Research in context
Evidence before the study
Treatments for osteoporosis reduce the risk of
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.
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
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
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