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. 2002;2002(1):CD003537.
doi: 10.1002/14651858.CD003537.

Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease

A Jones  1 , J K Fay, M Burr, M Stone, K Hood, G Roberts
Affiliations

Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease

A Jones et al. Cochrane Database Syst Rev. 2002.

Abstract

Background: Inhaled corticosteroids form the main therapy for asthma, but there is increasing concern about the potential systematic effects of long-term inhaled corticosteroids including their effect on bone metabolism and bone loss.

Objectives: To determine the effect of inhaled corticosteroids use on biochemical markers of bone turnover, bone mineral density and the development of fractures.

Search strategy: We searched the Cochrane Airways Group trials register, electronic reference databases, UK National Research Register, bibliographies of included studies, and contacted pharmaceutical companies.

Selection criteria: Randomised trials of the effect of inhaled steroid versus placebo on markers of bone function and metabolism, in adults with asthma or mild COPD.

Data collection and analysis: Trial quality was assessed and data extracted from the papers included (2 reviewers per paper) and from additional data supplied by the authors.

Main results: Of 438 references found, seven met the inclusion criteria. Three studies were in healthy subjects asthma or COPD. The patients were generally less than 60 years old and the male:female ratio was 2:1. There was no evidence of increased risk of loss of bone mineral density (BMD) or fractures. There was no significant change in osteocalcin at conventional doses of inhaled corticosteroids (Standardised Mean Difference [SMD] -0.34 (95% Confidence Interval [CI] -0.72, 0.04), although a statistically significant change was seen in those studies using experimental doses of inhaled steroid in excess of the doses recommended by the British Thoracic Society SMD 0.97 (95% CI -1.61, -0.34). A statistically significant change in parathyroid hormone seen in one small short trial (n=10, 6 weeks) may have been due to the trial design and outcome measurements used.

Reviewer's conclusions: In patients with asthma or mild COPD, there is no evidence of an effect of inhaled corticosteroid at conventional doses given for two or three years on BMD or vertebral fracture. Higher doses were associated with biochemical markers of increased bone turnover, but data on BMD and fractures at these doses are not available. There is a need for further, even longer term prospective studies of conventional and high doses of inhaled corticosteroids.

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Conflict of interest statement

None known.

Comment in

References

References to studies included in this review

EUROSCOP 1999 {published and unpublished data}
    1. Johnell O, Pauwels RA, Ohlsson SV, Ekelund J. Long‐term treatment with inhaled budesonide did not effect bone mineral density or bone markers in patients with chronic obstructive pulmonary disease. American Society for Bone and Mineral Research Meeting. 1999; Vol. Poster Presentation.
    1. Pauwels RA, Lofdahl C‐G, Laitinen LA, Schouten JP, Postma DS, Pride NB, et al. Long‐term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue to smoke. The New England Journal of Medicine 1999;340:1948‐53. - PubMed
Hodsman 1991 {published and unpublished data}
    1. Hodsman AB, Toogood JH, Jennings B, Fraher LJ, Baskerville JC. Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin. Journal of Clinical Endocrinology and Metabolism 1991;72:530‐40. - PubMed
Kerstjens 1994 {published and unpublished data}
    1. Kerstjens HAM, Postma DS, Doormaal JJ, Zanten AK, Brand PLP, Dekhuijzen PNR, et al. Effects of short term and long term treatment with inhaled corticosteroids on bone metabolism in patients with airways obstruction. Thorax 1994;49:652‐6. - PMC - PubMed
Leech 1993 {published data only}
    1. Leech JA, Hodder RV, Ooi DS, Gay J. Effects of short‐term inhaled budesonide and beclomethasone dipropionate on serum osteocalcin in premenopausal women. Americal Review of Respiratory Disease 1993;148:113‐5. - PubMed
Li 1999 {published data only}
    1. Li JTC, Ford LB, Chervinsky P, Weisberg SC, Kellerman DJ, Faulkner KG, et al. Fluticasone propionate powder and lack of clinically significant effects on hypothalmic‐pituitary‐adrenal axis and bone mineral density over 2 years in adults with mild asthma. Journal of Allergy Clinical Immunology 1999;103:1062‐8. - PubMed
Tattersfield 2001 {published data only}
    1. Tattersfield AE, Town GI, Johnell O, Picado C, Aubier M, Braillon P, et al. Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non‐corticosteroid treatment for two years. Thorax 2001;56:272‐8. - PMC - PubMed
Toogood 1991 {published and unpublished data}
    1. Toogood JH, Jennings B, Hodsman AB, Baskerville J, Fraher LJ. Effects of dose and dosing schedule of inhaled budesonide on bone turnover. Journal of Allergy and Clinical Immunology 1991;88:572‐80. - PubMed

References to studies excluded from this review

Barnes 1996 {unpublished data only}
    1. Barnes PJ, National Heart and Lung Institute. Assessment of long‐term efficacy of early introduction of inhaled steroids in asthma (ELSAT) a pilot study in general practice. NRR 1996.
Bootsma 1996 {published data only}
    1. Bootsma GP, Dekhuijzen PNR, Festen J, Mulder PGH, Swinkles LMJW, Herwaarden CLA. Fluticasone propionate does not influence bone metabolism in contrast to beclomethasone dipropionate. American Journal of Respiratory & Critical Care Medicine 1996;153:924‐30. - PubMed
Clark 1997 {published data only}
    1. Clark DJ, Lipworth BJ. Adrenal suppression with chronic dosing of fluticasone propionate compared with budesonide in adult asthmatic patients. Thorax 1997;52:55‐8. [osteo RM 37; asthma RM 1036] - PMC - PubMed
Dempsey 1999 {published data only}
    1. Dempsey OJ, Coutie WJR, Wilson AM, Williams P, Lipworth BJ. Evaluation of the buccal component of systematic absorption with inhaled fluticasone propionate. Thorax 1999;54:614‐7. - PMC - PubMed
Egan 1999 {published data only}
    1. Egan JJ, Maden C, Kalra S, Adams JE, Eastell R, Woodcock AA. A randomized, double‐blind study comparing the effects of beclomethasone and fluticasone on bone density over two years. European Respiratory Journal 1999;13(6):1267‐75. - PubMed
Gross 1999 {published data only}
    1. Gross G, Thompson PJ, Chervinsky P, Vanden Burgt J. Hydrofluoroalkane‐134a beclomethasone dipropionate, 400 microg, for the treatment of moderate asthma. Chest 1999;115(2):343‐51. - PubMed
Harmanci 1998 {published data only}
    1. Harmanco E, Colak O, Ozdemir N, Alatas O, Isik R. Fluticasone propionate and budesonide does not influence bone metabolism in the long term treatment of asthma [(abstract funded by Glaxo Welcome)]. European Respiratory Journal 1998;12(Suppl. 28).
Herrala 1994 {published data only}
    1. Herrala J, Puolijoki H, Impivaara O, Liippo K, Tala E, Nieminen MN. Bone mineral density in asthmatic women on high‐dose inhaled beclomethasone dipropionate. Bone 1994;15(6):621‐3. - PubMed
Hughes 1999 {published data only}
    1. Hughes JA, Conry BG, Male SM, Eastell R. One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate and budesonide on bone markers and bone mineral density. Thorax 1999;54:223‐9. - PMC - PubMed
Johnell 1999 {published data only}
    1. Johnell O, Aubier M, BrallionP, Karlstrom R, Picado C, Tattersfield AE, et al. Long‐term effects on bone markers by inhaled steroids compared with non‐steroid reference therapy. A randomised trial. American Society for Bone and Mineral Research Meeting 1999; Vol. Poster presentation.
Kos‐Kudla 1997 {published data only}
    1. Kos‐Kudla B, Pluskiewicz W. Quantitative ultrasound of the heel and serum and urinary cortisol values in assessment of long‐term corticotherapy side effects in female bronchial asthma patients. Ultrasound in Medicine and Biology 1997;23(9):1325‐30. [26] - PubMed
Malo 1999 {published data only}
    1. Malo J‐L, Cartier A, Ghezzo H, Mark S, Brown J, Laviolette M, Boulet L‐P. Skin bruising, adrenal function and markers of bone metabolism in asthmatics using inhaled beclomethasone and fluticasone. European Respiratory Journal 1999;13:993‐8. - PubMed
Nikolaizik 1996 {published data only}
    1. Nikolaizik WH, Marchant JL, Preece MA, Warner JO. Nocturnal cortisol secretion in healthy adults before and after inhalation of budesonide. American Journal of Respiratory and Critical Care Medicine 1996;153:97‐101. [33] - PubMed
Padfield 1993 {published data only}
    1. Padfield PL, Teelucksingh S. Inhaled steroids: the endocrinologist's view. European Respiratory Review 1993;3:494‐500. [43]
Paggiaro 1998 {published data only}
    1. Paggiaro PL, Dahle R, Bakran I, Frith L, Hollingworth K, Efthimiou J. Multicentre randomised placebo‐controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. Lancet 1998;351:773‐80. - PubMed
Pauwels 1998 {published data only}
    1. Pauwels RA, Yernault JC, Demedts MG, Geusens P, Belgian Multicenter Group. Safety and efficacy of fluticasone and beclomethasone in moderate to severe asthma. American Journal of Respiratory & Critical Care Medicine 1998;157:827‐832. - PubMed
Struijs 1997 {published data only}
    1. Struijs A, Mulder H. The effects of inhaled glucocorticosteroids on bone mass and biochemical markers of bone homeostasis: a 1‐year study of beclomethasone versus budesonide. The Netherlands Journal of Medicine 1997;50:233‐7. - PubMed
Suissa 2000 {published data only}
    1. Suissa S, Ernst P, Benaynon S, Baltzan M, Chai B. Low‐dose inhaled corticosteroids and the prevention of death from asthma. The New England Journal of Medicine 2000;343(5):332‐6. - PubMed
Toogood 1988 {published data only}
    1. Toogood JH, Crilly RG, Jones G, Nadeau J, Wells GA. Effect of high‐dose inhaled budesonide on calcium and phosphate metabolism and the risk of osteoporosis. American Review of Respiratory Disease 1988;138:57‐61. - PubMed
Vickers 1999 {published data only (unpublished sought but not used)}
    1. Vickers M, MRC Epidemiology and Medical Care Unit. An assessment of long‐term efficacy of early introduction of inhaled steroids in asthma. NRR 1999.
Wilson 1997 {published data only}
    1. Wilson AM, Clark DJ, McFarlane L, Lipworth BJ. Adrenal suppression with high doses of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers. European Journal of Clinical Pharmacology 1997;53:33‐7. [27] - PubMed
Wilson 1997b {published data only}
    1. Wilson AM, McFarlane LC, Lipworth BJ. Dose‐response effect for adrenal suppression with repeated twice daily inhaled fluticasone propionate and triamcinolone acetonide in adult asthmatics. Americal Journal of Respiratory and Critical Care Medicine 1997;156:1274‐7. [41] - PubMed
Wilson 1998 {published data only}
    1. Wilson AM, Brewester HJA, Lipworth BJ. Dose‐response comparison of systematic bioactivity with inhaled budesonide and triamcinolone acetonide in asthmatic adults. Journal of Allergy & Clinical Immunology 1998;102:751‐6. [Osteo Ref Man 28] - PubMed
Wilson 1998c {published data only}
    1. Wilson AM, McFarlane LC, Lipworth BJ. Systematic bioactivity profiles of oral prednisolone and nebulised budesonide in adult asthmatics. Chest 1998;114:1022‐7. - PubMed
Wilson 1999 {unpublished data only}
    1. Wilson AM, Lipworth BJ. 24 hour fractionated profiles of adrenocortical activity in asthmatic patients receiving inhaled and intranasal corticosteroids. Thorax 1999;54:20‐6. [42] - PMC - PubMed
Wilson1998b {published data only}
    1. Wilson AM, Clark DJ, Devlin MM, McFarlane LC, Lipworth BJ. Adrenocortical activity with repeated administration of one‐daily inhaled fluticasone propionate and budesonide in asthmatic adults. European Journal of Clinical Pharmacology 1998;53:317‐20. [29] - PubMed
Wood 1999 {published data only}
    1. Wood LJ, Sehmi R, Gauvreau GM, Watson RM, Foley R, Denburg JA, et al. Inhaled corticosteroid, budesonide, reduces baseline but not allergen‐induced increases in bone marrow inflammatory cell progenitors in asthmatic subjects. American Journal of Respiratory & Critical Care Medicine 1999;159:1457‐63. [38] - PubMed

References to studies awaiting assessment

Burge 2000 {published data only}
    1. Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 2000;320:1297‐303. - PMC - PubMed
Osur 1998 {published data only}
    1. Osur S, Chervinsky P, Herje N, Harding S, Kellerman D. Long term effects of fluticasone propionate inhalation aerosol in subjects with asthma [(Abstract funded by Glaxo Wellcome) (Requested 22 /9 /00 Morriston)]. American Journal of Respiratory & Critical Care Medicine 1998;157(3):A405.
Wise 2000 {published data only}
    1. Wise R, Connett J, Weinmann G, Scanlon P, Skeans M. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. New England Journal of Medicine 2000;343:1902‐9. - PubMed
Yernault 2000 {published data only}
    1. Yernault JC, Geusens P, Wilder P, Belgian Multi‐Center Group. Lack of negative effect of a daily dose of 500 ‐ 1000mcg inhaled fluticasone on bone mineral density in asthmatics. American Journal of Respiratory & Critical Care Medicine 2000;161(3):Abstract funded by Glaxo Welcome.

Additional references

Agertoft 1994
    1. Agertoft L, Pedersen S. Effects of long term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respiratory Medicine 1994;88:373‐81. [915] - PubMed
Anderson 1994
    1. Anderson HR, Butland BK, Strachan DP. Trends in prevalence and severity of childhood asthma. BMJ 1994;308:1600‐4. [685] - PMC - PubMed
BTS 1997
    1. British Thoracic Society. British Thoracic Society Asthma Guidelines. Thorax 1997;52(Supplement 1):S11.
Garnero 1998
    1. Garnero P, Delmas PD. Biochemical markers of bone turnover. Endocrinology & Metabolism Clinics of North America 1998;27(2):303‐23. - PubMed
Geddes 1992
    1. Geddes DM. Inhaled corticosteroids: benefits and risks. Thorax 1992;47:404‐7. [911] - PMC - PubMed
Hanania 1995
    1. Hanania NA, Chapman KR. Dose related decrease in bone density among asthmatic patients treated with inhaled corticosteroids. Journal of Allergy and Clnical Immunology 1995;96(5 part 1):571‐9. [1501] - PubMed
Luengo 1991
    1. Luengo M, Picardo C, Rio LD, Guanabens N, Monserrat JM, Setoain J. Vertebral fractures in steroid dependent asthma and involutional osteoporosis: a comparative study. Thorax 1991;46:803‐6. - PMC - PubMed
Miller 1999
    1. Miller PD, Baram DT, Bilezikian JP, et al. Practical clinical application of biochemical markers of bone turnover (consensus of an expert panel). Journal of Clinical Densitometry 1999;2:323‐42. - PubMed
Pauwels 1995
    1. Pauwels P. The current status of asthma guidelines. European Respiratory Review 1995;4(26):105‐7. [786]
Riggs 2000
    1. Riggs BL. Are biochemical markers for bone turnover clinically useful for monitoring therapy in individual osteoporotic patients?. Bone June 2000;26(6):551‐2. - PubMed
Swaminathan 1997
    1. Swaminathan R. Biochemical Markers for Osteoporosis. In: Arden NK, Spector TD editor(s). Osteoporosis Illustrated. A comprehensive illustrated guide to osteoporosis. London: Current Medical Literature Ltd, 1997:75.
Tattersfield 1997
    1. Tattersfield AE. Limitations of current treatment. Lancet 1997;350(Suppl. 11):24‐7. [1198] - PubMed
Teelucksingh 1991
    1. Teelucksingh S. Inhaled corticosteroids, bone formation and osteocalcin. Lancet 1991;338:60‐1. - PubMed
Toogood 1995
    1. Toogood JH, Baskerville JC, Markov AE, Hodsman AB, Frayer LJ, Jennings B, et al. Bone mineral density and the risk of fracture in patients receiving long‐term inhaled steroid therapy for asthma. Journal of Allergy and Clinical Immunology 1995;96(2):157‐66. - PubMed

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