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

I A Campbell¹, J G Douglas², R M Francis³, R J Prescott⁴, D M Reid⁵ on behalf of the Research Committee of the British Thoracic Society

¹ Department of Respiratory Medicine, Llandough Hospital, Penarth, UK
² Department of Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen, UK
³ Musculoskeletal Division, University of Newcastle, Newcastle, UK
⁴ Department of Medical Statistics, University of Edinburgh, UK
⁵ Department of Medicine & Therapeutics, University of Aberdeen, UK

Correspondence to:
Correspondence to:
Dr I A Campbell
Llandough Hospital, Penarth, Vale of Glamorgan CF64 2XX, UK; ian.campbell{at}cardiffandvale.wales.nhs.uk

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.

Keywords: etidronate; calcium; osteoporosis; asthma; glucocorticoids

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