Objective: To date, no controlled, head-to-head clinical trials have compared the anti-fracture efficacy of osteoporosis therapies as the primary endpoint. This study compared the anti-fracture efficacy of teriparatide (TPTD) with risedronate (RIS) in postmenopausal women with severe osteoporosis.

Patients and Methods: 2-year randomized (1:1), double-blind, double-dummy trial. We compared subcutaneous daily TPTD (20 µg) with oral weekly RIS (35 mg) in 1,360 women (mean age [SD]: 72.1 [8.7] years) with at least 2 moderate or 1 severe vertebral fracture and low bone mass. Prior use of osteoporosis drugs was allowed. The primary endpoint was incidence of new vertebral fractures after 2 years assessed by quantitative morphometry. Secondary outcomes were clinical fractures, non-vertebral fractures, other spine fractures endpoints, height loss, back pain, quality of life (EQ-5D), and safety.

Results: Fewer patients receiving TPTD compared to RIS had new vertebral fractures at 2 years (5.4% vs 12.0%, p<0.0001), and after 1 year (3.1% vs 6.0%, p<0.05). Fewer patients receiving TPTD compared to RIS had moderate/severe (≥1) vertebral fractures (5.0% vs 11.8%, p<0.001), multiple (≥2) vertebral fractures (0.4% vs 2.3, p<0.01), clinical vertebral plus non-vertebral fragility fractures (4.8% vs 9.8%, p<0.001), and non-vertebral fragility fractures (4.0% vs 6.1%, p=0.099). Groups did not differ in change from baseline in height, back pain, and quality of life. More patients in the TPTD group had at least 1 report of hypercalcemia (8.8% vs 0.2%), hyperuricemia (13.0% vs 3.3%), and hypomagnesemia (5.2% vs 0.7%) (all p<0.001).

Conclusions: Among postmenopausal women with severe osteoporosis, the risk for new vertebral and clinical fractures was significantly reduced in patients receiving TPTD compared to those receiving RIS.