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

Abstract

Bone is an extremely dynamic and adaptive tissue, whose metabolism and homeostasis is influenced by many different hormonal, mechanical, nutritional, immunological and pharmacological stimuli. Genetic factors significantly affect bone health, through their influence on bone cells function, cartilage quality, calcium and vitamin D homeostasis, sex hormone metabolism and pubertal timing. In addition, optimal nutrition and physical activity contribute to bone mass acquisition in the growing age. All these factors influence the attainment of peak bone mass, a critical determinant of bone health and fracture risk in adulthood. Secondary osteoporosis is an important issue of clinical care in children with acute and chronic diseases. Systemic autoimmune disorders, like juvenile idiopathic arthritis, can affect the skeletal system, causing reduced bone mineral density and high risk of fragility fractures during childhood. In these patients, multiple factors contribute to reduce bone strength, including systemic inflammation with elevated cytokines, reduced physical activity, malabsorption and nutritional deficiency, inadequate daily calcium and vitamin D intake, use of glucocorticoids, poor growth and pubertal delay. In juvenile arthritis, osteoporosis is more prominent at the femoral neck and radius compared to the lumbar spine. Nevertheless, vertebral fractures are an important, often asymptomatic manifestation, especially in glucocorticoid-treated patients. A standardized diagnostic approach to the musculoskeletal system, including prophylaxis, therapy and follow up, is therefore mandatory in at risk children. Here we discuss the molecular mechanisms involved in skeletal homeostasis and the influence of inflammation and chronic disease on bone metabolism.

Prognostic value of the systemic immuno-inflammatory index in critically ill patients with vertebral fractures

“…Inflammation plays a crucial role in the progression, pathogenesis, and prognosis of vertebral fractures. [ 20 , 21 ] In this large-scale study, the SII was identified as an independent risk factor for all-cause mortality among patients with vertebral fractures. The results showed a significant association between high SII levels and increased all-cause mortality in these patients, even after adjusting for multiple variables.…”

Bone Mineral Density and Serum 25OHD in Children and Adolescents With Juvenile Idiopathic Arthritis

“…All JIA patients in our study fulfilled the indications for performing DXA as the patients with JIA had at least 1 risk of developing low bone mass including chronic inflammation, joint destruction, and glucocorticoids treatment. 16,37…”

“…All JIA patients in our study fulfilled the indications for performing DXA as the patients with JIA had at least 1 risk of developing low bone mass including chronic inflammation, joint destruction, and glucocorticoids treatment. 16,37 The BMD results were analyzed by using the Prodigy Encore Software (version 7.53, standard scan mode). Measurements included BMD of the lumbar spines (L2-L4) (BMDLS) and BMD of the total body (BMDTB).…”

“…Bone mineral content and density references according to age, sex, and race are available for children older than 5 years. 16,17 Growth restriction has been described in patients with JIA. 18 Measurement of bone mineral density (BMD) by DXA in children and adolescents is affected by height.…”

Markers associated with the development of osteoporosis in children with juvenile idiopathic arthritis

“…Ho wever, it should be noted that the prevalence of JIA has not changed significantly over the past 5 years [1,2]. It has been demonstrated that the development of systemic autoimmune and inflammatory diseases, including JIA, is accompanied by a decrease in bone mineral density and an increased risk of bone fractures during childhood [3,4]. A decrease in bone mineral density is observed in all parts of the skeleton in children and adolescents with JIA, and up to 50 % of adults with a history of JIA [5].…”