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.
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