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Cited by 527Bone health and osteoporosis researchBone health and treatmentsMenopause: Health Impacts and Treatments

Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial

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Reid, David M, Devogelaer, Jean-Pierre, Saag, Kenneth, Roux, Christian, Lau, Chak-Sing, Reginster, Jean-Yves, Papanastasiou, Philemon, Ferreira, Alberto +4 more·2009·The Lancet
DOI 10.1016/s0140-6736(09)60250-6
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Abstract

Background Persistent use of glucocorticoid drugs is associated with bone loss and increased fracture risk. Concurrent oral bisphosphonates increase bone mineral density and reduce frequency of vertebral fractures, but are associated with poor compliance and adherence. We aimed to assess whether one intravenous infusion of zoledronic acid was non-inferior to daily oral risedronate for prevention and treatment of glucocorticoid-induced osteoporosis.Methods This 1-year randomised, double-blind, double-dummy, non-inferiority study of 54 centres in 12 European countries, Australia, Hong Kong, Israel, and the USA, tested the effectiveness of 5 mg intravenous infusion of zoledronic acid versus 5 mg oral risedronate for prevention and treatment of glucocorticoid-induced osteoporosis. 833 patients were randomised 1:1 to receive zoledronic acid (n=416) or risedronate (n=417). Patients were stratified by sex, and allocated to prevention or treatment subgroups dependent on duration of glucocorticoid use immediately preceding the study. The treatment subgroup consisted of those treated for more than 3 months (272 patients on zoledronic acid and 273 on risedronate), and the prevention subgroup of those treated for less than 3 months (144 patients on each drug). 62 patients did not complete the study because of adverse events, withdrawal of consent, loss to follow-up, death, misrandomisation, or protocol deviation. The primary endpoint was percentage change from baseline in lumbar spine bone mineral density. Drug efficacy was assessed on a modified intention-to-treat basis and safety was assessed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00100620.Findings Zoledronic acid was non-inferior and superior to risedronate for increase of lumbar spine bone mineral density in both the treatment (least-squares mean 4.06% [SE 0.28] vs 2.71% [SE 0.28], mean difference 1.36% [95% CI 0.67-2.05], p=0.0001) and prevention (2.60% [0.45] vs 0.64% [0.46], 1.96% [1.04-2.88], p<0.0001) subgroups at 12 months. Adverse events were more frequent in patients given zoledronic acid than in those on risedronate, largely as a result of transient symptoms during the first 3 days after infusion. Serious adverse events were worsening rheumatoid arthritis for the treatment subgroup and pyrexia for the prevention subgroup.Interpretation A single 5 mg intravenous infusion of zoledronic acid is non-inferior, possibly more effective, and more acceptable to patients than is 5 mg of oral risedronate daily for prevention and treatment of bone loss that is associated with glucocorticoid use.

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  • In clinical practice, both bisphosphonates and PTH increase spine BMD to a greater extent than hip BMD.

    “In clinical practice, both bisphosphonates and PTH increase the spine BMD to a greater extent than the hip BMD [12, 14, 47, 50-53].”

    From Prevention of glucocorticoid induced bone changes with beta-ecdysone (2015) · cites this paper as [12]

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Authors
Reid, D. M., Devogelaer, J.-P., Saag, K., Roux, C., Lau, C.-S., Reginster, J.-Y., Papanastasiou, P., Ferreira, A., Hartl, F., Fashola, T., Mesenbrink, P., & Sambrook, P. N.
Affiliations
  • University of Aberdeen (GB)
  • UCLouvain (BE)
  • University of Alabama at Birmingham (US)
  • Université Paris Descartes (FR)
  • University of Dundee (GB)
  • University of Liège (BE)
  • Novartis (Switzerland) (CH)
  • F. Hoffmann-La Roche AG (CH)
  • The University of Sydney (AU)
Corresponding author
Reid, David M
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2009-04
Volume
373
Issue
9671
Pages
1253-1263
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(09)60250-6
OpenAlex
W2095741166
Cited by
527
References
36
Citations by year
2026: 7 · 2025: 20 · 2024: 27 · 2023: 20 · 2022: 24 · 2021: 39 · 2020: 24 · 2019: 26 · 2018: 23 · 2017: 25 · 2016: 26 · 2015: 32 · 2014: 23 · 2013: 36 · 2012: 39
FWCI
60.60
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
  • University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
  • Digital Access to Libraries (submittedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
  • Lithuanian University of Health Sciences (submittedVersion)
  • ORBi (University of Liège) (submittedVersion)
Funders
National Institute for Health and Care Research (NF-SI-0508-10082)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Oncology › Bone health and treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords
glucocorticoid-induced osteoporosis, zoledronic acid, risedronate, bisphosphonates, intravenous bisphosphonates, bone mineral density, lumbar spine, non-inferiority, osteoporosis prevention, osteoporosis treatment, fracture risk, drug safety, adverse events, medication adherence, horizon
MeSH terms
Risedronic Acid, Zoledronic Acid, Administration, Oral, Adolescent, Adult, Aged, Aged, 80 and over, Analysis of Variance, Diphosphonates, Double-Blind Method, Drug Administration Schedule, Female, Glucocorticoids, Humans, Imidazoles, Infusions, Intravenous, Male, Middle Aged, Osteoporosis, Etidronic Acid, Bone Density, Least-Squares Analysis, Treatment Outcome, Bone Density Conservation Agents, Young Adult

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