Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.

Abstract

BACKGROUND:

No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis.

METHODS:

In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 μg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41).

FINDINGS:

We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10).

INTERPRETATION:

Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate.

FUNDING:

Lilly.

• Authors: David L Kendler, Fernando Marin, Cristiano A F Zerbini, Luis A Russo, Susan L Greenspan, Vit Zikan, Alicia Bagur, Jorge Malouf-Sierra, Péter Lakatos, Astrid Fahrleitner-Pammer, Eric Lespessailles, Salvatore Minisola, Jean Jacques Body, Piet Geusens, Rüdiger Möricke, Pedro López-Romero
• Journal: Lancet (London, England) (Lancet) Vol. 391 Issue 10117 Pg. 230-240 (01 20 2018) ISSN: 1474-547X [Electronic] England
• PMID: 29129436 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Bone Density Conservation Agents
• Teriparatide
• Risedronic Acid

Topics

• Aged
• Aged, 80 and over
• Americas (epidemiology)
• Bone Density (drug effects)
• Bone Density Conservation Agents (adverse effects, therapeutic use)
• Double-Blind Method
• Europe (epidemiology)
• Female
• Humans
• Incidence
• Middle Aged
• Osteoporosis, Postmenopausal (complications, drug therapy, epidemiology, physiopathology)
• Osteoporotic Fractures (diagnostic imaging, etiology, physiopathology, prevention & control)
• Radiography
• Risedronic Acid (adverse effects, therapeutic use)
• Teriparatide (adverse effects, therapeutic use)