Teriparatide outdoes risedronate in preventing recurrent vertebral fractures in post-menopausal women
A once-daily subcutaneous dose of teriparatide may be more effective than once-weekly oral risedronate in preventing vertebral fractures in post-menopausal women with osteoporosis and a history of vertebral fractures, findings from the VERO* trial show.
“Our study demonstrates … superior clinical and vertebral antifracture efficacy of teriparatide [vs risedronate] in post-menopausal women with existing vertebral fractures, showing the added value of teriparatide for the prevention of fragility fractures,” said the researchers.
“Clinicians should consider teriparatide for optimal management for patients with osteoporosis who have prevalent vertebral fractures.”
Participants in this multinational, double-blind study were post-menopausal women (mean age 72.1 years) with two or more moderate or one severe vertebral fracture and bone mineral density (BMD) T score ≤ -1.50 who were randomized to receive subcutaneous teriparatide injections (20 µg once daily) plus once-weekly oral placebo (n=680) or oral risedronate (35 mg once weekly) plus once-daily placebo injections (n=680) for 24 months. Patients were also given daily calcium and vitamin D supplements, while osteoporosis medications were discontinued at study entry barring a few exceptions.
The primary outcome was the percentage of patients with ≥1 new vertebral fracture, defined in this study as vertebral body height loss of ≥20 percent (and 4 mm) of a vertebra that was unfractured at baseline or ≥1 severity grade decrease in vertebral height for a pre-existing fracture.
At 24 months, incidence of new vertebral fractures was higher in the group receiving risedronate compared with teriparatide (12.0 percent [n=64] vs 5.4 percent [n=28]; risk ratio [RR], 0.44, 95 percent confidence interval [CI], 0.29–0.68; p<0.0001). [Lancet 2017;doi:10.1016/S0140-6736(17)32137-2]
The incidence of clinical fractures was also higher among women who received risedronate vs teriparatide (9.8 percent [n=61] vs 4.8 percent [n=30]; hazard ratio [HR], 0.48, 95 percent CI, 0.32–0.74; p=0.0009), though there was no significant difference between patients on risedronate and teriparatide with regards to nonvertebral fragility fractures (6.1 percent [n=38] vs 4.0 percent [n=25]; HR, 0.66, 95 percent CI, 0.39–1.10; p=0.10).
Patients in both groups experienced similar loss of height (mean, 0.6 vs 0.5 cm for teriparatide vs risedronate over the 24-month study period) as well as improvements in back pain and health-related quality of life.
Incidence of falls was also comparable between patients on teriparatide and risedronate (2.2 percent vs 2.8 percent; p=0.60). While incidence of ≥1 treatment-emergent adverse events was similar between patients on teriparatide and risedronate, pain in the extremities (5.4 percent vs 2.6 percent), hypercalcaemia (2.2 percent vs 0.1 percent), and dizziness (4.4 percent vs 1.8 percent) were more common among patients on teriparatide.
While there are some studies that suggest that treatment with teriparatide following “long-term exposure to potent antiresorptive drugs” may be linked to a decrease in BMD, and subsequently fractures at certain sites, the researchers highlight that the comparable results between patients on risedronate and teriparatide with regards to nonvertebral fractures “do not support that hypothesis”.
They acknowledged that the lack of measurement of BMD and bone turnover markers was a limitation. The lower serum vitamin D concentrations among patients on teriparatide, while unsurprising, may also warrant monitoring particularly in patients at risk for vitamin D deficiency, said the researchers.
“Although relatively small, this study provides some direct evidence that a bone-forming agent administered over 2 years can reduce the incidence of not only new vertebral fractures, but also clinical fractures, compared with a bisphosphonate,” said Professor Serge Ferrari from Geneva University Hospital, Geneva, Switzerland, in a commentary. [Lancet 2017;doi:10.1016/S0140-6736(17)32167-0]
“The findings therefore suggest that patients at high risk of fracture, particularly those at imminent risk [ie, with a recent fracture], should preferentially receive teriparatide rather than an oral bisphosphonate,” he said, though he cautioned against extrapolating these results to other bone-forming agents.