Serum sclerostin in high-activity adult patients with juvenile idiopathic arthritis.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a disease associated with loss of bone mass, deterioration in bone mass quality and an increased risk of fractures. The objective of this study was to evaluate factors that predict bone mineral density (BMD) alterations in young adult patients with active JIA before and during therapy with tumour necrosis factor α (TNFα) inhibitors. METHODS: Thirty-one patients (twelve males and nineteen females; mean age =25.1 ± 6.1 years) with active JIA (mean Disease Activity Score in 28 joints (DAS28) =6.36 ± 0.64; mean high-sensitivity C-reactive protein (hsCRP) =18.36 ± 16.95 mg/L) were investigated. The control group consisted of 84 healthy individuals matched by sex and age. BMD, bone turnover markers and serum concentrations of soluble receptor activator of nuclear factor κB ligand, osteoprotegerin, dickkopf Wnt signalling pathway inhibitor 1 (Dkk1) and sclerostin were evaluated. RESULTS: Baseline BMD values in the lumbar spine, proximal femur, femoral neck and distal radius were significantly lower in patients with JIA compared to healthy control participants. Baseline sclerostin serum concentrations were significantly higher in patients with JIA compared to control participants. After 2 years of treatment with TNFα inhibitors, BMD was significantly increased in the lumbar spine. This increase correlated with a drop in DAS28 score. A statistically significant correlation between hsCRP and Dkk1 was found at baseline, as well as during the 2-year follow-up period. A significant reduction in serum sclerostin after 1 year of therapy was predictive of a drop in DAS28 score observed with a 1-year delay after reduction of serum sclerostin. CONCLUSION: A significant correlation between the sclerostin serum concentration and the number of tender and swollen joints, but not BMD, supports the hypothesis that chondrocytes and cells of the subchondral bone may contribute to circulating sclerostin in JIA.

The association between lean mass and bone mineral content in the high disease activity group of adult patients with juvenile idiopathic arthritis.

BACKGROUND: The study is aimed to evaluate body composition and bone status in adolescent and adult patients with active juvenile idiopathic arthritis (JIA) untreated with tumor necrosis factor alpha inhibitors. METHODS: Adult patients (12 male and 19 female) with active JIA and 84 healthy age- and gender- matched controls were enrolled into the study. Body composition (tissue mass in grams, lean mass, fat mass and bone mineral content as a fraction of tissue mass) and areal bone mineral density parameters (aBMD) at the lumbar spine, proximal femur, femoral neck, distal radius and total body were assessed using dual energy x-ray absorptiometry (DXA), and correlated with clinical characteristics of the disease and physical performance tests. Disease activity was assessed using high-sensitivity C-reactive protein (hsCRP) and disease activity score 28 (DAS 28). Differences between the groups were tested by t-test, and One-way ANOVA. Correlations were assessed using the Pearson correlation coefficients and multiple linear regression analysis. Significances were counted at the 0.05 level. RESULTS: In patients with clinically active JIA (DAS 28, 6.36 ± 0.64, hsCRP, 18.36 ± 16.95 mg/l), aBMD at all measured sites, bone mineral content (BMC) and lean mass were reduced, and fat mass was increased as compared with healthy controls. Significant negative correlations were observed between BMC and disease duration, use of glucocorticoids (GCs), and fat mass, respectively. A positive correlation was found between BMC and lean mass, and between the body fat fraction and the use of GCs. Using multiple linear regression analysis, lean mass was the only significant predictor of BMC of total body both in men and women, and of BMC of legs (only in men). Lean mass was also the only predicting factor of total proximal femur BMD and femoral neck BMD. No significant correlations have been determined among the body composition parameters and DAS 28 or hsCRP endpoints. CONCLUSIONS: In adult patients with long-term active JIA, lean mass was the main determining factor of total body and leg BMC, and total proximal femur and femoral neck aBMD.

Bone status in adults with early-onset juvenile idiopathic arthritis following 1-year anti-TNFα therapy and discontinuation of glucocorticoids.

Juvenile idiopathic arthritis (JIA) is an inflammatory disease associated with bone loss and low bone mineral density (BMD). The treatment involves disease-modifying antirheumatic drugs, glucocorticoids (GCs) and biological agents. The aim of this study was to evaluate effects of 12-month therapy with the anti-tumor necrosis factor alpha (anti-TNFα) preparations on bone mineral density (BMD) and biochemical turnover markers (BTM) in adult patients with JIA who were previously either treated or not treated with glucocorticoids (GC) and to assess effects of the discontinuation of GCs on their bone status. Nineteen adult patients (12 women, 7 men) aged 18-33 years with active JIA were prospectively enrolled to receive the anti-TNFα therapy (infliximab, etanercept or adalimumab). BMD and BTMs were determined at baseline and 1-year follow-up. The anti-TNFα therapy resulted in a significant reduction in disease activity score 28 (DAS28) and C-reactive protein (CRP) and a significant increase in BMD at the lumbar spine and total body and in serum N-terminal propeptide of type I procollagen (PINP, marker of bone formation). No significant changes in serum beta C-terminal telopeptide of type I collagen (ßCTX, marker of osteoclastic bone resorption) and osteocalcin (marker of bone remodeling) were found. A significant negative correlation was observed between the change in the DAS28, CRP and serum PINP. The change in serum PINP concentrations positively correlated with the change in lumbar spine BMD. A significant increase in serum PINP was observed only in patients discontinuing GCs during the anti-TNFα treatment. After the initiation of the anti-TNFα therapy in young adults with JIA, the increase in new bone formation can be explained by discontinuation of GCs administration as the patients with the largest reduction in DAS28 and CRP probably are the ones most likely to stop GC.

Acute effects of glucocorticoids on serum markers of osteoclasts, osteoblasts, and osteocytes.

The aim of this study was to investigate the acute effects of oral glucocorticoids in doses used in clinical practice on biochemical indices of the function of osteoclasts, osteoblasts, and osteocytes. In 17 adult patients suffering from various medical pathologies requiring systemic steroid therapy that were never before treated with glucocorticoids, glucocorticoid treatment was initiated (mean prednisolone equivalent dose of 23.1 ± 12.7 mg/day, range 10-50). Fasting morning serum concentrations of osteocalcin (OC), amino-terminal propeptide of type I procollagen (PINP), type 1 collagen cross-linked C-telopeptide (ßCTX), soluble receptor activator of nuclear factor kappaB ligand (sRANKL), osteoprotegerin (OPG), sclerostin, Dickkopf-1 (Dkk-1), and high-sensitivity C-reactive protein (hsCRP) were measured at baseline and on three consecutive days. Significant reductions in serum OC, PINP, OPG, sclerostin, and hsCRP were observed during 96 h of glucocorticoid administration, while serum ßCTX showed a significant percentual increase. A significant positive correlation was found between serum concentrations of Dkk-1 and ßCTX after 96 h of treatment with glucocorticoids. A significant drop in serum sclerostin, OPG, and OC observed in this study may reflect the rapid glucocorticoid-induced apoptosis of osteocytes.

Secondary osteoporosis in patients with juvenile idiopathic arthritis.

Bone disease in patients with juvenile idiopathic arthritis (JIA) is associated with focal (joint erosion and juxtaarticular osteopenia) and systemic bone loss (generalized osteopenia or reduction of bone mass density). Pathophysiology of bone loss is multifactorial and involves particularly proinflammatory cytokines and deleterious effects of glucocorticoid therapy. Clinical studies in patients with JIA indicate excessive activation of osteoclastogenesis and reduction of bone formation. Reduction of physical activity, muscle atrophy caused by high disease activity, and compulsory restriction in movements are also associated with bone loss. In patients with JIA, the disease can be complicated by growth cartilage involvement and systemic or local growth retardation. In the absence of preventive measures, fragility fractures can occur even at an early age.