Purpose: Recent evidence suggests treatment-achieved BMD is a reliable surrogate for fracture risk reduction. In ARCH (NCT01631214), Romo (bone-forming agent) followed by ALN achieved greater BMD gains and fracture risk reduction vs ALN alone. Here, we assess lumbar spine (LS) BMD and bone strength improvements by QCT and FEA.
Methods: Postmenopausal women with osteoporosis and prior vertebral/hip fracture received Romo 210mg SC monthly or ALN 70mg PO weekly for 12 months (1:1), followed by open-label ALN 70mg PO weekly. In an imaging substudy, LS BMD was assessed by QCT and vertebral-estimated bone strength by FEA using QCT images obtained at baseline (BL) and months 6, 12, and 24. Correlation analyses evaluated the relationship between changes in FEA, QCT, and DXA.
Results: Post-hoc analysis included 90 subjects (49 Romo;41 ALN) with BL and ≥1 post-BL QCT/FEA assessment. At BL, mean (SD) age was 73 (7) years; LS, total hip, femoral neck DXA T-scores were 3.08 (1.09), –2.70 (0.68), –2.84 (0.45); and 97% had prior vertebral fracture, similar to core study. Both groups experienced significant integral and trabecular BMD gains from BL at all time points (except ALN in trabecular BMD; Fig and data not shown). Romo and ALN differences were significant at months 6, 12, and 24. QCT BMD increases were accompanied by significant LS bone strength increases in both groups at all time points; Romo increases significantly greater. Correlation between post-BL FEA change and QCT BMD (integral and trabecular) and DXA was similar (combined treatment arms; r=0.69–0.87, all p<0.001).
Conclusions: Romo significantly improved LS BMD (QCT) and bone strength (FEA) vs ALN. Effects were rapid (month 6), sustained (over 12 months), preserved upon transition (through 24 months), and consistent with greater fracture risk reduction observed in this trial with Romo-ALN vs ALN.
Funding: Amgen Inc., Astellas, and UCB Pharm