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Thorax 59:761-768 doi:10.1136/thx.2003.013839
  • Asthma

Five year study of etidronate and/or calcium as prevention and treatment for osteoporosis and fractures in patients with asthma receiving long term oral and/or inhaled glucocorticoids

  1. I A Campbell1,
  2. J G Douglas2,
  3. R M Francis3,
  4. R J Prescott4,
  5. D M Reid5,
  6. on behalf of the Research Committee of the British Thoracic Society
  1. 1Department of Respiratory Medicine, Llandough Hospital, Penarth, UK
  2. 2Department of Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen, UK
  3. 3Musculoskeletal Division, University of Newcastle, Newcastle, UK
  4. 4Department of Medical Statistics, University of Edinburgh, UK
  5. 5Department of Medicine & Therapeutics, University of Aberdeen, UK
  1. Correspondence to:
    Dr I A Campbell
    Llandough Hospital, Penarth, Vale of Glamorgan CF64 2XX, UK; ian.campbellcardiffandvale.wales.nhs.uk
  • Received 29 July 2003
  • Accepted 7 February 2004

Abstract

Background: Glucocorticoids are associated with a reduction in bone density and an increased risk of fracture. Concurrent treatment with bisphosphonates reduces bone loss and may prevent fractures. A randomised study was performed to determine whether treatment with cyclical etidronate and/or calcium for 5 years prevents fractures or reverses/reduces bone loss in patients receiving glucocorticoid treatment for asthma.

Methods: A multicentre, randomised, parallel group comparison of etidronate alone, calcium alone, etidronate + calcium, and no treatment, with stratification according to level of glucocorticoid exposure was carried out in 39 chest clinics in the UK. Three hundred and forty nine postmenopausal female and male outpatients with asthma aged 50–70 years were randomised. The main outcome measures were fractures and changes in bone mineral density (BMD).

Results: Overall, 8% of the patients experienced symptomatic fractures and 17.5% developed either a symptomatic fracture and/or a semiquantitative vertebral fracture by the end of 5 years There were no significant differences between the four treatment groups. Comparing etidronate with no etidronate, the rates of new fractures were not significantly different for symptomatic fractures (OR 1.07 (95% CI 0.46 to 2.47)) or for any fractures (OR 0.82 (95% CI 0.45 to 1.47)). For the comparison of calcium with no calcium the corresponding ORs were 1.43 (95% CI 0.62 to 3.33) and 0.91 (95% CI 0.50 to 1.63). In post hoc analysis the effect of etidronate was greater in women than in men (interaction p value 0.02) with the fracture incidence roughly halved (OR 0.39, 95% CI 0.14 to 0.99). Etidronate increased BMD at the lumbar spine by 4.1% (p = 0.001) while calcium had no significant effect. At the proximal femur the effects of treatment were not significant (relative increases etidronate 1.6%; calcium 1.1%). The rate of new fractures in patients with fractures at entry (23.7%) was higher than in those without fractures at entry (14.3%): OR 1.87 (95% CI 1.06 to 3.07). No association was found between change in BMD and new fractures.

Conclusions: In patients receiving glucocorticoids for asthma etidronate significantly increased BMD over 5 years at the lumbar spine but not at the hip and had little if any protective effect against fractures, except possibly in postmenopausal women. The effects of calcium were not significant. Combination treatment had no advantage but increased unwanted effects.

Footnotes

  • The study was funded with an unrestricted grant to the Research Committee from Allen and Hanburys and Glaxo.

  • The study was coordinated by a subcommittee of the Research Committee whose members were: Drs I A Campbell (chairman and coordinating physician), P Bardsley (1993), J G Douglas, R M Francis, F J C Millard (1991–93), M D L Morgan (1991–97; associate coordinating physician 1992–93), Professors R J Prescott (statistician), D W Purdie (1991–2000) and D M Reid (2000–). Dr Alison Black performed the morphometry measurements and visual identification of fractures. The writing group consisted of the listed authors.

    The Research Committee of the British Thoracic Society would like to thank the following physicians and their staff without whose efforts and support the study would not have been possible: Dr P B Anderson, Sheffield General Hospital; Dr A G Arnold, Hull Royal Infirmary; Dr A Axford, Machynlleth Hospital; Dr S Banham, Glasgow Royal Infirmary; Dr J R M Bateman, Derby City Hospital; Dr M Bone, The Guest Hospital; Dr I A Campbell, Llandough Hospital; Dr A G Chappell, Bridgend General Hospital; Dr J Choo-Kang, Victoria Hospital; Dr R Clark, Queen Alexandra Hospital; Dr C K Connolly, Darlington Memorial Hospital; Dr J B Cookson, Glenfield Hospital; Dr I I Coutts, Treliske Hospital; Dr A C Davidson, Newham General Hospital; Dr P D O Davies, Fazakerley Hospital; Dr R G Dent, Queen Elizabeth II Hospital; Dr S Evans; St Mary’s Hospital; Dr A G Fennerty, Southern General Hospital; Dr M A Greenstone, Hull Royal Infirmary; Dr J W Hadfield, Whitworth Hospital; Dr R N Harrison, North Tees General Hospital; Dr J P R Hartley, Brighton General Hospital; Dr M R Hetzel, The Whittington Hospital; Dr C E Johnson, Pendle Community Hospital; Dr R Lowry, Belfast City Hospital; Dr C Luken, The Whittington Hospital; Dr A W Matthews, Queen Alexandra Hospital; Dr W G Middleton, Bangour General Hospital; Dr A C Miller, Mayday University Hospital; Dr E Millar, Southern General Hospital; Dr M D L Morgan, Glenfield Hospital; Dr E Neville, St Mary’s Hospital; Dr D Ornadel, The Whittington Hospital; Dr T O’Shaughnessy, Shrewsbury Road. Health Centre; Dr J F O’Reilly, Victoria Hospital; Dr D Parry, Bridgend General Hospital; Dr K Patel, Gartnavel General Hospital; Dr A Peacock, Gartnavel General Hospital; Dr M D Peake, Pontefract Infirmary; Professor D Shale, Llandough Hospital; Dr R Smith, Victoria Hospital; Dr D Spence, Friarage Hospital; Dr B H Stack, Gartnavel Hospital; Dr A H Sulliman, Newham General Hospital; Dr H Taggart, Belfast City Hospital; Dr S Tilzey, Sheffield General Hospital; Dr J Thomas, Machynlleth Hospital; Dr J A Turner, Royal Bournemouth Hospital; Dr C W G Turton, Brighton General Hospital; Dr J Warren, St Margaret’s Hospital; Dr T J Williams, Kettering General Hospital.