Elsevier

The Lancet

Volume 391, Issue 10117, 20–26 January 2018, Pages 230-240
The Lancet

Articles
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

https://doi.org/10.1016/S0140-6736(17)32137-2Get rights and content

Summary

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.

Introduction

Approved treatments for post-menopausal osteoporosis include anti-resorptive and bone-forming drugs. Anti-resorptive therapies target osteoclast-mediated bone resorption, thereby reducing bone loss, increasing bone mineral density (BMD), and reducing the risk of vertebral fractures.1 Nitrogen-containing bisphosphonates and denosumab can also reduce the risk of non-vertebral and hip fractures in post-menopausal women who have a high risk of fractures.2, 3 Teriparatide (recombinant human parathyroid hormone) is a bone-forming medication that preferentially stimulates osteoblasts to produce new bone tissue, thereby increasing bone mass and strength.4 Teriparatide reduces vertebral and non-vertebral fractures in post-menopausal women with established osteoporosis.5

Although several studies6, 7, 8, 9, 10, 11 have compared the effects of these two classes of drugs on surrogate markers of bone strength and quality (such as areal and volumetric bone mineral density, biochemical markers of bone turnover, static and dynamic histomorphometry, and finite element analysis estimates of bone strength), no adequately powered head-to-head studies have compared the effects of anti-resorptives and bone-forming drugs on reducing the risk of fractures as the primary outcome. Two clinical trials12, 13 have reported fracture outcomes in a head-to-head comparison of teriparatide and bisphosphonates, showing a greater reduction in the risk of new vertebral fractures with teriparatide than with oral bisphosphonates. However, fractures were secondary or exploratory outcomes in these studies.

We studied the effects of 24 months of treatment with teriparatide compared with risedronate on the incidence of new fractures in post-menopausal women with pre-existing vertebral fractures, regardless of previous osteoporosis treatment.

Section snippets

Study design

The VERtebral fracture treatment comparisons in Osteoporotic women (VERO) study was a randomised, double-blind, active-controlled, parallel-group trial done at 123 centres with experience in the management of patients with osteoporosis in 14 countries in Europe, South America, and North America. The first patient entered the study in October, 2012, and the last patient completed the study in July, 2016.

Research in context

Evidence before the study

Treatments for osteoporosis reduce the risk of

Results

683 patients were enrolled in each treatment group, 680 of whom in each group started treatment. 1013 (74·2%) of 1366 enrolled patients completed the trial (figure 1). Six patients (three in each treatment group) did not receive any study drug and were excluded from the analysis. Baseline demographics and clinical characteristics were similar between groups (table 1, appendix p 3). The overall mean age was 72·1 years (SD 8·7). Most patients were white. The mean number of prevalent vertebral

Discussion

In this study, involving post-menopausal women with severe osteoporosis at high risk of fracture, teriparatide was associated with a lower risk of new vertebral fractures than risedronate at 12 months and 24 months. A smaller percentage of patients in the teriparatide group had at least one non-vertebral fracture, in all of the predefined non-vertebral fracture categories, during 24 months, but there were no significant differences between groups. However, the total number of clinical fractures

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