Post hoc analysis of FRAME and ARCH revealed that on-study nonvertebral and vertebral fractures by Month 12 were less common in women initially treated with romosozumab versus placebo or alendronate. Recurrent fracture risk was also lower in romosozumab‑treated patients, and there were no fracture‑related complications. Results support continuing romosozumab treatment post‑fracture. Post hoc analysis evaluating efficacy and safety of romosozumab, administered in the immediate post‑fracture period, in the FRAME and ARCH phase 3 trials. In FRAME (NCT01575834) and ARCH (NCT01631214), postmenopausal women with osteoporosis were randomized 1:1 to romosozumab 210 mg monthly or comparator (FRAME, placebo; ARCH, alendronate 70 mg weekly) for 12 months, followed by antiresorptive therapy (FRAME, denosumab; ARCH, alendronate). In patients who experienced on-study nonvertebral or new/worsening vertebral fracture by Month 12, we report the following: fracture and treatment‑emergent adverse event (TEAE) incidence through 36 months, bone mineral density changes (BMD), and romosozumab timing. Due to the sample sizes employed, meaningful statistical comparisons between treatments were not possible. Incidence of on-study nonvertebral and vertebral fractures by Month 12 was numerically lower in romosozumab- versus comparator-treated patients (FRAME, 1.6

We comprehensively described elderly Medicare women with an outpatient visit in 2011 and fracture within 2 years before. These women were at very high risk for subsequent fracture and high healthcare utilization and cost, especially those with vertebral or multiple fractures. However, rates of fracture prevention treatments were low.INTRODUCTION:Postmenopausal women with osteoporosis are stratified to high and very-high fracture risk categories, and this categorization drives algorithms for osteoporosis management in osteoporosis treatment guidelines. This study comprehensively describes a very-high-risk cohort.METHODS:This retrospective cohort study used the Medicare 20% database; elderly women with an outpatient visit in 2011 and fracture within 2 years before the visit were included. Outcomes included fracture risk, all-cause and fracture-related healthcare resource utilization and cost, and osteoporosis medication use in the 5 years after the visit.RESULTS:Overall, 43,193 patients were included. The 5-year probability was 0.36 for major fracture and 0.11 and 0.17 for hip fracture and vertebral fracture, respectively, much higher than the guidelines' 10-year probability thresholds for very-high-risk (0.3 for major fracture, 0.045 for hip fracture). Rates of hospitalizations, emergency department visits or observation stays, and skilled nursing facility stays in year 1 were 53.7, 57.0, and 18.8 per 100 patient-years, respectively, decreasing slightly in subsequent years. Mean healthcare cost was $23,700 in year 1, decreasing to $18,500 in year 5. About 29.1% of patients received osteoporosis medications in year 1, decreasing to 16.9% by year 5. Rates for all outcomes, especially fractures, were much higher among vertebral and multiple fracture cohorts.CONCLUSION:Elderly women with a fracture within last 2 years were at very-high-risk for subsequent fracture and high healthcare utilization and cost, especially those with vertebral or multiple fractures. However, rates of fracture prevention treatments were low. More effort is needed to identify and treat patients at very-high-risk for fracture.

Background Romosozumab (ROMO) inhibits sclerostin and has a dual effect on bone, increasing formation while decreasing resorption, resulting in significant increases in bone mineral density (BMD) at 6 months (m), which at 12m reach 13.3% vs placebo (PBO) at the spine.1 Using high resolution quantitative computed tomography, BMD increases were observed at both trabecular and cortical compartments of the spine, explaining the significant reductions in radiographic vertebral fracture (VFx) risk in women with osteoporosis (OP) enrolled in the FRAME trial (NCT01575834). Objectives Here, we report the effect of ROMO on clinical (clin) VFx incidence over 12m in women in FRAME with back pain. Methods FRAME enrolled 7180 postmenopausal women with OP, mean age 70.9 yrs (total hip T-score –2.5 to –3.5) and no severe VFx. Patients received monthly ROMO (n=3589; 210mg) or PBO (n=3591) for 12m. At monthly visits, women with back pain consistent with a clin VFx had a confirmatory spinal X-ray. Clin VFx risk (ROMO vs PBO) was calculated by Cox-proportional hazards model. Results Of 119 women reporting back pain over 12m, 20 women were diagnosed with a new or worsening VFx. With ROMO, 3 clin VFx (<0.1%; all at <2m) were identified vs 17 (0.5% at 12m) with PBO (Figure). Clin VFx risk was 83% lower in the ROMO group vs PBO at 12m (hazard ratio 0.17; 95% CI, 0.05–0.58; p=0.001). In women with clin VFx vs no clin VFx, the lumbar spine T-score was numerically lower and the FRAX score higher at baseline; other baseline characteristics were comparable among all women who reported back pain. Conclusions ROMO treatment for 12m was associated with rapid and large reductions in clin VFx risk vs PBO. In the ROMO group, all clin VFx occurred <2m; clin VFx risk was ≥5 times higher with PBO vs ROMO. Monthly study visits in FRAME allowed for timely radiologic confirmation of a suspected clin VFx. References Cosman F et al. N Engl J Med 2016;375:1532–43. Acknowledgements Funded by Amgen Inc. and UCB Pharma. Disclosure of Interest P. Geusens Grant/research support from: Amgen, Pfizer, MSD, UCS, Abbott, Eli Lilly, BMS, Novartis, Roche, Will-Pharma, Consultant for: Amgen, Speakers bureau: Amgen, M. Oates Grant/research support from: Amgen, Speakers bureau: Amgen, Eli Lilly, A. Miyauchi Consultant for: Amgen, Astellas BioPharma, J. Adachi Grant/research support from: AbbVie, Amgen, Eli Lilly, Merck, Pfizer, Consultant for: Amgen, Merck, Speakers bureau: Amgen, M. Lazaretti-Castro Grant/research support from: Amgen, Consultant for: Amgen, Eli Lilly, Sanofi, Speakers bureau: Sanofi, P. Ebeling Grant/research support from: Amgen, Merck, Eli Lilly, Consultant for: Amgen, Eli Lilly, Radius, C. A. Perez Nino Shareholder of: UNIENDO – Clinical Research, Employee of: UNIENDO – Clinical Research, C. Milmont Shareholder of: Amgen, Employee of: Amgen, A. Grauer Shareholder of: Amgen, Employee of: Amgen, C. Libanati Shareholder of: UCB Pharma, Employee of: UCB Pharma