Effects of high-dose inhaled corticosteroids on bone metabolism in prepubertal children with asthma

Allen, Hugh D.; Thong, Ian G.; Clifton‐Bligh, P.; Holmes, Susan; Nery, Liza; Wilson, Karen Byth

doi:10.1002/(sici)1099-0496(200003)29:3<188::aid-ppul6>3.0.co;2-k

Cited by 75 publications

(37 citation statements)

References 24 publications

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“…Three studies [60][61][62] found no deleterious effects of standard doses of beclomethasone or fluticasone on BMD in children 12 years and younger. However, a study 63 daily) for a mean (SD) of 2.9 (1.6) years revealed that lumbar BMD was more than 1 SD below the mean in 35% of treated patients compared with controls (P = .001). However, when correcting for bone age, this value decreased to 16%, which was no longer statistically significant.…”

Section: Primary Recommendationsmentioning

confidence: 96%

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Endocrine Effects of Inhaled Corticosteroids in Children

et al. 2016

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Section: Primary Recommendationsmentioning

confidence: 96%

“…60 Several studies [60][61][62][63] have looked at younger children to minimize the confounder of puberty. Three studies [60][61][62] found no deleterious effects of standard doses of beclomethasone or fluticasone on BMD in children 12 years and younger.…”

Section: Primary Recommendationsmentioning

confidence: 99%

Endocrine Effects of Inhaled Corticosteroids in Children

et al. 2016

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“…Inhaled corticosteroid treatment may be associated with normal or reduced bone mass in children [3,4,5,6,7,8,9,10,11,12]. Suppression of bone turnover has been demonstrated only for some markers of formation and resorption in children receiving inhaled steroids [13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

Are inhaled corticosteroids associated with an increased risk of fracture in children?

et al. 2004

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Inhaled corticosteroids are widely used in the long-term management of asthma in children. Data on the relationship between inhaled corticosteroid therapy and osteoporotic fracture are inconsistent. We address this issue in a large population-based cohort of children aged 4-17 years in the UK (the General Practice Research Database). The incidence rates of fracture among children aged 4-17 years taking inhaled corticosteroids (n=97,387), taking bronchodilators only (n=70 984) and a reference group (n=345,758) were estimated. Each child with a non-vertebral fracture (n=23,984) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. Fracture incidence was increased in children using inhaled corticosteroids, as well as in those receiving bronchodilators alone. With an average daily beclomethasone dose of 200 lg or less, the crude fracture risk relative to nonusers was 1.10 [95% confidence interval (CI), 0.96-1.26]; with dosage of 201-400 lg, it was 1.23 (95% CI, 1.08-1.39); and with dosages over 400 lg, it was 1.36 (95% CI, 1.11-1.67). This excess risk disappeared after adjustment for indicators of asthma severity. The increased risk of fracture associated with use of inhaled corticosteroids is likely to be the result of the underlying illness, rather than being directly attributable to inhaled corticosteroid therapy.

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“…In their retrospective review of 212 patients, Hougardy et al (10) reported that the median daily dose was 10 mg prednisolone equivalent and the median duration of oral corticosteroid treatment was 50 wk, which is well above the dosage capable of eliciting bone loss. Moreover, at an average dose of 0.67 mg⅐m Ϫ2 ⅐day Ϫ1 of inhaled steroids, there is a reduction in the acquisition of bone mineral in prepubertal children that compromises their peak bone mass and predisposes them to osteoporosis and a higher fracture risk as an adult (2). Therefore, we also wanted to determine whether we could quantify by pQCT with this model negative effects of corticosteroids on juvenile bone.…”

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confidence: 99%

In vivo rat assay: bone remodeling and steroid effects on juvenile bone by pQCT quantification in 7 days

McHugh¹,

Vercesi²,

Egan³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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. In vivo rat assay: bone remodeling and steroid effects on juvenile bone by pQCT quantification in 7 days. Am J Physiol Endocrinol Metab 284: E70-E75, 2003. First published September 3, 2002 10.1152/ajpendo. 00102.2002.-Anesthetized Sprague-Dawley weanling rats were scanned for bone mineral density (BMD) values after 7 days of treatment to determine whether resorption/growth at the proximal tibia can be quantified by peripheral quantitative computed tomography scanning techniques. Because the weanling rat is in a rapid growth stage, all groups showed significant increases in change from baseline values of BMD. Bisphosphonate treatment produced significant dose-related changes in BMD with average increases of 195 and 241% (10 and 20 g/kg) vs. 86% in control rats. We further characterized this model to determine effects of steroids on growing bone. Graded doses of glucocorticoid (3.5, 7.0, 10.5, 14.0, 28.0, and 42.0 mg ⅐ kg Ϫ1 ⅐ wk Ϫ1 ) caused no significant differences in trabecular BMD in 7 days between control and treated rats. Significant decreases in growth (weights) and increases in cortical bone area were observed, indicating that this model may be useful in comparing effects of nonsteroid, anti-inflammatory alternatives on juvenile bone. Although the relevance of this model to adult disease remains to be elucidated, it also provides a tool for mechanistic evaluation of therapeutic modalities or efficacy assessment for dose selection for longerterm models.osteoporosis; bone mineral density; glucocorticoid; computed tomography; animal model ANIMAL MODELS that simulate osteoporosis, such as ovariectomized rodents (postmenopausal) and glucocorticoid-induced and senescence-related osteopenia, are typically conducted in aged animals over long periods of time. In the case of senescence-induced osteoporosis, decrements in bone density may not be observed for 3 to 6 mo. The cost of boarding and large amounts of drugs that are needed to sustain these chronic models are thus often prohibitive. Moreover, this protracted study time is rate limiting to evaluation and development of novel therapeutic agents.Normal bone growth involves both bone resorption and bone formation in a well-controlled balance. It is proposed that administration of an anti-resorptive agent to the 21-day-old growing rat may disrupt the normal equilibrium at this time of fast growth, leading to a significantly higher bone mass in treated rats compared with age-matched untreated rats. In early studies, Schenk and colleagues [Muhlbauer et al. (16) and Schenk et al. (21)] utilized this 21-day-old model to screen bisphosphonate candidates. These studies showed that 7-day treatment with bisphosphonates yielded bones that demonstrated large increases in metaphysial density as measured by histology. The purpose of our study was to determine whether increases or decreases in apparent bone density can be quantified by peripheral quantitative computed tomography (pQCT) at an early time period.The 21-day-old rat represents a juvenile model of bone growt...

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Effects of high-dose inhaled corticosteroids on bone metabolism in prepubertal children with asthma

Cited by 75 publications

References 24 publications

Endocrine Effects of Inhaled Corticosteroids in Children

Endocrine Effects of Inhaled Corticosteroids in Children

Are inhaled corticosteroids associated with an increased risk of fracture in children?

In vivo rat assay: bone remodeling and steroid effects on juvenile bone by pQCT quantification in 7 days

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