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Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review

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Abstract

Deleterious effect of oral corticosteroids on bone has been well documented, whereas this remains debated for inhaled ones (ICS). Our objectives were to analyze the effects of ICS on bone mineral density, fracture risk and bone markers. We performed an exhaustive systematic research of all controlled trials potentially containing pertinent data, peer-reviewed by a dedicated WHO expert group, and comprehensive meta-analyses of the data. Inclusion criteria were ICS, and BMD/markers/fractures in asthma/chronic obstructive pulmonary diseases (COPD) and healthy patients. Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, study design and ICS type. Results were expressed as standardized mean difference/effect size (ES), relative risk (RR) or odds ratio (OR), depending on study design and outcome units. Publication bias was investigated. Twenty-three trials were reviewed; 11 papers fit the inclusion criteria and were assessed for the main analysis. Quality scores for the randomized controlled trials (RCTs) were 80%, 71% for the prospective cohort studies, and 78% for the retrospective cohort and cross-sectional studies. We globally assessed ICS effects on BMD and found deleterious effects: ES=0.61 (p=0.001) for healthy subjects, and ES=0.27 (p<0.001) for asthma/COPD patients. For these patients, this effect was 0.21 (p<0.01) at the lumbar spine, and 0.26 (p<0.001) at the hip or femoral neck. A single study evaluated the impact of ICS on hip fracture and reported an increased OR of 1.6 (1.24; 2.03). Lumbar fracture rate differences did not reach the level of statistical significance: 1.87 (0.5; 6.94). Osteocalcin and PICP were decreased and ICTP, pyridinoline and deoxypyridinoline levels were not significantly affected. Budesonide (BUD) appeared to be the ICS inducing the less deleterious effects on bone, followed by beclomethasone dipropionate (BDP) and triamcinolone (TRI). Publication bias investigation provided non-significant results. In our meta-analyses, BUD at a mean daily dose (SD) of 686 μg (158 μg), BDP at 703 μg (123 μg) and TRI at 1000 μg (282 μg) were found to affect bone mineral density and markers in patients suffering from the two major respiratory diseases. These findings could have practical implication in the long-term management of asthmatic and COPD patients.

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Acknowledgement

The authors participated in this study on behalf of the WHO Collaborating Center for Public Health Aspects of Osteoarticular Disorders, Liège, Belgium.

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Author notes

  1. Florent Richy

    Present address: Santé Publique et Epidémiologie, Bâtiment B23, CHU Sart-Tilman, 4000 , Liège, Belgium

Authors and Affiliations

  1. WHO Collaborating Center for Public Health Aspects of Osteoarticular Disorders, Liège, Belgium

    Florent Richy, Olivier Bruyere & Jean-Yves Reginster

  2. Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Montpellier, France

    Jean Bousquet

  3. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

    George E. Ehrlich

  4. Service de de Rheumatologie, Pavillion F, Hôpital Edouard Herriot, Lyon, France

    Pierre J. Meunier

  5. Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Elliot Israel

  6. Osaka City University Medical School, Abeno-ku, Osaka, Japan

    Hirotoshi Morii

  7. Service de Rhumatologie, Cliniques Universitaires St. Luc, Brussels, Belgium

    Jean-Pierre Devogelaer

  8. Osteoporosis Centre, Northern General Hospital, Sheffield, UK

    Nicola Peel

  9. MSD-Chibret, France

    Muriel Haim

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  1. Florent Richy
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Correspondence to Florent Richy.

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Richy, F., Bousquet, J., Ehrlich, G.E. et al. Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review. Osteoporos Int 14, 179–190 (2003). https://doi.org/10.1007/s00198-003-1398-z

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  • DOI: https://doi.org/10.1007/s00198-003-1398-z

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