In our study of TNFα blocker naïve patients with JIA, a reduction of aBMD at all measured areas of the skeleton, except the distal radius T-score was observed. Decreased aBMD has been reported also in children and adolescents with JIA at all skeletal sites. Zak et al. described low bone mass density in LS spine and hips in 42-52% of adult JIA patients, both male and female . In our study, a statistically significant dependence was seen between bone mass density parameters (BMD in g/cm2 and T-score in the area of proximal femur, femoral neck and trochanter, BMD in g/cm2 of distal radius and total body T-score) and the lean mass. Significant correlations were observed between BMC and disease duration, GCs usage and lean mass, respectively. Lean mass was the only determining factor of total proximal femur BMD and femoral neck BMD. Also, lean mass was the main determinant of the total body BMC both in women and men, and also of the leg BMC in men. This is in good agreement with the observations on body composition in non-corticosteroid–treated postpubertal women and in prepubertal children with JIA [15–17].
The differences between body composition of total body and legs in the subgroup of women with JIA treated and not treated with GCs indicate a negative effect of GCs on the lean mass and BMC, and the positive effect on fat tissue. This is in good agreement with several cross-sectional and longitudinal studies demonstrating substantial effects of GCs on muscle atrophy and body composition in patients with medical illnesses such as Crohn’s disease, multiple sclerosis, systemic lupus erythematosus, glucocorticoid-sensitive nephrotic syndrome and post-renal transplantation [18–23]. The significant positive correlation between the activity of the disease and GC use could be explained by the necessity of GC therapy in patients with severe course of disease. However, while 9 out of 19 women patients were on GC therapy, the BMC fraction was significantly predicted by GC use rather than by DAS28. The importance of lean mass is further supported by the significant correlation between disease duration and increase of fat mass and reduction of bone and lean mass and deteriorated physical performance of legs evaluated using the chair test. In a study where lean mass and cortical and trabecular bone forearm BMD were measured using peripheral quantitative computed tomography, JIA patients had significantly reduced muscle cross-sectional area and this reduction significantly correlated with muscle strength and bone geometry abnormalities and, particularly, with reduced thickness of the cortical bone . Similar conclusions were derived from the measurement of muscle and bone mass of the tibia . Prolonged exposure to GCs can lead to muscle atrophy.
The aforementioned results support the hypothesis that muscles (at least in adults) play a dominant role in the synchronization of muscle and bone mass . This closely linked function and form of both tissues may be, from the embryonic development to the old age, influenced by genetic dispositions, morphogenic factors, sex steroids and, in adulthood, particularly mechanical signals , inter alia through myokines (myostatin, leukemia inhibitory factor, interleukin 6, interleukin 7, insulin-like growth factor 1, fibroblast growth factor 2, follistatin-like protein and irisin) . The myostatin/activin signaling pathway may be involved in both muscle and bone coordination . Increased cytokine production during long-lasting inflammations induces protein degradation, inhibits myocyte differentiation and induces apoptosis of myocytes and myopathy . In JIA, inflammation may be, through muscular mass reduction, responsible also for reduced bone mass. As muscles are the main source of myostatin and the administration of glucocorticoids is associated with an increased production of myostatin, muscular atrophy and increased secretion of myostatin in active JIA further suppresses new bone formation and induces reduction of BMD [31, 32]. The cause of the myopathic condition is not necessarily limited to the inflammatory cytokines – it could also involve GCs and the lower physical activity in JIA patients [24, 30]. Glucocorticoids not only decrease muscle anabolism by inhibiting amino acid transport into the muscle , but also increase muscle catabolism . GCs play a key role in inducing proteolysis in acute inflammatory states via the autophagy and the ubiquitin–proteasome pathways .
Several limitations of the study must be taken into account. First, the sample size was not large enough to make definite conclusions by multiple logistic regression analysis. Secondly, the results do not allow for an assessment of the association of changes in tissue composition with the risk of fracture . The established correlations between mass and bone unit may be influenced by genetic factors  and individual differences in physical activity and diet [37, 38] that were not controlled in this study. Also, individual patient susceptibility to adverse effects of GCs depends on GC dose, duration of therapy, GC receptor saturation levels and GC receptor gene polymorphisms . The cross-sectional nature of the study does not allow for a more accurate assessment of the muscular-bone unit relationship in individual patients and the disease activity.
The results of this study show significant effects of both the disease and GC therapy on aBMD and body composition in patients with JIA and support the hypothesis of the dominant role of muscles in the synchronization of muscular and bone mass.