Madrid, Spain—Among postmenopausal women with osteoporosis, 12-month treatment with romosozumab led to rapid and large reductions in risk for vertebral fracture compared with placebo, according to results from the phase 3 FRAME (Fracture Study in Postmenopausal Women with Osteoporosis) clinical trial. Romosozumab, a monoclonal antibody that binds and inhibits the glycoprotein sclerostin, belongs to a new class of drugs, explained FRAME lead investigator Piet Geusens, MD, PhD, Rheumatology Department, Maastricht University Medical Centre, Minderbroedersberg, The Netherlands, at the 2017 European League Against Rheumatism (EULAR) annual meeting. Romosozumab increases bone formation and decreases bone resorption.
Dr Geusens noted that approximately 30% of postmenopausal women in Europe and the United States have osteoporosis. One or more fragility fractures will be sustained by 40% of these women over their lifetime, most often in the hip, spine, and wrist. Concern is strongest over hip and vertebral fractures, with the latter associated with intense back pain and deformity.
Previous research has shown gains in trabecular and cortical compartments of the spine and hip regions with 1 year of monthly subcutaneous romosozumab injections. The FRAME investigators enrolled 7180 postmenopausal women (mean age, 71 years) with evidence of osteoporosis confirmed by abnormally low bone density scores in their spine, hip, and femoral neck, but no severe vertebral fracture. At baseline, the women had a mean bone mineral density T-score of –2.7 at the lumbar spine, –2.47 at the total hip, and –2.75 at the femoral neck. Approximately 20% of the women had a previous vertebral fracture, and 22% a previous nonvertebral fracture.
The FRAME patients were randomized 1:1 to monthly romosozumab (210 mg; n = 3589) or placebo (n = 3591). Initial FRAME results had already shown a reduced risk for new vertebral fractures compared with placebo, with benefits appearing quickly (Cosman F, et al. N Engl J Med. 2016;375:1532-1543). Of 16 vertebral fractures reported in the romosozumab group, only 2 occurred in the second 6 months of therapy.
Dr Geusens’ presentation at the EULAR meeting focused on the 119 women who developed back pain consistent with a vertebral fracture diagnosis. X-ray confirmations of suspected fractures were enabled by monthly study visits. Bone mineral density had increased in the romosozumab group by 13% more than in the placebo group at the lumbar spine, by 7% more at the total hip, and by 6% more at the femoral neck. Among this group, new or worsening vertebral fractures were diagnosed in 20 women. Of these, 3 occurred in the romosozumab group (0.1%) and 17 occurred in the placebo group (0.5%), with clinical vertebral fracture risk reduced by 83% for romosozumab versus placebo. Bone mineral density measurements revealed more severe osteoporosis in women with vertebral fractures at baseline, however.
Although Dr Geusens did not address adverse events, the earlier published FRAME results reported that romosozumab was generally well-tolerated. Rates of cardiovascular death were similar for both groups at 12 months with 17 deaths in the romosozumab group and 15 in the placebo group; each group had similar serious adverse rates of approximately 1%.
“These results support this new class of drug as a highly effective treatment for postmenopausal women with osteoporosis with established bone mineral density deficit who are at increased risk of fracture,” Dr Geusens concluded.