Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teriparatide in Postmenopausal Women With Low Bone Mass

Abstract

Romosozumab is a monoclonal antibody that inhibits sclerostin and has been shown to reduce the risk of fractures within 12 months. In a phase II, randomized, placebo-controlled clinical trial of treatment-na€ ıve postmenopausal women with low bone mass, romosozumab increased bone mineral density (BMD) at the hip and spine by the dual effect of increasing bone formation and decreasing bone resorption. In a substudy of that trial, which included placebo and teriparatide arms, here we investigated whether those observed increases in BMD also resulted in improvements in estimated strength, as assessed by finite element analysis. Participants received blinded romosozumab s.c. (210 mg monthly) or placebo, or open-label teriparatide (20 mg daily) for 12 months. CT scans, obtained at the lumbar spine (n ¼ 82) and proximal femur (n ¼ 46) at baseline and month 12, were analyzed with finite element software (VirtuOst, O.N. Diagnostics) to estimate strength for a simulated compression overload for the spine (L 1 vertebral body) and a sideways fall for the proximal femur, all blinded to treatment assignment. We found that, at month 12, vertebral strength increased more for romosozumab compared with both teriparatide (27.3% versus 18.5%; p ¼ 0.005) and placebo (27.3% versus -3.9%; p < 0.0001); changes in femoral strength for romosozumab showed similar but smaller changes, increasing more with romosozumab versus teriparatide (3.6% versus -0.7%; p ¼ 0.027), and trending higher versus placebo (3.6% versus À0.1%; p ¼ 0.059). Compartmental analysis revealed that the bone-strengthening effects for romosozumab were associated with positive contributions from both the cortical and trabecular bone compartments at both the lumbar spine and hip. Taken together, these findings suggest that romosozumab may offer patients with osteoporosis a new bone-forming therapeutic option that increases both vertebral and femoral strength within 12 months.

FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab

“…In support of this, as has been shown in preclinical studies, romosozumab administration for 12 months in ovariectomized cynomolgus monkeys increased cortical and trabecular bone mass and thickness, and improved bone strength . Improvements in cortical thickness and increases in estimated bone strength of both cortical and trabecular bone at the spine and hip using CT and finite element analysis have also been observed in patients with postmenopausal osteoporosis receiving romosozumab …”

One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study

“…These observations suggest that attaining a higher BMD and improving bone microarchitecture within 1 year of romosozumab treatment (26)(27)(28)(29)(30)(31) is associated with rapid fracture risk reduction, which is sustained upon transition to antiresorptive therapy, and support the clinical benefit of rebuilding skeletal mass and structure (ie, the foundation effect) with romosozumab for 12 months resulting in fewer fractures upon transition to denosumab. (32) This sequence of therapy-a bone-forming agent first, followed by an antiresorptive agent-may be particularly beneficial for patients at high risk for fracture.…”

Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis

“…Romosozumab rapidly increased bone mineral density, a finding consistent with those of previous studies. 5,15 We found significantly greater gains with romosozumab than with alendronate at the lumbar spine, total hip, and femoral neck by month 6. After the transition to alendronate, the significant difference between treatment groups was maintained.…”