From the Guidelines
Prolia (denosumab) is a highly effective treatment for osteoporosis, with the strongest evidence of benefit demonstrated in reducing the risk of fracture, as shown in a 2019 study published in the Journal of Clinical Oncology 1. The medication is typically administered as a 60mg subcutaneous injection every six months, making it convenient for long-term treatment.
- Prolia works by inhibiting RANK ligand, a protein essential for osteoclast formation and function, thereby decreasing bone resorption and increasing bone density.
- The medication is particularly valuable for patients who cannot tolerate or haven't responded to other osteoporosis treatments like bisphosphonates.
- Side effects are generally mild but can include back pain, extremity pain, and hypocalcemia.
- Patients should take calcium and vitamin D supplements while on Prolia to prevent low calcium levels.
- It's essential to maintain treatment without interruption, as discontinuation can lead to rapid bone loss and increased fracture risk, with the European Calcified Tissue Society suggesting the use of a bisphosphonate to reduce this risk upon stopping denosumab 1.
- Regular bone density scans are recommended to monitor treatment effectiveness. The American College of Physicians also recommends offering pharmacologic treatment with denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis, based on high-quality evidence from a 2017 study published in the Annals of Internal Medicine 1.
From the FDA Drug Label
The primary efficacy variable was the incidence of new morphometric (radiologically-diagnosed) vertebral fractures at 3 years. Prolia significantly reduced the incidence of new morphometric vertebral fractures at 1,2, and 3 years (p < 0.0001), as shown in Table 3. The incidence of new vertebral fractures at year 3 was 7.2% in the placebo-treated women compared to 2.3% for the Prolia-treated women. The absolute risk reduction was 4.8% and relative risk reduction was 68% for new morphometric vertebral fractures at year 3.
The efficacy of Prolia (Denosumab) is as follows:
- Reduction in vertebral fractures: 68% relative risk reduction and 4.8% absolute risk reduction at 3 years.
- Reduction in hip fractures: 40% relative risk reduction and 0.3% absolute risk reduction at 3 years.
- Reduction in nonvertebral fractures: 20% relative risk reduction and 1.5% absolute risk reduction at 3 years.
- Increase in bone mineral density (BMD): 8.8% at the lumbar spine, 6.4% at the total hip, and 5.2% at the femoral neck at 3 years 2.
From the Research
Efficacy of Prolia (Denosumab)
- Denosumab has been shown to reduce the risk of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis 3, 4, 5.
- The drug increases bone mineral density (BMD) at all skeletal sites evaluated, including the lumbar spine and total hip 3, 5.
- Denosumab has been found to be more effective in improving BMD than bisphosphonates, including in women switched from a bisphosphonate regimen 3, 4, 5.
- The benefits of denosumab treatment are generally evident after the first dose and are maintained during up to 10 years of treatment 4.
Subgroup Analysis
- Denosumab decreases the risk of new vertebral fractures in all subgroups analyzed, including women with different ages, BMD, and fracture history 6.
- The effect of denosumab on nonvertebral fracture risk differs by femoral neck BMD, body mass index (BMI), and prevalent vertebral fracture at baseline 6.
Safety and Tolerability
- Denosumab is generally well tolerated, with a safety profile consistent with that observed during the initial 3-year FREEDOM trial 3, 4.
- Initial safety concerns included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures, but further study and experience provide reassurance on these issues 7.
- Anecdotal reports have raised concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab 4, 7.