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Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial.
Lancet. 2009 Apr 11; 373(9671):1253-63.Lct

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.

Authors+Show Affiliations

University of Aberdeen, Aberdeen, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19362675

Citation

Reid, David M., et al. "Zoledronic Acid and Risedronate in the Prevention and Treatment of Glucocorticoid-induced Osteoporosis (HORIZON): a Multicentre, Double-blind, Double-dummy, Randomised Controlled Trial." Lancet (London, England), vol. 373, no. 9671, 2009, pp. 1253-63.
Reid DM, Devogelaer JP, Saag K, et al. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet. 2009;373(9671):1253-63.
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. (2009). Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet (London, England), 373(9671), 1253-63. https://doi.org/10.1016/S0140-6736(09)60250-6
Reid DM, et al. Zoledronic Acid and Risedronate in the Prevention and Treatment of Glucocorticoid-induced Osteoporosis (HORIZON): a Multicentre, Double-blind, Double-dummy, Randomised Controlled Trial. Lancet. 2009 Apr 11;373(9671):1253-63. PubMed PMID: 19362675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. AU - Reid,David M, AU - Devogelaer,Jean-Pierre, AU - Saag,Kenneth, AU - Roux,Christian, AU - Lau,Chak-Sing, AU - Reginster,Jean-Yves, AU - Papanastasiou,Philemon, AU - Ferreira,Alberto, AU - Hartl,Florian, AU - Fashola,Taiwo, AU - Mesenbrink,Peter, AU - Sambrook,Philip N, AU - ,, PY - 2009/4/14/entrez PY - 2009/4/14/pubmed PY - 2009/4/25/medline SP - 1253 EP - 63 JF - Lancet (London, England) JO - Lancet VL - 373 IS - 9671 N2 - 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/19362675/Zoledronic_acid_and_risedronate_in_the_prevention_and_treatment_of_glucocorticoid_induced_osteoporosis__HORIZON_:_a_multicentre_double_blind_double_dummy_randomised_controlled_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(09)60250-6 DB - PRIME DP - Unbound Medicine ER -