Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids

Mt, Saha; Laippala, Pekka; Lenko, Hanna Liisa

doi:10.1111/j.1651-2227.1997.tb08854.x

Cited by 58 publications

(23 citation statements)

References 26 publications

(3 reference statements)

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“…The final height attained correlated significantly with the child9s height before budesonide treatment, which in turn was significantly correlated with lung function, reflecting the fact that severity of asthma may itself influence growth. Such findings suggest that long-term therapy with inhaled budesonide has no clinically relevant effects on bone metabolism or growth in children: the reductions in growth reported in some previous studies [27][28][29] appear to be confined to the first 1-2 yrs of treatment, and catch-up growth occurs thereafter. This conclusion is consistent with the results of the recent Childhood Asthma Management Research Programme [30], in which the mean increase in height was significantly reduced during the first year in children receiving budesonide, compared with placebo-treated children, but the difference had disappeared by the second year.…”

Section: Discussionmentioning

confidence: 67%

Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler(R)

Johnell

Pauwels²,

Löfdahl

et al. 2002

European Respiratory Journal

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There is a need for studying the effects of long-term inhaled corticosteroid therapy on bone mineral density (BMD) and vertebral fracture rates in patients with mild chronic obstructive pulmonary disease (COPD).Patients (n=912, mean age 52 yrs) with mild COPD (mean forced expiratory volume in one second (FEV1) 77% of predicted; mean FEV1/slow vital capacity ratio 62%) were randomized to receive budesonide 400 mg, or placebo twice daily via Turbuhaler1. BMD was measured at the L2-L4 vertebrae and the femoral neck, trochanter and Ward9s triangle by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24 and 36 months (n=161). Radiographs of the thoracic and lumbar spine were obtained at the beginning and end of treatment (n=653).Previous fractures were present at baseline in 43 budesonide-treated patients (13.4%) and 38 placebo-treated patients (11.5%). New fractures occurred in five budesonidetreated patients, compared with three in the placebo group (p=0.50). There were no significant changes in BMD at any site in budesonide-treated patients, compared with the placebo group, during the course of the study. Budesonide treatment was associated with a slight but statistically significant decrease in the area under the concentrationtime curve for serum osteocalcin.In the present study, involving a large group of patients with chronic obstructive pulmonary disease, long-term treatment with budesonide 800 mg?day -1 via Turbuhaler1 had no clinically significant effects on bone mineral density or fracture rates.

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Section: Discussionmentioning

confidence: 67%

Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler(R)

Johnell

Pauwels²,

Löfdahl

et al. 2002

European Respiratory Journal

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“…Furthermore, clinicians must be alert for the possibility of drug-induced growth suppression so as not to misattribute it to growth suppression related to other causes. [23][24][25][26] To minimize the risks of systemic corticosteroid exposure, including growth suppression, dose-reduction strategies (eg, allergen-avoidance measures, immunotherapy and concomitant treatment with antihistamines, or decongestants) should be considered. 27 In addition, many allergic rhinitis patients also receive corticosteroids via other routes for the treatment of concomitant disorders, such as asthma or atopic dermatitis.…”

Section: Discussionmentioning

confidence: 99%

Detection of Growth Suppression in Children During Treatment With Intranasal Beclomethasone Dipropionate

Rachelefsky²,

et al. 2000

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ABSTRACT. Objective. Intranasal beclomethasone dipropionate (BDP) has generally been considered to have no systemic activity at recommended doses, but the potential for long-term effects on growth has not previously been evaluated. This study was undertaken to assess the effects of 1 year of treatment with intranasal BDP on growth in children.Study Design. In this double-blind, randomized, parallel-group study, 100 prepubertal children 6 to 9 years old with perennial allergic rhinitis were treated with aqueous BDP 168 g twice daily (n ‫؍‬ 51) or placebo (n ‫؍‬ 49) for 1 year. Subjects' baseline heights were required to be between the 5th and 95th percentile, and skeletal age as determined by left wrist radiograph was required to be within 2 years of chronological age. Washout periods for medications known to affect growth, including other forms of corticosteroids, were established, and these medications were prohibited during the study. However, short courses of oral prednisolone lasting no more than 7 days, and short courses of dermatologic corticosteroids lasting no more than 10 days, were allowed. Height was measured with a stadiometer after 1, 2, 4, 6, 8, 10, and 12 months of treatment. The hypothalamic-pituitary-adrenocortical axis was assessed by measurements of 8 AM basal cortisol concentrations and response to .25 mg cosyntropin stimulation.The primary safety parameter was the rate of change in standing height. Statistical analyses were based on all randomized subjects who received at least 1 dose of medication (intent-to-treat principle). The rate of change in standing height was analyzed for all subjects who entered the study and for those completing the full 12 months of treatment (n ‫؍‬ 80). The rate of change in standing height over the 1-year study was calculated as the slope of a linear regression line fitted to each subject's height measurements over time. Because there was a statistically significant between-group difference in standing height at baseline, an analysis of covariance was performed for all analyses of standing height data.Results. Of the 100 subjects enrolled, 90 completed the study. The 2 treatment groups were generally comparable at baseline; however, at baseline, mean age and mean height were significantly greater in the BDP treatment group that the in placebo treatment group. In both analyses, overall growth rate was significantly slower in BDP-treated subjects than placebo-treated subjects. The mean change in standing height after 1 year was 5.0 cm in the BDP-treated subjects compared with 5.9 cm in the placebo-treated subjects. The difference in growth rates was evident as early as the 1-month treatment visit, suggesting that the effect on growth occurred initially.The growth-suppressive effect of BDP remained consistent across all age and gender subgroups, and among subjects with and without a previous history of corticosteroid use. Use of additional exogenous corticosteroids during the study was similar in both groups and did not affect the results.Because there was a basel...

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“…The physiologic decrease in bone marker concentrations reported during late puberty does not seem to explain the changes seen in our steroid treated children because the exclusion of the oldest children did not change our finding. Growth suppression is usually most evident during the first year of inhaled steroid therapy (5,39). Our previous (3) and present findings suggest that the changes in adrenocortical function and bone metabolism during the initiation phase of inhaled steroid therapy may predict growth suppression.…”

Section: Bone Metabolism and Inhaled Steroidsmentioning

confidence: 91%

Biochemical Markers of Bone Metabolism in Relation to Adrenocortical and Growth Suppression During the Initiation Phase of Inhaled Steroid Therapy

Kannisto

2002

Pediatric Research

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Growth suppression is usually most evident during the first year of inhaled steroid therapy. Steroid-induced changes in bone metabolism may contribute to this growth suppression. The aim of the present study was to evaluate the changes in biochemical markers of bone metabolism in relation to adrenal and growth suppression during the initiation phase of inhaled steroid therapy. Seventy-five school-aged children with new asthma were enrolled into budesonide (BUD, n ϭ 30), fluticasone propionate (FP, n ϭ 30) or cromone (CROM, n ϭ 15) treatment groups. BUD dose was 800 g/d during the first two months and 400 g/d thereafter. The respective FP doses were 500 and 200 g/d. Biochemical markers of bone metabolism were measured before treatment and after 2 and 4 mo of therapy. In the control (CROM) group, the mean concentrations of serum osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP) (formation markers) and type I collagen carboxyterminal telopeptide (ICTP) (degradation marker) tended to increase. In the BUD group, OC and PICP decreased during the 4 mo by a mean of 23% (p Ͻ 0.001) and 15% (p Ͻ 0.05), respectively, while ICTP did not change significantly. In the FP group, OC and ICTP decreased during the first 2 mo by a mean of 19% (p Ͻ 0.01) and 21% (p Ͻ 0.01), respectively, returning to the pretreatment level at 4 mo, while PICP tended to increase during the 4 mo (14%, p ϭ 0.12).In the steroid treated children whose height SD score decreased during the first 12 mo of therapy, both OC and PICP decreased during the first 4 mo by a mean of 20% (p Ͻ 0.01) and 21% (p Ͻ 0.001), respectively. In those children who had no growth suppression, the changes were not significant: Ϫ4% in OC and ϩ13% in PICP. Furthermore, in children who developed evidence of adrenocortical suppression (on the basis of a low-dose ACTH test), OC decreased more (23%, p Ͻ 0.01) than in those with normal adrenocortical function (10%, p ϭ 0.06). In conclusion, both inhaled BUD and FP caused dose-dependent effects on biochemical markers of bone metabolism. The children who developed growth or adrenocortical suppression were likely to have changes also in bone metabolism. Asthmatic children treated with inhaled steroids seem to attain normal adult height (1). Despite this, inhaled steroids may at least temporarily suppress adrenocortical function (2, 3), growth (4, 5), and bone metabolism (6, 7). Glucocorticoids affect calcium metabolism (8, 9), and they can reduce bone formation by impairing the function of osteoblasts (10). Therefore, long-term use of inhaled steroids can cause osteopenia, at least in adults (11,12). There is a difference in the doseresponse relation between efficacy and systemic adverse effects of inhaled steroids. A plateau in the efficacy is reached at relatively low doses (13), while a linear relation between the dose and the effects on the adrenocortical function and bone metabolism continues for much higher doses (14).OC, the most abundant noncollagenous protein in bone matrix, is produced mainly by osteoblas...

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Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids

Cited by 58 publications

References 26 publications

Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler(R)

Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler(R)

Detection of Growth Suppression in Children During Treatment With Intranasal Beclomethasone Dipropionate

Biochemical Markers of Bone Metabolism in Relation to Adrenocortical and Growth Suppression During the Initiation Phase of Inhaled Steroid Therapy

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