Post-hoc analysis of the ARCH study1 to explore the relationship between T-scores achieved after 1 year with romosozumab or alendronate and subsequent fracture rates.
Postmenopausal women with osteoporosis and prior fragility fracture were randomised 1:1 to romosozumab 210mg SC QM or alendronate 70mg PO QW for 12 months, followed by open-label (OL) alendronate for ≥12 months. Change from baseline in BMD and T-scores at 12 months and the relationship between total hip (TH) T-scores at month 12 and subsequent nonvertebral fracture rates were examined. Fractures in the OL period, including new vertebral fractures in year 2 and clinical, nonvertebral and hip fratures between arms in OL period were also compared
ARCH enrolled 4093 patients, mean baseline T-scores were -2.96 at the lumbar spine and -2.80 at the TH. 3465 patients received ≥1 alendronate dose in the OL period (median 1.9 years follow-up). Mean TH BMD increased by 6.2% for romosozumab and 2.8% for alendronate in the first year, with increases in T-score of 0.31 and 0.15, respectively. At month 12, the achieved TH T-score was associated with the 1-year nonvertebral fracture rate observed in the OL period (Figure), the relationship was independent of the drug received in the first year. During the OL period, when all patients were on alendronate, patients who received romosozumab first had a 75% lower relative risk of new vertebral fracture (p<0.001), and had reductions in clinical (32%, p=0.001), nonvertebral (19%, p=0.120), and hip (40%, p=0.041) fractures versus patients who received alendronate first.
Higher absolute TH T-scores achieved on therapy at month 12 resulted in subsequent lower fracture risk regardless of treatment received, with ongoing benefits from building a BMD foundation. These data support the concept of a T-score target to improve outcomes in osteoporosis treatment.
Funding: Amgen Inc., Astellas, and UCB Pharma