Effect of inhaled corticosteroids on bones and growth

Abstract

Asthma is a chronic inflammatory disease of the airways and current national and international asthma management guidelines advocate the early introduction of inhaled corticosteroids as the most effective anti-inflammatory therapy available [1][2][3][4]. However, inhaled corticosteroids are not entirely devoid of risk and their use in clinical practice entails a judgement that weighs the potential benefits against the risks of treatment [5][6]. The potential for systemic effects of inhaled corticosteroids is considered to be reflected in their activity of suppressing the hypothalamic-pituitary-adrenal (HPA) axis [7]. However, the clinical relevance of such suppression has been questioned [8] and concerns have been raised concerning the possible effects of inhaled corticosteroids on bones [9] and growth [10]. This review examines the effects of inhaled corticosteroids on bone metabolism, bone density and growth in adults and children with asthma, in view of the recent availability of a substantial amount of new information from clinical trials. Effect of corticosteroids on bone metabolismCorticosteroids may lead to a reduction in bone mass and osteopenia via several different mechanisms, including direct effects on bone formation and bone resorption and indirect effects via actions on the pituitary-gonadal and pituitary-adrenal axes, intestinal calcium absorption, renal tubular calcium reabsorption and secondary hyperparathyroidism ( fig. 1) [11]. A number of biochemical markers have been used to assess the short-term effects of inhaled corticosteroids on bone turnover [12] (table 1). Bone formation has been evaluated by measuring blood concentrations of bone-specific alkaline phosphatase, osteocalcin and procollagen type-1 carboxy-terminal and amino-terminal propeptides (P1CP and P1NP, respectively). Bone resorption has been evaluated by measuring urinary excretion of hydroxyproline, calcium and pyridinium cross-links and by serum levels of type-1 carboxy-terminal telopeptide (1CTP) and tartrate-resistant acid phosphatase. Examination of relevant retrospective and prospective data, involving 11 studies (1,240 patients) on biochemical bone markers and 14 studies (373 patients) on bone density over a wide dose range, have largely indicated no significant or clinically important effect on these measurements in adults or children with asthma. Markers of bone formation and resorption need to be measured concurrently for a reliable assessment of bone turnover to be made.Knemometry, measuring lower leg growth rate, is a sensitive technique for comparing the systemic activity of different inhaled corticosteroids, but does not relate to long-term growth. The majority of approximately 40 studies on inhaled corticosteroids and statural growth in children, over a wide recommended dose range, including a number of recent long-term, prospective studies, demonstrate little or no effect. Children taking above recommended doses of inhaled corticosteroids should have their growth monitored using stadiometry at least every 6 month...

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

“…The significance of such changes is unclear since there was no significant change in BMD [9,11,12,23]. In a study by TATTERSFIELD et al [24], osteocalcin concentrations increased slightly in the budesonide and reference therapy groups but remained unchanged in the BDP group, whereas concentrations of deoxypyrodinoline and pyrodinoline cross-links (markers of bone turnover) decreased slightly in the budesonide and reference therapy groups but remained unchanged in the BDP group.…”

Efecto de budesonida sobre la densidad y el metabolismo óseo en niños asmáticos

“…29,30 En los pacientes estudiados y tratados con budesonida inhalado no observamos cambios significativos en la densidad mineral ósea ni en el contenido mineral óseo. Este hallazgo, similar a lo informado por otros autores, 13,[31][32][33] es relevante, ya que el efecto de los esteroides inhalados sobre el hueso debe ser evaluado a largo plazo y con medidas específicas del estado óseo, como la den-sitometría ósea o el número de fracturas, más que con variaciones a corto plazo en los marcadores óseos. 10,23 El estudio de Martinati y colaboradores 31 incluyó la determinación de DMO cortical y trabecular (vertebral), al considerar que la mayor susceptibilidad a la pér-dida ósea inducida por los glucocorticoides podría resultar más ostensible en aquellas áreas donde predominara el tipo de hueso trabecular; sin embargo, no hubo diferencias al respecto.…”

Side-effects of high-dose fluticasone propionate in children

“…To the Editor: EFTHIMIOU and BARNES [1], in their review "Effect of inhaled corticosteroids on bones and growth", referred to our paper "Growth and adrenal suppression in asthmatic children treated with high dose fluticasone propionate" [2] as "anecdotal reports of growth deceleration in asthmatic children treated with inappropriately high doses (i.e. 5±10 times the recommended dose) of inhaled corticosteroids".…”