Effects of Recombinant Human Growth Hormone in Children with Crohn's Disease on the Muscle-Bone Unit: A Preliminary Study.

BACKGROUND/AIMS: There is limited information on the impact of recombinant human growth hormone (rhGH) on the muscle-bone unit in children with Crohn's disease (CD). In this pilot study, we report on the effects of rhGH on bone formation, dual-energy X-ray absorptiometry (DXA) total body (TB) bone mineral density adjusted for height and lumbar spine (LS) bone mineral apparent density (BMAD), and body composition. METHODS: Prospective study of 8 children with CD (6 male), aged 14.8 years (9.0-16.4), who received rhGH for 24 months. Serum procollagen type 1 N-terminal propeptide (P1NP) was measured at baseline and at 6 months. DXA was performed every 6 months. RESULTS: Six months of rhGH led to improvement in P1NP SDS adjusted for bone age from -3.6 (-7.9 to -0.9) to -2.4 (-3.7 to 0.4) (p = 0.01). At baseline, reduction in LS-BMAD and TB lean mass SDS was observed being -1.2 (-3.6 to 0.8) (p = 0.01 vs. zero) and -0.8 (-2.4 to 3.0) (p = 0.11 vs. zero), respectively. No significant changes were seen in DXA bone and muscle parameters over the 24 months. CONCLUSION: Twenty-four months of therapy with rhGH in CD did not lead to an improvement in DXA BMD and lean mass, despite improvement in P1NP and linear growth.

Disease Status and Pubertal Stage Predict Improved Growth in Antitumor Necrosis Factor Therapy for Pediatric Inflammatory Bowel Disease.

BACKGROUND: Growth failure is well-recognized in pediatric inflammatory bowel disease (PIBD; <18 years). We aimed to examine whether antitumor necrosis factor (TNF) therapy improves growth in a PIBD population-based cohort. METHODS: A retrospective review of all Scottish children receiving anti-TNF (infliximab [IFX] and adalimumab [ADA]) from 2000 to 2012 was performed; height was collected at 12 months before anti-TNF (T-12), start (T0), and 12 (T+12) months after anti-TNF. RESULTS: Ninety-three of 201 treated with IFX and 28 of 49 with ADA had satisfactory growth data; 66 had full pubertal data. Univariate analysis demonstrated early pubertal stages (Tanner 1-3 n = 44 vs T4-5 n = 22), disease remission, disease duration ≥2 years, and duration of IFX ≥12 months were associated with improved linear growth for IFX; for ADA only improvement was seen in Tanner 1-3. For IFX, Tanner 1-3 median Δ standard deviation scores for height (Ht SDS) -0.3 (-0.7, 0.2) at T0 changed to 0.04 (-0.5, 0.7) at T+12 (P < 0.001) versus -0.01 (-0.5, 0.9) at T0 in T4-5 changed to -0.01 (-0.4, 0.2) at T+12 (P > 0.05). For IFX disease duration ≥2 year, median Δ Ht SDS was -0.13 (-0.6, 0.3) at T0 then 0.07 (-0.3, 0.6) at T+12 (P < 0.001). Remission improved Δ Ht SDS (median Δ Ht SDS -0.14 [-0.6, 0.3] at T0 to 0.17 [-0.2, 0.7] at T+12 [P < 0.001]). Multiple regression analysis demonstrated corticosteroid usage at T0 predicted improved Δ Ht SDS at T+12 for IFX and ADA. CONCLUSIONS: Anti-TNF therapy is more likely to be associated with growth improvement when used at earlier stages of puberty with remission a key growth-promoting strategy in pediatric Crohn disease.

Assessing the feasibility of injectable growth-promoting therapy in Crohn's disease.

BACKGROUND: Despite optimal therapy, many children with Crohn's disease (CD) experience growth retardation. The objectives of the study are to assess the feasibility of a randomised control trial (RCT) of injectable forms of growth-promoting therapy and to survey the attitudes of children with CD and their parents to it. METHODS: A feasibility study was carried out to determine study arms, sample size and numbers of eligible patients. A face-to-face questionnaire surveyed willingness to consent to future participation in the RCT. Eligibility to the survey was any child under 18 (with their parent/guardian) with CD whose height standard deviation score (HtSDS) was ≤+1. Of 118 questionnaires, 94 (80%) were returned (48 by children and 46 by parents). RESULTS: The median age of the patients in the survey was 14.3 years (range 7.0 to 17.7), and 35 (73%) were male. Their median HtSDS was -1.2 (-3.01, 0.23), and it was lower than the median mid-parental HtSDS of -0.6 (-3.1, 1.4). We analysed the willingness of the children whose HtSDS <-1 to take part in the proposed RCT, being those most likely to require treatment. Overall, 18 (47%) children and 17 (46%) parents were willing. This increased to 61% of children who were slightly concerned about their height and 100% (4/4) of those very concerned. A common reason for not taking part in the RCT was fear of injections (44%); 111 children are required for randomisation into three study arms from nine centres. CONCLUSIONS: Almost half of children and parents surveyed would take part in an RCT of growth-promoting therapy. Allaying fears about injections may result in higher recruitment rates.

Endocrine therapy for growth retardation in paediatric inflammatory bowel disease.

Inflammatory bowel disease, particularly Crohn's disease (CD), can potentially cause growth failure during childhood as well as a reduction in final adult height. The underlying mechanism is multifactorial and includes poor nutrition, chronic inflammation, and the prolonged use of steroids. Despite major advances in the treatment of CD, current cohorts of children continue to display a deficit in linear growth and may qualify for growth-promoting hormonal therapy. However, currently there is limited evidence to support the use of endocrine therapy directed primarily at improving growth. This review is aimed at summarising the current evidence for growth impairment in inflammatory bowel disease and discusses the rationale for using growth promoting therapy.