Bone density, structure, and strength in juvenile idiopathic arthritis: Importance of disease severity and muscle deficits

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease (1). Risk factors for low bone mass in JIA include chronic inflammation, delayed pubertal maturation, malnutrition, muscle weakness, physical inactivity, and glucocorticoid therapy (2). The impact of childhood arthritis on bone health may be immediate, resulting in childhood fractures, or it may be delayed, resulting from suboptimal peak bone mass attainment or persistent disease activity. In a population-based study, we demonstrated that childhood arthritis was associated with an elevated risk of fracture in patients older than 10 years (3). Recent investigations using peripheral quantitative computed tomography (pQCT) in JIA demonstrated significant deficits in trabecular volumetric bone mineral density (vBMD), cortical bone mass, and estimates of bone strength in the appendicular skeleton (4–6). Adjustment for low muscle cross-sectional area (mCSA) eliminated the bone deficits in JIA (5), or it paradoxically resulted in the appearance of greater bone mass (4) in children with JIA as compared with healthy controls. The mechanostat theory states that bone adapts to the mechanical or muscle forces to which it is subjected in order to keep the strain on the bone at a constant set point (7). Investigators hypothesized that since muscle and bone deficits in JIA were highly correlated, interventions to improve muscle mass and strength will optimize bone health (4–6). In the study outlining an approach to assessing the “functional muscle–bone unit” in children, muscle mass was first assessed relative to height or age, and bone was then assessed relative to muscle mass (8). This strategy did not account for the strong, independent relationship between bone length and both bone and muscle mass (9). Without adjustment for bone length, the assessment of the functional muscle–bone unit may be confounded in JIA, a disease often complicated by muscle wasting and both systemic and local disturbances of limb growth. In the previous studies of bone health in JIA (4–6), the study patients had high levels of disease activity. With the advent of tumor necrosis factor α (TNFα) inhibitor therapy, greater numbers of children with JIA achieve clinical remission (10) and, potentially, normalization of muscle and bone deficits. Therefore, we used pQCT of the tibia to assess muscle and bone deficits in a population of JIA patients with a spectrum of disease activity as compared with controls, to identify JIA disease characteristics and therapies associated with muscle and bone mass deficits, and to demonstrate that the interpretation of the functional muscle–bone unit in children and adolescents with JIA is dependent on the magnitude of muscle deficits and is sensitive to limb-length adjustment.