Continuous treatment of osteoporosis with denosumab provides long-term benefit
Denosumab continuously increases bone mineral density (BMD) at the spine and hip over 10 years, and long-term treatment is associated with reduced incidence of both vertebral and nonvertebral fractures, according to a presentation at the 6th Asia-Pacific Osteoporosis Meeting (IOF Regionals 2016) held in Singapore.
“The goal of [osteoporosis] therapy is to restore bone mass and bone quality in all aspects, whatever time that takes,” said Professor Serge Ferrari of Service of Bone Diseases at Geneva University Hospital in Geneva, Switzerland, suggesting a T-score target of -2 to -1.5 to minimize fracture risk in the long term.
Being highlighted was the FREEDOM* extension trial, a multicentre open-label single-arm study which followed participants who had completed the initial 3 years of the FREEDOM trial for another 4 years. The extension study included 4,074 postmenopausal women with osteoporosis randomized to either subcutaneous denosumab 60 mg Q6M or placebo in the initial 3 years, who were continued (ie, long-term group) or crossed-over, respectively, to receive denosumab from years 4–7 during the extension period. [Osteoporos Int 2015;26:2763-2771]
Compared with the initial 3 years of denosumab treatment, nonvertebral fracture rate was 25 percent lower at year 4 in the long-term group (1.98 vs 1.48, rate ratio [RR], 0.75; p=0.127). Similarly, a significant reduction of 21 percent in fracture rate was observed in the cross-over group at year 4 of treatment (2.37 vs 1.2, RR, 0.79; p=0.0046).
Furthermore, the overall nonvertebral fracture rate was decreased by 21 percent during years 4–7 compared with the initial 3 years of denosumab treatment in the long-term group (1.98 vs 1.54, RR, 0.79; p=0.046).
Collectively, the study showed that treatment with denosumab beyond 3 years was associated with a further reduced risk of nonvertebral fracture which persisted throughout 7 years of continuous treatment, according to Ferrari.
Also, the extent of reduction in nonvertebral fracture risk achieved with denosumab appeared to be dependent on the femoral neck BMD achieved during the initial 3-year therapy, he added. “Fracture rate reduction in year 4 was most prominent in subjects with persisting low hip BMD.”
Discussing about the 10-year data with denosumab, Ferrari pointed out that denosumab persistently increased lumbar spine BMD and decreased new vertebral fracture incidence throughout the 10-year extension period of the FREEDOM study. [ASBMR** 2015, abstract 1157]
“Denosumab continuously increases BMD at the spine and hip over 10 years, resulting in a majority of subjects achieving a nonosteoporotic T-score,” he said.
“As you treat longer, you need to balance the risk and benefit [of a therapy],” said Ferrari, noting that there was no cumulative risk of infections or other adverse events with denosumab treatment over 8 years as shown in the phase II study of the drug. [Osteoporos Int 2013;24:227-235]