ArticlesZoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial
Introduction
Glucocorticoid drugs are a mainstay of treatment in many inflammatory and immune-mediated disorders.1 However, persistent use is associated with side-effects, such as bone loss and increased fracture risk.2, 3, 4, 5, 6 This increased risk is apparent in some patients within 3 months of starting glucocorticoids.4, 7
Prevention and treatment of glucocorticoid-induced osteoporosis is best established for bisphosphonates,5 a class of drugs that increase bone mineral density and reduce vertebral fracture risk in patients beginning or continuing glucocorticoid treatment.8, 9, 10 Daily oral bisphosphonate therapy has been approved for the treatment and prevention of glucocorticoid-induced osteoporosis, but compliance and adherence with daily and weekly therapy is characteristically suboptimum.11, 12, 13, 14 An association between poor adherence or compliance and increased fracture risk has been documented in women with postmenopausal osteoporosis who were treated with bisphosphonate.15, 16
Zoledronic acid is a potent bisphosphonate; when given every year by intravenous infusion, the drug increases bone mineral density and reduces fracture risk in women with postmenopausal osteoporosis.17 It also reduces subsequent fractures in patients who have had an osteoporosis-related fracture, and increases survival in those who have sustained a low-trauma hip fracture.18 We present the results of HORIZON (Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly): a 1-year, multicentre, double-blind, double-dummy randomised controlled trial designed to establish whether one 5 mg infusion of zoledronic acid is non-inferior to the licensed dose of risedronate (5 mg daily) for the prevention and treatment of glucocorticoid-induced osteoporosis.
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Participants
Men and women aged 18–85 years were eligible for inclusion in the study if they were receiving at least 7·5 mg oral prednisolone daily (or equivalent) and were expected to receive glucocorticoids for at least another 12 months. Patients were enrolled from 54 centres in 16 countries (Australia, Belgium, Czech Republic, Estonia, Finland, France, Hong Kong, Hungary, Israel, Lithuania, Poland, Romania, Spain, Switzerland, UK, and USA), and the study took place in teaching and community hospitals
Results
Figure 1 shows the trial profile. The treatment subgroup enrolled 545 patients and the prevention subgroup enrolled 288. Overall, 93% (n=771 patients) of enrolled patients completed the study (treatment 94% [n=511], prevention 90% [n=260]).
Table 1 shows baseline characteristics of patients taking zoledronic acid or risedronate. Overall, 68% (n=568) of participants were women, of whom 66% (n=373) were menopausal. 82% (n=304) of menopausal women had reached menopause more than 5 years earlier
Discussion
We have shown that one 5 mg infusion of zoledronic acid increases bone mineral density of the lumbar spine and femoral neck, trochanter, and total hip more than does 5 mg oral risedronate daily in patients already taking glucocorticoids. The enhanced effectiveness of zoledronic acid was evident within 6 months of starting treatment. The increases in lumbar spine bone mineral density induced by risedronate are of similar magnitude to those reported previously for glucocorticoid-induced
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