Bone Mineral Density in Children Treated With Daily or Periodical Inhaled Budesonide: The Helsinki Early Intervention Childhood Asthma Study

Abstract

ABSTRACT:In a double-blind, randomized study, 136 children, 5-10-y-old, with newly detected persistent asthma received budesonide (BUD) 400 g twice daily for 1 mo and thereafter 200 g twice daily for 5 mo. Thereafter, 50 children were treated with BUD 100 g twice daily, whereas 44 children used BUD as needed for 1 y; an additional 42 children received disodium cromoglycate (DSCG). Asthma exacerbations were treated with BUD for 2 wk in a dose of 400 g twice daily in all groups. In this secondary analysis, bone mineral density (BMD) of the lumbar vertebrae was measured before and after the 18-mo treatment. Compared with DSCG, regular BUD treatment resulted in a significantly smaller increase in BMD (0.023 versus 0.034 g/cm 2 ; p ϭ 0.023) and height (7.75 versus 8.80 cm; p ϭ 0.001). Periodic treatment did not affect BMD. No intergroup differences were observed when BMD data were adjusted for changes in height. Daily BUD treatment in prepubertal children may slow down the increment in BMD and standing height. This was not observed in children receiving BUD periodically after the initial regular BUD treatment. The correlation between height and BMD suggests that following children's height might afford an estimation of inhaled corticosteroid effects on bone. (Pediatr Res 68: 169-173, 2010) I nhaled corticosteroids (ICS) are recommended first-line treatment for all patients with persistent asthma (1). Systemic exposure to corticosteroids can suppress bone formation and increase bone resorption resulting in loss of bone mass and risk of fractures (2). Also, in children, the use of oral steroids has been associated with a dose-dependent increase in fracture risk (3). Case-control studies, too, have identified an increased risk of fractures with high doses of ICS (4,5), particularly in elderly patients (6). Therefore, there has been some concern that the use of ICS as long-term asthma maintenance therapy in children could have a detrimental effect on bone mineral density (BMD) and risk of fractures.A recent Cochrane systematic review found that low to moderate doses of ICS did not affect BMD or risk of fractures in adults (7). However, it is not possible to extrapolate findings from adults to children. Bone mass in children is also influenced by height, age, race, exercise, presence of chronic illnesses, and especially the stage of puberty (8).The clinically most important outcome for the effects of ICS on bone is an increased risk of fractures. This is not easy to study, particularly, in children in randomized prospective trials. The use of biochemical markers is restricted to describe bone metabolism, but BMD has been used as a surrogate marker of an increased susceptibility to fractures. In this respect, BMD has some power to predict fractures (9). Therefore, prospective, randomized, long-term (Ͼ12 mo) controlled trials using clinically relevant doses of ICS with adjustment for confounders and with BMD as an endpoint seem to be the best way to assess the risk of clinically important adverse effects of ICS on the bone ...

An update on paediatric asthma

“…This study suggests that rescue therapy with ICS during tapering may be a beneficial strategy, and adds to the evidence that ICS at the time of viral infections may be beneficial in children with asthma. This study agrees with the Finnish data which suggests that intermittent ICS may be as effective, and with fewer side-effects, than continuous ICS in children with mild asthma [134][135][136].…”

Inhaled corticosteroids and bone mineral density at school age: A follow‐up study after early childhood wheezing

“…Due to the long follow‐up time, the median cumulative ICS dose in the present study was higher than in two previous French and Finnish studies . In the CAMP study, Danish study and recent Turkish study the ICS dose was higher than the median dose of this study .…”

Endocrine Effects of Inhaled Corticosteroids in Children

“…39 The threshold dose of ICSs for bone mineral loss has not been conclusively defined. Most pediatric studies [55][56][57][58] evaluated the effects of ICSs on lumbar spine BMD by dual-energy X-ray absorptiometry. A 2003 meta-analysis 59 of 6 studies of adults included a total of 635 asthmatic patients using 4 different ICSs for at least 3 years.…”