Original articles
Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn’s disease

https://doi.org/10.1016/S1542-3565(04)00662-7Get rights and content

Background & Aims: Osteoporosis frequently occurs in Crohn’s disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. Methods: In 34 international centers, 272 patients with Crohn’s disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. Results: Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, −1.04% vs −3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. Conclusions: Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn’s disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

Section snippets

Materials and methods

An open, randomized, controlled trial was conducted in 34 centers in 8 European countries and Israel to compare budesonide CR capsules with oral prednisolone in patients with ileocecal Crohn’s disease. The primary aim of the study was to compare the changes in bone mineral density (BMD) between the 2 treatment modalities (also assessing lumbar spine fractures). In parallel, efficacy of the treatments and its safety and tolerability were assessed as secondary end points to balance clinically

Results

In total, 285 patients were randomized, of whom 272 received at least one dose of study drug and were analyzed (Figure 1). The efficacy analysis is based on 271 patients, because 1 patient did not have any “on treatment” data. Similar proportions of patients in both treatment arms remained in the study (at 6 months, budesonide 81% vs prednisolone 83%; at 12 months, budesonide 61% vs prednisolone 61%; at 24 months, budesonide 52% vs prednisolone 48%). Most withdrawals were the result of

Discussion

It has previously been shown that, at diagnosis, BMD in patients with Crohn’s disease is similar to that of the general population.32 The development of osteopenia, frequently seen at a later stage, could be a consequence of the disease itself or its treatment. The present study intended to explore whether topically acting glucocorticosteroids had advantages over prednisolone with respect to degradation of the bone matrix, with the condition that clinical efficacy should be comparable.

During

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  • Cited by (0)

    The study was performed in scientific collaboration with AstraZeneca Research and Development, Lund, Sweden, and financially supported by AstraZeneca Sweden. Dr Persson has been a full-time employee of AstraZeneca since 1982. Dr Hapten-White is a full-time employee of AstraZeneca. Dr Graffner is an employee of AstraZeneca. Dr Bianchi Porro has received financial support from AstraZeneca.

    Members of the MATRIX Study Group are listed in the Appendix.

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