Compromised peak bone mass in patients with inflammatory bowel disease--a prospective study.

OBJECTIVE: To evaluate peak bone mass attainment in children and adolescents with inflammatory bowel disease and to identify risk factors for suboptimal bone mass attainment. STUDY DESIGN: We conducted a prospective follow-up study of 47 children and adolescents (24 males) with ulcerative colitis (n = 30) or Crohn's disease (n = 17). They were assessed for lumbar spine areal bone mineral density (aBMD) and for height-adjusted whole body less head bone mineral content (BMC); the values were corrected for bone age. RESULTS: Altogether, 73% of the patients had completed pubertal development after the median follow-up time of over 5 years. Despite clinical inactivity of the disease in 70% of the patients at the follow-up visit, BMD or BMC Z-scores improved in none of the measurement sites. Lumbar spine aBMD Z-scores (mean difference [95% CI], -0.47 [-0.92 to -0.03]; P = .04) and whole body less head BMC height- and bone age-adjusted Z-scores (-0.52 [-1.01 to -0.02]; P = .04) decreased in patients who were pubertal at baseline and completed their pubertal development during the follow-up. Postpubertal patients had lower aBMD and BMC Z-scores in comparison with prepubertal and pubertal patients. Low lumbar spine aBMD (Z-score < -1.0) was associated with completed pubertal development, underweight, and greater lifetime cumulative weight-adjusted prednisolone dose. Vertebral fractures were detected in 3 patients (6%). One-fourth of the patients had insufficient serum 25-hydroxyvitamin D concentrations (<50 nmol/L). CONCLUSIONS: The longitudinal follow-up over the pubertal years shows that inflammatory bowel disease poses a significant threat for bone health. The suboptimal peak bone mass attainment may have life-long consequences.

Impaired bone health in inflammatory bowel disease: a case-control study in 80 pediatric patients.

Previous studies have indicated that children with inflammatory bowel disease (IBD) may not achieve optimal bone mass. We evaluated the skeletal characteristics in children and adolescents with IBD. This cross-sectional cohort study comprised 80 IBD patients (median age 14.9 years, range 5-20) with a median disease duration of 3.4 years; 51 had ulcerative colitis, 26 Crohn disease, and 3 unspecified colitis. Eighty age- and gender-matched healthy subjects served as controls. Areal bone mineral density (aBMD), body composition, and vertebral fractures (VFs) were assessed by DXA. Bone age (BA) was determined for IBD patients. Findings were correlated with disease- and treatment-related parameters and biochemistry. IBD patients had lower BA-adjusted lumbar spine and whole-body aBMD (p < 0.001 for both) and whole-body BMC adjusted for height (p = 0.02) than controls. Lean mass and fat mass Z scores did not differ between the groups, but IBD patients had lower whole-body BMC relative to muscle mass (p = 0.006). Despite vitamin D supplementation in 48 %, vitamin D deficiency was common. In IBD cumulative weight-adjusted prednisolone dose >150 mg/kg for the preceding 3 years increased the risk for low whole-body aBMD (OR = 5.5, 95 % CI 1.3-23.3, p = 0.02). VFs were found in 11 % of patients and in 3 % of controls (p = 0.02). IBD in childhood was associated with low aBMD and reduced bone mass accrual relative to muscle mass; the risk for subclinical VFs may be increased. These observations warrant careful follow-up and active preventive measures.

[Update on current care guidelines: appropriate treatment of medical problems associated with Down's syndrome]. / Downin oireyhtymään liittyvien lääketieteellisten ongelmien hyvä hoito.

The lifetime prognosis of people with Down's syndrome has improved. Development of the services that health care and society can offer to such people is ongoing. These guidelines are targeted at defining what is required to further increase the lifespan and quality-of-life of people with Down's syndrome.

Circulating glucocorticoid bioactivity during peroral glucocorticoid treatment in children and adolescents with inflammatory bowel disease.

GOALS: Our objective was to investigate the changes in circulating glucocorticoid bioactivity (GBA) at the onset of systemic glucocorticoid therapy in pediatric patients with inflammatory bowel disease. STUDY: Prednisolone (1 mg/kg/d) or budesonide (9 mg/d) was introduced as a single daily dose, and the patients (n=22) were subsequently followed up at 2 to 4 week intervals. The limit for a raised value of serum GBA was defined in pediatric patients (mean+2 SD; 118 nM cortisol equivalents; n=142). RESULTS: Two weeks of prednisolone brought about an increase in serum GBA from 84+/-14 to 336+/-38 nM cortisol equivalents (mean+/-SE; P<0.001). Young patients (<10 y) had similar GBA values to older patients, even though their prednisolone dose was higher (1.3 vs. 0.79 mg/kg; P<0.05). Patients treated with budesonide displayed a minor increase in GBA (151+/-20 vs. 267+/-21 nM cortisol equivalents after 4 wk of treatment; P<0.05; n=3), and when switched to prednisolone (n=2), their GBA level increased 3-fold. GBA levels did not predict the development of glucocorticoid-related side effects. CONCLUSIONS: Prednisolone doses used in the treatment of pediatric inflammatory bowel disease patients elicit a 4-fold increase in serum GBA that is significantly higher than the increase induced by budesonide. The GBA measurement is an additional tool for assessing steroid therapy at an individual level during systemic glucocorticoid treatment.

Gluten-free diet may alleviate depressive and behavioural symptoms in adolescents with coeliac disease: a prospective follow-up case-series study.

BACKGROUND: Coeliac disease in adolescents has been associated with an increased prevalence of depressive and disruptive behavioural disorders, particularly in the phase before diet treatment. We studied the possible effects of a gluten-free diet on psychiatric symptoms, on hormonal status (prolactin, thyroidal function) and on large neutral amino acid serum concentrations in adolescents with coeliac disease commencing a gluten-free diet. METHODS: Nine adolescents with celiac disease, aged 12 to 16 years, were assessed using the semi-structured K-SADS-Present and Lifetime Diagnostic interview and several symptom scales. Seven of them were followed at 1 to 2, 3, and 6 months on a gluten-free diet. RESULTS: Adolescent coeliac disease patients with depression had significantly lower pre-diet tryptophan/ competing amino-acid (CAA) ratios and free tryptophan concentrations, and significantly higher biopsy morning prolactin levels compared to those without depression. A significant decrease in psychiatric symptoms was found at 3 months on a gluten-free diet compared to patients' baseline condition, coinciding with significantly decreased coeliac disease activity and prolactin levels and with a significant increase in serum concentrations of CAAs. CONCLUSION: Although our results of the amino acid analysis and prolactin levels in adolescents are only preliminary, they give support to previous findings on patients with coeliac disease, suggesting that serotonergic dysfunction due to impaired availability of tryptophan may play a role in vulnerability to depressive and behavioural disorders also among adolescents with untreated coeliac disease.

Orofacial granulomatosis in children--a challenge for diagnosis and treatment.

The data on orofacial granulomatosis, OFG, in children are sparse. We describe here 8 pediatric patients presenting with OFG, 2 of these cases associating with Crohn's disease. Therapeutic agents included systemic immunosuppressants such as glucocorticoids, methotrexate, anti-TNF-alpha agent, dapsone, antibiotics (metronidazole), and local treatment with topical tacrolimus or intralesional injections of triamcinolone hexacetonide. The treatment response ranged from good to poor results. The number of young patients suffering from OFG is not currently known and there are no gold standards for treatment. Thus, prospective follow-up studies on these patients are needed to gain more experience of the therapeutic responses.

Bone turnover and metabolism in paediatric patients with inflammatory bowel disease treated with systemic glucocorticoids.

OBJECTIVE: We investigated circulating markers of bone turnover before and during systemic glucocorticoid treatment in paediatric patients with inflammatory bowel disease (IBD). METHODS: Twenty-two children (mean age, 12.3 years) with IBD necessitating peroral steroid therapy were studied, with special reference to bone formation and resorption markers amino-terminal type I collagen propeptide (PINP) and carboxyterminal telopeptide of type I collagen (ICTP) respectively. In addition, GH-related IGF-I and sex hormone-binding protein (SHBG) were measured. Bone markers were analyzed at the initiation of the glucocorticoid treatment, at 2 and 5 weeks thereafter and at 1 month following the withdrawal of the steroid. Control group comprised 22 IBD patients in remission. RESULTS: PINP and IGF-I were already lower before glucocorticoid treatment serum in children with active IBD as compared with control children with IBD in remission (median PINP 271 vs 535 microg/l, P<0.05; IGF-I 23 vs 29 nmol/l, P<0.05). After 2 weeks of glucocorticoid treatment serum PINP levels had declined further, from 271 to 163 microg/l (P<0.001), serum ICTP from 14.2 to 9.6 microg/l (P<0.001), and SHBG from 54 to 35 nmol/l (P<0.001) respectively. By contrast, serum IGF-I increased from 23 to 37 nmol/l (P<0.001). One month after the withdrawal of the glucocorticoid, all bone markers restored to levels similar to the controls. CONCLUSIONS: Bone formation in children with active IBD appears compromised and systemic glucocorticoid treatment further suppresses bone turnover. After the cessation of the glucocorticoid the bone markers show immediate improvement.

Undiagnosed silent coeliac disease: a risk for underachievement?

OBJECTIVE: Silent coeliac disease is reported in 1% of Caucasian populations, but there is a lack of knowledge of its natural course and the risk of complications. The need for population screening is debated. We sought for complications of untreated coeliac disease in a well-defined cohort of Finnish adults. MATERIAL AND METHODS: Subjects (n=2427, ages 24-39 years) attending the 21-year follow-up visit of the study "Cardiovascular Risk in Young Finns" completed an extensive questionnaire on their health, diet, social situation and family life, and were given a medical examination. Measurement of serum IgA-transglutaminase and IgA-endomysium antibodies identified 21 subjects with silent coeliac disease. RESULTS: The subjects with silent coeliac disease did not differ from the rest of the cohort in age, gender, stature, weight, medical diagnoses (autoimmune, malignant), health concerns, use of alternative medications, physical activity, or in the cause of death their parents. They had lower serum HDL-cholesterol (1.12 versus 1.29 mmol/L; p=0.015), as described for active coeliac disease. Fewer (5.3% versus 22.8%; p=0.047) had a university or college degree or worked in managerial or professional positions (28% versus 45%; p=0.112). CONCLUSIONS: The underachievement in education and working life observed in subjects with silent coeliac disease is a new and intriguing finding and may be related to the increased prevalence of depressive and disruptive behavioural disorders described in teenagers with untreated coeliac disease. Our findings add a new ingredient to the ongoing discussion regarding the need for population screening for silent coeliac disease.

Helicobacter pylori serology at diagnosis and follow-up of biopsy-verified infection in children.

Data on the use of Helicobacter pylori serology in children are limited. We studied the serum antibodies of 105 H. pylori-infected children (median age 9.1 y, range 1.5-17.5 y) using an in-house enzyme immunoassay. At diagnosis of the biopsy-verified infection, IgG antibodies to H. pylori were elevated in 98/105 children (93%) but were at a normal level in 7 children, 5 of whom were < 5 y of age. Serum IgA antibodies to H. pylori were elevated in 40/105 children (38%). The levels of IgG and IgA antibody titers to H. pylori correlated with age (p < 0.001 and p < 0.02, respectively). IgG titers were reduced by > or = 50% in 85% (83/98; median follow-up 0.6 y) of children after therapy. In 56 such children eradication was verified by negative histology or urea breath test but I such child showed Helicobacters on histologic examination. Of the 15 children whose IgG titers dropped by < 50%, 7 were considered positive and 4 negative on the basis of histology or urea breath test. In 3 children, IgG titers returned to pretreatment levels 1 y after a 50% drop was seen. Serology is 1 alternative for monitoring H. pylori infection in children, although its sensitivity is lower in very young children. The length of follow-up needed after eradication, however, is unclear.

Mental disorders in adolescents with celiac disease.

A high prevalence of depressive symptoms, hypothetically related to serotonergic dysfunction, has been reported among adults with celiac disease. The authors used semistructured psychiatric interviews and symptom measurement scales to study mental disorders in 29 adolescents with celiac disease and 29 matched comparison subjects. Relative to the comparison subjects, the celiac disease patients had significantly higher lifetime prevalences of major depressive disorder (31% versus 7%) and disruptive behavior disorders (28% versus 3%). In most cases these disorders preceded the diagnosis of celiac disease and its treatment with a gluten-free diet. The prevalence of current mental disorders was similar in both groups. Celiac disease in adolescents is associated with an increased prevalence of depressive and disruptive behavioral disorders, particularly in the phase before diet treatment.