T-score as an Indicator of Fracture Risk on Therapy: Evidence From Romosozumab vs Alendronate Treatment in the ARCH Trial

Introduction BMD is a strong predictor of fracture (fx) risk in untreated patients. Recent evidence suggests that BMD achieved during treatment also reflects fx risk; thus, T-scores are being considered as a target to guide osteoporosis treatment. In ARCH (NCT01631214), romosozumab (Romo), an investigational bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption, followed by alendronate (ALN) had greater efficacy in fx risk reduction and BMD gains vs ALN alone (Saag NEJM 2017). Of note, a cardiovascular imbalance was observed with Romo in ARCH and a comprehensive assessment of these data is ongoing. Here we explored the relationship between T-scores achieved on-study after 1 year with Romo or ALN and subsequent fx risk.

Methods Postmenopausal women with osteoporosis and prior fragility fx were randomized 1:1 to receive Romo 210 mg SC QM or ALN 70 mg PO QW for 12 months, followed by open-label (OL) ALN 70 mg PO QW for ≥12 months, with an event-driven primary analysis. We examined 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 (NVT) fx rates. We also compared fxs in the OL period, including new vertebral (VT) fxs in year 2 (based on month 24 spine radiographs) and clinical, NVT, and hip fxs between arms in the full OL period.

Results ARCH enrolled 4093 patients (2046 Romo, 2047 ALN); mean baseline T-scores were – 2.96 at the lumbar spine and – 2.80 at the TH. 3465 patients (1739 Romo, 1726 ALN) received ≥ 1 OL ALN dose in the OL period (median 1.9 years follow-up). Mean TH BMD increased by 6.2 % for Romo and 2.8 % for ALN 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 NVT fx rate observed in the OL period (Figure) and the relationship was independent of the drug received in the first year. During the OL period, when all patients were on ALN, patients who received Romo first had a 75 % lower relative risk of new VT fx (P < 0.001), and had reductions in clinical (32 %, P = 0.001), NVT (19 %, P = 0.120), and hip (40 %, P = 0.041) fxs vs patients who received ALN first.

Discussion Higher absolute TH T-scores achieved on therapy at month 12 resulted in subsequent lower fx risk regardless of the treatment recieved, with ongoing benefits from building a BMD foundation. These data support the concept of a T-score target to improve outcomes in osteoporosis treatment.

Conflict of interest Funding: Amgen Inc., Astellas, and UCB Pharma

Korrespondenzadresse Derk Pannen, UCB Pharma GmbH, Alfred-Nobel-Str. 10, 40789 Monheim, Deutschland, E-Mail: [e-mail]