Does efficacy of denosumab (Prolia) decrease after 5 years of use?

From the Guidelines

There is no clear evidence of decreased efficacy after 5 years of using Prolia (denosumab), and long-term studies show that Prolia continues to be effective at increasing bone mineral density and reducing fracture risk beyond 5 years of treatment. The most recent and highest quality study, the ABCSG-18 trial, demonstrated that denosumab significantly decreased the risk of fractures in postmenopausal women with osteoporosis, with a significant decrease in fractures overall and for subgroups, including those with baseline low bone mineral density 1.

Key Points

• The American College of Physicians recommends treating osteoporotic women with pharmacologic therapy for 5 years, but this recommendation is based on low-quality evidence 1.
• Long-term use of denosumab has been shown to be effective in reducing fracture risk, with some studies demonstrating continued increases in bone mineral density and sustained fracture reduction for up to 10 years of continuous use.
• If Prolia is discontinued, there is a rapid reversal of its effects with accelerated bone loss and increased risk of multiple vertebral fractures, highlighting the importance of transitioning to another osteoporosis medication rather than simply discontinuing treatment.
• Regular monitoring with bone density tests every 1-2 years is recommended to assess ongoing effectiveness, and some patients may benefit from a drug holiday or switching to another medication after long-term use, based on individual fracture risk assessment.

Recommendations

• Denosumab should be continued beyond 5 years in patients who have shown a beneficial response to treatment and have a high risk of fracture.
• Patients stopping Prolia should transition to another osteoporosis medication rather than simply discontinuing treatment.
• Regular monitoring with bone density tests every 1-2 years is recommended to assess ongoing effectiveness.

From the Research

Efficacy of Denosumab (Prolia) After 5 Years of Use

• The efficacy of denosumab (Prolia) in treating postmenopausal osteoporosis has been evaluated in several studies 2, 3, 4.
• A study published in 2017 found that denosumab increased bone mineral density (BMD) in patients with postmenopausal osteoporosis, with a BMD increase of 4.2% at 12 months, 7.5% at 24 months, and 8.8% at 36 months in the lumbar spine 2.
• Another study published in 2018 found that denosumab reduced the risk of vertebral, nonvertebral, and hip fractures and increased BMD across skeletal sites, with benefits maintained over up to 10 years of therapy 3.
• However, a case report published in 2020 found that denosumab failure can occur due to escape from suppression of bone resorption, which may be under-reported in patients who do not respond to denosumab 5.
• A study published in 2016 compared the effect of transitioning from oral bisphosphonates to denosumab or zoledronic acid on BMD and bone turnover, and found that denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with zoledronic acid 6.

Factors Affecting Efficacy

• The efficacy of denosumab may be affected by factors such as patient compliance, bone turnover markers, and prior treatment with other osteoporosis therapies 2, 5, 6.
• A study published in 2014 found that denosumab was effective in increasing BMD and reducing markers of bone turnover in postmenopausal women with osteoporosis, regardless of prior treatment with other osteoporosis therapies 4.

Long-Term Use

• The long-term use of denosumab has been evaluated in several studies, with benefits maintained over up to 10 years of therapy 3, 4.
• However, the potential for multiple vertebral fractures to occur after discontinuation of denosumab requires consideration of subsequent management options 3.