A new treatment for osteoporosis provides major improvements in bone density and more effective protection against fractures than the current standard treatment. These are the findings of a study, which is the first that compares the effect of two osteoporosis medicines on fractures.
“With the new treatment, we could offer significantly better protection against fractures and could thereby help many patients with severe osteoporosis,” says co-author of the study Mattias Lorentzon, professor of geriatrics at the Institute of Medicine, Sahlgrenska Academy, University of Gothenburg and senior physician at Sahlgrenska University Hospital.
Many patients with severe osteoporosis and a high risk of fractures often cannot regain their original bone strength. They continue to have fractures even with treatment according to current standards with alendronate in tablet form every week.
Alendronate increases bone density by slowing the breakdown of bone and thereby decreasing the risk of fractures by 20%-50%. Many people with osteoporosis, especially elderly women, nonetheless continue to suffer broken bones, sometimes just by falling from a standing position. The fractures lead to disability and suffering, and with hip and vertebral fractures, often premature death.
The current study included 4,093 women, of an average age of 74 years, with osteoporosis and previous fractures. They were randomly allocated to 12 months’ treatment with either alendronate or the new medication romosozumab, an antibody that blocks the substance sclerostin, which slows the new formation of bone. Treatment with romosozumab thereby leads to rapid new bone formation. After the first 12 months, all patients received alendronate for 12 months.
The risk of vertebral fracture in the course of the study proved to be 48% lower for those who received romosozumab compared with the group that received alendronate the whole time. The proportions suffering fractures in the two groups were 6.2% and 11.9%, respectively.
The risk of a clinical fracture, such as an arm or leg fracture, was 27% lower in the group that received romosozumab. Here, the proportions suffering fractures in the different groups were 9.7% and 13.0%, respectively.
The proportion of side effects and serious side effects was generally just as common in both of the treatment groups. However, it was observed that serious cardiovascular events, such as heart attack or stroke, occurred in 2.5% of the patients that received romosozumab compared with 1.9% in the group that received alendronate during the first 12 months of the study.
According to Lorentzon, the safety aspects of the new medication need to be studied further. However, an earlier study of nearly twice the size showed that romosozumab does not provide a greater risk of cardiovascular events compared with a placebo.
“With romosozumab in the treatment arsenal, we could prevent many fractures among the high-risk patients,” he concludes.
Background: Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption.
Methods: We enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture (nonvertebral and symptomatic vertebral fracture) at the time of the primary analysis (after clinical fractures had been confirmed in ≥330 patients). Secondary end points included the incidences of nonvertebral and hip fracture at the time of the primary analysis. Serious cardiovascular adverse events, osteonecrosis of the jaw, and atypical femoral fractures were adjudicated.
Results: Over a period of 24 months, a 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group (6.2% [127 of 2046 patients]) than in the alendronate-to-alendronate group (11.9% [243 of 2047 patients]) (P<0.001). Clinical fractures occurred in 198 of 2046 patients (9.7%) in the romosozumab-to-alendronate group versus 266 of 2047 patients (13.0%) in the alendronate-to-alendronate group, representing a 27% lower risk with romosozumab (P<0.001). The risk of nonvertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group (178 of 2046 patients [8.7%] vs. 217 of 2047 patients [10.6%]; P=0.04), and the risk of hip fracture was lower by 38% (41 of 2046 patients [2.0%] vs. 66 of 2047 patients [3.2%]; P=0.02). Overall adverse events and serious adverse events were balanced between the two groups. During year 1, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate (50 of 2040 patients [2.5%] vs. 38 of 2014 patients [1.9%]). During the open-label alendronate period, adjudicated events of osteonecrosis of the jaw (1 event each in the romosozumab-to-alendronate and alendronate-to-alendronate groups) and atypical femoral fracture (2 events and 4 events, respectively) were observed.
Conclusions: In postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone.
Kenneth G Saag, Jeffrey Petersen, Maria Luisa Brandi, Andrew C Karaplis, Mattias Lorentzon, Thierry Thomas, Judy Maddox, Michelle Fan, Paul D Meisner, Andreas Grauer