Effects of short-term and long-term treatment with inhaled corticosteroids on bone metabolism in patients with airways obstruction. Dutch CNSLD Study Group.

Abstract

Background -Recent reports have suggested short term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain. Methods -Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 tg inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/ creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 jg beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2 5 years of treatment. Results -In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids. Conclusions -No detrimental long term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short term studies with single serum parameters of bone metabolism, but well designed long term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism. (Thorax 1994;49:652-656) Inhaled corticosteroids are currently administered to more patients with asthma and chronic obstructive pulmonary disease (COPD), at an earlier stage, and in higher dosages than previously.'13 Long term use of inhaled steroids has been shown to reduce exacerbations and hospital stay and to delay further deterioration of lung function.3 As far as current knowledge goes, however, this requires patients to take inhaled corticosteroids 2-4 times daily for many years. Although the short term direct adverse effects of inhaled corticosteroids seem to be acceptable, there is increasing discussion of possible adverse effects after years of usage.One of the important adverse effects of oral corticosteroids is osteoporosis, eventually leading to fractures.4 A few studies on the effects of inhaled corticosteroids on bone tu...

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

“…La observación de que la osteocalcina, sintetizada en el osteoblasto puede estimular la actividad del osteoclasto e inducir en parte la resorción y el recambio óseo, 25,26 sugiere ésta que no puede considerarse sólo como un marcador de formación sino también de resorción ósea. En mujeres posmenopáusicas, con riesgo aumentado de fractura de cadera, se observan valores elevados de osteocalcina 27 y un alto grado de correlación con el ICTP, 10 que es un marcador de resorción ósea. En pacientes asmáticos tratados con esteroides inhalados se ha notificado una disminución de la formación ósea por la reducción del PICP.…”

“…En la literatura se han notificado niveles variables de ICTP en estos pacientes; algunos autores encuentran niveles disminuidos de ICTP en los niños asmáticos tratados con esteroides inhalados, 23 mientras que otros, 10 no observaron aumento de ICTP.…”

“…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. Pacientes con asma severa que reciben esteroides inhalados a muy altas dosis y por tiempo prolongado podrían tener un riesgo de cierta pérdida ósea, pero esto es preferible a la alternativa de mantener un tratamiento con glucocorticoides orales para controlar la inflamación bronquial, con los que la pérdida ósea sería mucho mayor.…”

Effects of inhaled corticosteroids on bone

“…In this study in 8 healthy volunteers, a small decrease in AP was found after treatment with BDP 2.0 mg/day for 4 weeks, whereas after BUD 1.8 mg/day (n -8) no changes were observed. The significance of this open and small study is further more limited because of inaccurate statistical analy sis, Kerstjens et al [33] found no differences in AP after 4 weeks treatment with at least 0.8 mg of BDP or BUD.…”

“…Altogether, these findings indicate that in general ICS do not increase bone resorption. The long-term effects of ICS on bone metabolism are unclear, Kerstjens and colleagues [33] reported that long-term treatment with ICS did not affect biochemical markers of bone metabolism. PI CP and 1CTP remained unchanged after 2.5 years of treat ment with 0.8 mg BDP daily.…”