Growth hormone changes bone geometry and body composition in patients with juvenile idiopathic arthritis requiring glucocorticoid treatment: a controlled study using peripheral quantitative computed tomography.

Osteopenia and growth retardation have been described in children with chronic arthritis. GH has an impact on both. In the present controlled study, we used peripheral quantitative computed tomography to evaluate forearm bone mass, density, and geometry as well as forearm muscle and fat area in 17 patients with juvenile idiopathic arthritis (JIA) receiving treatment with GH for 3.8 +/- 1.1 yr compared with an untreated age- and sex-matched control group (n = 17). All patients had a mean age of 15.3 +/- 2.5 yr and a mean duration of illness of 8.2 +/- 4.4 yr. Height, weight, body mass index, bone parameters, and muscle area were significantly decreased in both groups compared with those in healthy age-matched children. Compared with untreated JIA patients, GH-treated JIA patients had significant higher bone mineral content as well as total cross-sectional area (CSA), cortical CSA, and muscle CSA. Fat CSA was lower in the GH-treated group. A significant difference between groups for height-corrected cortical and muscle areas was only seen in male patients. Cortical CSA relative to muscle CSA was not different between groups. These findings are compatible with an anabolic effect of GH on muscle and bone development.

GH therapy in juvenile chronic arthritis: results of a two-year controlled study on growth and bone.

Disturbance of growth frequently occurs in children suffering from juvenile chronic arthritis (JCA). Recognition of growth impairment is important because reduced final height is one of the permanent consequences. The aim of this study was to evaluate the efficacy and safety of human GH (hGH) in growth-retarded prepubertal children with JCA. Thirty-five children were tested for GH deficiency (GHD) and randomly assigned to a study and an untreated control group; five were GH deficient and were part of the GHD group. All received glucocorticoids. The study group was treated with 1 IU/kg BW.wk hGH; the GHD group was given 0.5 IU. During 2 yr of hGH treatment growth velocity and height SD score increased compared with baseline values. There was a marked increase in growth velocity in the treated groups, but also some increase in the control group. Plasma levels of IGF-I and IGF-binding protein-3 increased with GH treatment. These results suggest that hGH might be useful in the treatment of growth impairment in JCA. GH may counteract the adverse effects of glucocorticoid therapy, but its effect is dependent on the disease activity. Long-term controlled studies are needed to determine the risks and benefits of GH therapy in JCA.

Total pubertal growth in patients with juvenile idiopathic arthritis treated with growth hormone: analysis of a single center.

OBJECTIVES: Growth failure is a permanent sequelae in juvenile idiopathic arthritis (JIA). The aim of the study was to compare pubertal growth in control and growth hormone (GH) treated JIA subjects. DESIGN: 64 children with JIA at a mean age of 10.38 ± 2.80 years were enrolled and followed until final height (measured in standard deviation (SD) scores). 39 children (20 m) received GH therapy and 24 (9 m) served as controls. GH dose was 0.33 mg/kg/week. Linear regression analysis was performed to identify factors influencing total pubertal growth. RESULTS: Mean total pubertal growth was 21.1 ± 1.3 cm (mean ± SD) in GH treated JIA patients and 13.8 ± 1.5 cm in controls. Final height was significantly higher with GH treatment (-1.67 ± 1.20 SD) compared to controls (-3.20 ± 1.84 SD). Linear regression model identified age at onset of puberty (ß=-4.2,CI: -5.9, -2.6 in controls and ß=-2.3,CI: -3.6, -1.1 in GH treated) as the main factor for total pubertal growth. Final height SDS was determined by the difference to target height at onset of puberty (ß=-0.59;CI: -0.80, -0.37 in controls and ß=-0.30,CI: -0.52, -0.08 in GH treated), age at onset of puberty (ß=0.47;CI:0.02,0.93 in controls and 0.23;CI: -0.00,0.46 in GH treated) and height gain during puberty (ß=0.13;CI:0.05,0.21 in controls and ß=0.11;CI:0.07,0.16 in GH treated). CONCLUSION: Total pubertal growth in JIA patients treated with GH was increased by a factor of 1.5 greater in comparison to controls leading to a significantly better final height. To maximize final height GH treatment should be initiated early to reduce the height deficit at onset of puberty.

Musculoskeletal and functional muscle-bone analysis in children with rheumatic disease using peripheral quantitative computed tomography.

Bone demineralization is a severe complication of juvenile idiopathic arthritis (JIA) and other rheumatic diseases. To identify patients, who are at risk of bone disease, musculoskeletal analysis is performed. Furthermore, a more functional approach is needed to assess, whether bone strength is adequate for muscle force and whether muscle force is adequate for body size. In patients with a chronic disease it is most important to differentiate between primary bone problems and those that are secondary to low muscle force. To implement this approach, we measured musculoskeletal parameters of the radius in 94 patients with juvenile idiopathic arthritis of different subtypes and connective tissue disease using peripheral quantitative computed tomography. The four groups consisted of patients with oligoarticular (n = 31), polyarticular (n = 27), systemic JIA (n = 20) and connective tissue disease (CTD) (n = 16). All patients with systemic JIA and CTD and 56% of the patients with polyarticular JIA were under treatment with glucocorticoids. In general, the longer the duration of the disease and the more severe the subtype of the rheumatic disease, the shorter the height and the lower the bone density and bone strength parameters. Mean height, bone mineral content (BMC) and muscle cross-sectional area (CSA) were low for age, but muscle CSA was normal for height with the exception of patients with polyarticular disease. In the systemic JIA group the ratio of BMC per muscle CSA was decreased by -1.7+/-2.7 SD (P < 0.05), suggesting that bone strength was not adequately adapted to muscle force. This was even more expressed in females than in males (14 versus 3). These patients need closer follow up and potential specific therapeutic intervention.

Growth hormone improves height in patients with juvenile idiopathic arthritis: 4-year data of a controlled study.

OBJECTIVE: To evaluate the efficacy and safety of growth hormone treatment in severely growth retarded children with juvenile idiopathic arthritis (JIA) receiving glucocorticoids. STUDY DESIGN: Children with systemic and polyarticular idiopathic arthritis (22 F, 16 M) with a mean age of 10.1 years were enrolled in this controlled study. Eighteen patients (9 F, 9M; mean age, 10.5 years) received growth hormone in a dose of 0.20 to 0.33 mg/kg body weight per week for 4 years. Twenty patients (13 F, 7 M; mean age, 9.6 years) served as an untreated control group. RESULTS: Mean improvement in height in the treated group was 1 SD, whereas the patients of the control group lost 0.7 SD. Disease activity markers correlated significantly with the mean growth velocity standard deviation score. In general, children with mild or moderate disease and lower comedication grew and responded better to growth hormone therapy than those with active disease. No adverse events were noted. CONCLUSION: Our data suggest that long-term growth hormone therapy has a beneficial effect in children with severe forms of JIA. Further data are needed to confirm the efficacy and safety of growth hormone and its effect on final height.