Background/Purpose: The VERO trial was an active-controlled fracture endpoint clinical trial that recruited postmenopausal women with low bone mass and prevalent vertebral fractures (VFx). We have reported that the risk of new VFx and clinical fractures [a composite of clinical VFx and non-vertebral fragility fractures (NVFFx)] in patients treated with teriparatide (TPTD) compared with those treated with risedronate (RIS) was reduced by 56% and 52% respectively (p<.001 for each), with a non-significant reduction in NVFFx (34%, p=0.099). Here we present the pre-specified exploratory analysis of clinical vertebral fracture (ClinVFx) incidence over 24 months.

Methods: 1,360 postmenopausal women (680/arm; mean age: 72.1 years) with at least 2 moderate or 1 severe VFx and low bone mass (BMD T-score ≤-1.5) were randomized to TPTD 20 µg sc/day or RIS (35 mg po/week) in a 2-year, double-blind, double-dummy trial. A ClinVFx was defined as an clinical episode associated with signs and symptoms  suggestive of a VFx, such as acute onset of severe back pain, pain with little or no exertion or pain localised to a specific vertebra and associated with limited back mobility, confirmed with a new or worsened radiographic VFx (centrally adjudicated). A new vertebral fracture was radiologically defined as a loss of vertebral body height of at least 20% and 4 mm from the baseline radiograph by quantitative morphometry measurements, confirmed with a semiquantitative assessment (i.e.; the vertebral body also has an increase of 1 or more severity grade according to the Genant scale). Cumulative incidences of the first ClinVFx were obtained by Kaplan-Meier, and comparison was based on a stratified long-rank test. The stratified HR was computed from the log-rank test. Incidence rates, depicted as number of events per 100 patient-years, were also assessed.

Results: The mean (SD) number of prevalent VFx was 2.7 (2.1), 55.4% of the women had a BMD T-score <-2.5 (lowest value measured at the lumbar spine or hip), 36.5% a history of ClinVFx within the year before randomization, 27.9% were naïve to osteoporosis medications, and 57.9% were previously treated with bisphosphonates. A total of 31 women were diagnosed with an incident ClinVFx over the 24-month study duration: 7 women in the TPTD group (1.1%) compared to 24 women (3.9%) in the RIS group (hazard ratio: 0.29; 95% CI: 0.14-0.58; p=0.002) (Figure). The incidence rates (95% CI) were 0.58 (0.23-1.18) and 1.97 (1.27-2.91) events/patient-years in the TPTD and RIS treated subjects, respectively (p=0.004).

Conclusion: In postmenopausal women with severe osteoporosis, TPTD treatment for 24 months significantly reduced by 71% the risk of new clinical vertebral fractures compared with RIS.