Journal of Bone and Mineral Metabolism

, Volume 26, Issue 5, pp 485–492 | Cite as

Cross-sectional study on bone density-related sonographic parameters in children with asthma: correlation to therapy with inhaled corticosteroids and disease severity

  • Jochen G. Mainz
  • Dieter Sauner
  • Ansgar Malich
  • Stephanie John
  • Heike Beyermann
  • Hans-Joachim Mentzel
  • Werner A. Kaiser
  • Felix Zintl
Original Article


The aim of this study was to screen asthmatic children for bone density-related sonographic parameters on the calcaneal bone. Findings were correlated to therapy with inhaled corticosteroids (ICS) as well as with asthma severity (AS), concomitance and severity of atopic dermatitis (AD), and rhinitis (AR). We enrolled 173 children with AS1-3 consecutively; 44% (AS1) had not received any ICS medication; 56% (AS2 and −3) received ICS therapy for ≥6 months (medium daily dose, 286 μg fluticasone-proprionate-equivalent/maximum 500 μg); and in addition 38% (n = 65) presented with AD and 66% (n = 115) with AR. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) results were compared to regional normative values of 3299 children obtained with the identical system. ICS-treated children showed a tendency toward reduced age-, weight-, and height-adjusted standard deviation scores (SDS) for SOS compared to children without ICS treatment, which tendency did not reach statistical significance and was not as consistent for BUA (mean of ICS-treated children compared to our controls: SOS-SDS, −0.29/−0.31/−0.30; BUA-SDS, −0.23/−0.17/−0.05). For ICS-treated children, the proportion of patients with BUA and SOS values below −1 SDS was statistically significant higher for age-adjusted BUA and SOS than for children without ICS medication (BUA 15.00% vs. 5.41%; SOS 32.98% vs. 17.56%). However, we cannot differentiate possible negative effects of ICS from influences of the underlying inflammatory disease because higher asthma severity was associated with greater use of ICS medication. Additionally, the higher physical activity of children with less severe asthma can have influenced quantitative ultrasound (QUS) parameters positively, compared to patients with a higher degree of exercise-induced symptoms. For differentiation of possible negative effect of ICS on ultrasonic bone quality and for evaluation of the potentials of the method, further longitudinal QUS assessment of asthmatics receiving a new ICS treatment is needed.

Key words

asthma ultrasound osteoporosis bone density inhaled corticosteroids 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Illi S, von Mutius E, Lau S, Nickel R, Grüber C, Niggemann B, Wahn U; Multicenter Allergy Study Group (2004) Multicenter Allergy Study Group. The natural course of atopic dermatitis from birth to age of 7 years and the association with asthma. J Allergy Clin Immunol 113:925–931PubMedCrossRefGoogle Scholar
  2. 2.
    Chinn S, Jarvis D, Burney P, Luczynska C, Ackermann-Liebrich U, Antó JM, Cerveri I, De Marco R, Gislason T, Heinrich J, Janson C, Künzli N, Leynaert B, Neukirch F, Schouten J, Sunyer J, Svanes C, Vermeire P, Wjst M (2004) Increase in diagnosed asthma but not in symptoms in the European Community Respiratory Health Survey. Thorax 59:646–651PubMedCrossRefGoogle Scholar
  3. 3.
    Anderson HR, Ruggles R, Strachan DP, Austin JB, Burr M, Jeffs D, Standring P, Steriu A, Goulding R (2004) Trends in prevalence of symptoms of asthma, hay fever, and eczema in 12–14 year olds in the British Isles, 1995–2002: questionnaire survey. BMJ 328: 1052–1053PubMedCrossRefGoogle Scholar
  4. 4.
    Adinoff AD, Hollister JR (1983) Steroid-induced fractures and bone loss in patients with asthma. N Engl J Med 309:265–268PubMedGoogle Scholar
  5. 5.
    Ledford D, Apter A, Brenner AM, Rubin K, Prestwood K, Frieri M, Lukert B (1998) Osteoporosis in the corticosteroid-treated patient with asthma. J Allergy Clin Immunol 102:353–362PubMedCrossRefGoogle Scholar
  6. 6.
    Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2005) Use of oral corticosteroids and risk of features. J Bone Miner Res 20:1487–1494; discussion 1486PubMedCrossRefGoogle Scholar
  7. 7.
    Barnes PJ, Pedersen S (1993) Efficacy and safety of inhaled corticosteroids in asthma. Am Rev Respir Dis 148:1–26Google Scholar
  8. 8.
    Hatoum HT, Schumock GT, Kendzierski DL (1994) Meta-analysis of controlled trials of drug therapy in mild chronic asthma: the role of inhaled corticosteroids. Ann Pharmacother 28:1285–1289PubMedGoogle Scholar
  9. 9.
    O’Connell EJ (2005) Optimizing inhaled corticosteroid therapy in children with chronic asthma. Pediatr Pulmonol 39:74–83PubMedCrossRefGoogle Scholar
  10. 10.
    Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, Gibson P, Ohta K, O’Byrne P, Pedersen SE, Pizzichini E, Sullivan SD, Wenzel SE, Zar HJ (2008) Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 31:143–178PubMedCrossRefGoogle Scholar
  11. 11.
    Global Initiative for Asthma (1995) Global strategy for asthma management and prevention. Publication no. 95-3659. Heart, Lung and Blood Institute, Washington, DCGoogle Scholar
  12. 12.
    Hanania NA, Chapman KR, Sturtridge WC, Salai JP, Kesten S (1995) Dose-related decrease in bone density among asthmatic patients treated with inhaled corticosteroids. J Allergy Clin Immunol 96:571–579PubMedCrossRefGoogle Scholar
  13. 13.
    Woodcock A (1998) Effects of inhaled corticosteroids on bone density and metabolism. J Allergy Clin Immunol 101:456–459CrossRefGoogle Scholar
  14. 14.
    Griffiths AL, Sim D, Strauss B, Rodda C, Armstrong D, Freezer N (2004) Effect of high-dose fluticasone propionate on bone density and metabolism in children with asthma. Pediatr Pulmonol 37:116–121PubMedCrossRefGoogle Scholar
  15. 15.
    Medici TC, Grebski E, Häcki M, Rüegsegger P, Maden C, Efthimiou J (2000) Effect of one year treatment with inhaled fluticasone propionate or beclomethasone dipropionate on bone density and bone metabolism: a randomised parallel group study in adult asthmatic subjects. Thorax 55:375–382PubMedCrossRefGoogle Scholar
  16. 16.
    Agertoft L, Pederen S (1998) Bone mineral density in children with asthma receiving long term treatment with inhaled budesonide. Am J Respir Crit Care Med 157:178–183PubMedGoogle Scholar
  17. 17.
    Egan JJ, Maden C, Kalra S, Adams JE, Eastell R, Woodcock AA (1999) A randomized, double-blind study comparing the effects of beclomethasone and fluticasone on bone density over two years. Eur Respir J 13:1267–1275PubMedGoogle Scholar
  18. 18.
    Packe GE, Robb O, Robins SP, Reid DM, Douglas JG (1996) Bone density in asthmatic patients taking inhaled corticosteroids: comparison of budesonide and beclomethasone dipropionate. J R Coll Phys Lond 30:128–132Google Scholar
  19. 19.
    Ebeling PR, Erbas B, Hopper JL, Wark JD, Rubinfeld AR (1998) Bone mineral density and bone turnover in asthmatics treated with long-term inhaled or oral glucocorticoids. J Bone Miner Res 13: 1283–1289PubMedCrossRefGoogle Scholar
  20. 20.
    Hanania NA, Chapman KR, Kesten S (1995) Adverse effects of inhaled corticosteroids. Am J Med 98:196–208PubMedCrossRefGoogle Scholar
  21. 21.
    Allen HD, Thong IG, Clifton-Bligh P, Holmes S, Nery L, Wilson KB (2000) Effects of high-dose inhaled corticosteroids on bone metabolism in prepubertal children with asthma. Pediatr Pulmonol 29:188–193PubMedCrossRefGoogle Scholar
  22. 22.
    Hans D, Hartl F, Krieg MA (2003) Device-specific weighted T-score for two quantitative ultrasounds: operational propositions for the management of osteoporosis for 65 years and older women in Switzerland. Osteoporos Int 14:251–258PubMedGoogle Scholar
  23. 23.
    Malich A, Mainz J, John S, Vogt S, Beyermann H, Mentzel HJ, Wünsche K, Zintl F, Kaiser WA (2003) Early results of ultrasound based calculation of broadband ultrasound attenuation and speed of sound in children and adolescents suffering from asthma. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 175: 366–373PubMedCrossRefGoogle Scholar
  24. 24.
    van Lenthe GH, van den Bergh JP, Hermus AR, Huiskes R (2001) The prospects of estimating trabecular bone tissue properties from the combination of ultrasound, dual energy X-ray absorptiometry, microcomputed tomography, and microfinite element analysis. J Bone Miner Res 16:550–555PubMedCrossRefGoogle Scholar
  25. 25.
    Bauer DC, Glüer CC, Cauley JA, Vogt TM, Ensrud KE, Genant HK, Black DM (1997) Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. A prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med 157:629–634PubMedCrossRefGoogle Scholar
  26. 26.
    Hans D, Dargent-Molina P, Schott AM, Sebert JL, Cormier C, Kotzki PO, Delmas PD, Pouilles JM, Breart G, Meunier PJ (1996) Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet 348: 511–514PubMedCrossRefGoogle Scholar
  27. 27.
    Yung PS, Lai YM, Tung PY, Tsui HT, Wong CK, Hung VW, Qin L (2005) Effects of weight bearing and non-weight bearing exercises on bone properties using calcaneal quantitative ultrasound. Br J Sports Med 39(8):547–551PubMedCrossRefGoogle Scholar
  28. 28.
    Mentzel HJ, Wünsche K, Malich A, Böttcher J, Vogt S, Kaiser WA (2005) The effects of sports activities in children and adolescents on the calcaneus: an investigation with quantitative ultrasound. Rofo 177(4):524–529PubMedGoogle Scholar
  29. 29.
    Schalamon J, Singer G, Schwantzer G, Nietosvaara Y (2004) Quantitative ultrasound assessment in children with fractures. J Bone Miner Res 19(8):1276–1279PubMedCrossRefGoogle Scholar
  30. 30.
    Drozdzowska B (2005) Skeletal status assessed by quantitative ultrasound at the calcaneus in females with bronchial asthma on prolonged corticosteroid therapy. Maturitas 51(4):386–392PubMedCrossRefGoogle Scholar
  31. 31.
    Wünsche K, Wünsche B, Fähnrich H, Mentzel HJ, Vogt S, Abendroth K, Kaiser WA (2000) Ultrasound bone densitometry of the os calcis in children and adolescents. Calcif Tissue Int 67:349–355PubMedCrossRefGoogle Scholar
  32. 32.
    American Thoracic Society (1962) Definition and classification of chronic bronchitis, asthma, and pulmonary emphysema. Am Rev Respir Dis 85:762–768Google Scholar
  33. 33.
    Colice GL, Burgt JV, Song J, Stampone P, Thompson PJ (1999) Categorizing asthma severity Am J Respir Crit Care Med 160: 1962–1967PubMedGoogle Scholar
  34. 34.
    Wettengel R, Berdel D, Hofmann D, Krause J, Kroegel C, Kroidl RF, Leupold W, Lindemann H, Magnussen H, Meister R, Morr H, Nolte D, Rabe K, Reinhardt D, Sauer R, Schultze-Werninghaus G, Ukena D, Worth H (1998) Asthmatherapie bei Kindern und Erwachsenen. Med Klin 93:639–650Google Scholar
  35. 35.
    Consensus Report of the European Task Force on Atopic Dermatitis (1993) Severity scoring of atopic dermatitis: the SCORAD index. Dermatology 186:23–31CrossRefGoogle Scholar
  36. 36.
    Frauman AG (1996) An overview of the adverse reactions to adrenal corticosteroids. Adverse Drug React Toxicol Rev 15:203–206PubMedGoogle Scholar
  37. 37.
    Martinati LC, Bertoldo F, Gasperi E, Fortunati P, Lo Cascio V, Boner AL (1998) Longitudinal evaluation of bone mass in asthmatic children treated with inhaled beclomethasone dipropionate or cromolyn sodium. Allergy 53:705–708PubMedCrossRefGoogle Scholar
  38. 38.
    Baraldi E, Bollini MC, De Marchi A, Zacchello F (1994) Effect of beclomethasone dipropionate on bone mineral content assessed by x-ray densitometry in asthmatic children: a longitudinal evaluation. Eur Respir J 7:710–714PubMedCrossRefGoogle Scholar
  39. 39.
    Wong CA, Walsh LJ, Smith CJ, Wisniewski AF, Lewis SA, Hubbard R, Cawte S, Green DJ, Pringle M, Tattersfield AE (2000) Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet 355(9213):1399–1403PubMedCrossRefGoogle Scholar
  40. 40.
    Langhammer A, Norjavaara E, de Verdier MG, Johnsen R, Bjermer L (2004) Use of inhaled corticosteroids and bone mineral density in a population based study: the Nord-Trondelag Health Study (the HUNT Study). Pharmacoepidemiol Drug Saf 13(8): 569–579PubMedCrossRefGoogle Scholar
  41. 41.
    Lipworth BJ (1999) Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 159:941–955PubMedCrossRefGoogle Scholar
  42. 42.
    Allen DB (2004) Systemic effects of inhaled corticosteroids in children. Curr Opin Pediatr 16:440–444PubMedCrossRefGoogle Scholar
  43. 43.
    Leone FT, Fish JE, Szefler SJ, West SL (2003) Systematic review of the evidence regarding potential complications of inhaled corticosteroid use in asthma: collaboration of American College of Chest Physicians, American Academy of Allergy, Asthma, and Immunology, and American College of Allergy, Asthma, and Immunology. Chest 124:2329–2340PubMedCrossRefGoogle Scholar
  44. 44.
    Halpern MT, Schmier JK, Van Kerkhove MD, Watkins M, Kalberg CJ (2004) Impact of long-term inhaled corticosteroid therapy on bone mineral density: results of a meta-analysis. Ann Allergy Asthma Immunol 92:201–207PubMedCrossRefGoogle Scholar
  45. 45.
    Mehta SS, Oz OK, Antich PP (1998) Bone elasticity and ultrasound velocity are affected by subtle changes in the organic matrix. J Bone Miner Res 13:114–121PubMedCrossRefGoogle Scholar
  46. 46.
    Specker BL, Schoenau E (2005) Quantitative bone analysis in children: current methods and recommendations. J Pediatr 146:726–731PubMedCrossRefGoogle Scholar
  47. 47.
    The WHO Study Group (1994) Assessment of fracture risk and its application to screening for menopausal osteoporosis. WHO Technical Report Series 843. WHO, GenevaGoogle Scholar
  48. 48.
    Frost ML, Blake GM, Fogelman I (2001) Quantitative ultrasound and bone mineral density are equally strongly associated with risk factors for osteoporosis. J Bone Miner Res 16:406–416PubMedCrossRefGoogle Scholar
  49. 49.
    Imamoto K, Saito N, Yamamura Y, Yamamura I (1996) Bone mineral density of the calcanei dissected from 30 cadavers: correlation of the values by the DXA, QCT and USD methods. Nippon Ronen Igakkai Zasshi 33:597–602PubMedGoogle Scholar
  50. 50.
    Luengo M, Picado C, Del Rio L, Guañabens N, Montserrat JM, Setoain J (1991) Vertebral fracture in steroid dependent asthma and involutional osteoporosis: a comparative study. Thorax 46: 803–806PubMedCrossRefGoogle Scholar
  51. 51.
    Van Staa TP, Leufkens HGM, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787PubMedCrossRefGoogle Scholar
  52. 52.
    Cepollaro C, Gonnelli S, Rottoli P, Montagnani A, Caffarelli C, Bruni D, Nikiforakis N, Fossi A, Rossi S, Nuti R (2005) Bone ultrasonography in glucocorticoid-induced osteoporosis. Osteoporos Int 16(7):743–748PubMedCrossRefGoogle Scholar
  53. 53.
    Tanaka H (2007) Secondary osteoporosis. Glucocorticoid induced osteoporosis in childhood: prophylaxis and treatment (in Japanese). Clin Calcium 17(7):1114–1119PubMedGoogle Scholar
  54. 54.
    Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Suzuki Y, Tanaka H, Fujiwara S, Miki T, Sagawa A, Nishizawa Y, Seino Y The Subcommittee to Study Diagnostic Criteria for Glucocorticoid-Induced Osteoporosis (2005) Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004). J Bone Miner Metab 23(2): 105–109PubMedCrossRefGoogle Scholar
  55. 55.
    Teitelbaum JE, Rodriguez RJ, Ashmeade TL, Yaniv I, Osuntokun BO, Hudome S, Fanaroff A (2006) Quantitative ultrasound in the evaluation of bone status in premature and full-term infants. J Clin Densitom 9(3):358–362PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2008

Authors and Affiliations

  • Jochen G. Mainz
    • 1
  • Dieter Sauner
    • 2
  • Ansgar Malich
    • 2
  • Stephanie John
    • 1
  • Heike Beyermann
    • 1
  • Hans-Joachim Mentzel
    • 2
  • Werner A. Kaiser
    • 2
  • Felix Zintl
    • 1
  1. 1.Department of Pediatrics (Pediatric Pulmonology)Friedrich-Schiller-University of JenaJenaGermany
  2. 2.Institute of Diagnostic and Interventional RadiologyFriedrich-Schiller-University of JenaJenaGermany

Personalised recommendations