur independently from GC exposure. Although cytokines are considered to be the final executors of chronic inflammation on bone, the role of immune cells (e.g. Th17) has recently been highlighted. GC therapy, often at high doses and for prolonged periods, is associated with detrimental effects on bone mass and growth by means of multiple pathogenic mechanisms. By exerting a direct effect on bone cells, GC-induced osteoporosis is characterized by a decreased bone turnover with a disproportionate reduction in bone formation over bone resorption.

The most important clinical outcome arising from lack of bone strength development in childhood rheumatic disorders is represented by fragility fractures. In order to diagnose osteoporosis in children, fracture history should be considered the base of the definition, with additional consideration for the risk factors (sun avoidance, vitamin D deficiency, reduced physical activity), and the overall BMD Z-score trajectory. Several techniques can be used to evaluated bone health in children (e.g. Dual-energy x-ray absorptiometry, peripheral quantitative computerized tomography, and quantitative ultrasound). Dual-energy x-ray absorptiometry (DXA) is the technique currently considered the most appropriate for children because of low radiation, speed, and accuracy.

In rheumatic diseases, a reduction of disease activity represent the mainstay of the treatment, and an anti-inflammatory action of medications such as methotrexate and biological response modifiers has been associated to an improved bone health. The effect of bone-targeted therapy such as bisphosphonates on a developing skeleton has also been explored in pediatric rheumatology. In addition to correct vitamin D deficiency and encourage physical activity, oral or i.v. bisphosphonates can therefore be useful in selected patients, but caution should be used since their long-term effects on a growing skeleton are still unknown.