What is the efficacy of Prolia (denosumab) in treating osteoporosis?

From the Guidelines

Prolia (denosumab) is a highly effective treatment for osteoporosis, reducing fracture risk by 40-70% depending on the fracture type, as shown in the most recent study from 2024 1. The medication works by inhibiting bone breakdown, which increases bone mineral density by approximately 8-9% in the spine and 6% in the hip over three years. The medication is administered as a 60 mg subcutaneous injection once every six months, making it convenient for long-term management. Most patients see measurable improvements in bone density within the first year of treatment. Prolia is particularly effective for postmenopausal women and men with osteoporosis who are at high risk for fractures or who cannot tolerate other osteoporosis medications. Some key points to consider when prescribing Prolia include:

• The importance of taking calcium and vitamin D supplements to maintain proper calcium levels and maximize the medication's effectiveness
• The potential side effects, such as low calcium levels, skin infections, and bone, joint, or muscle pain
• The need for consistent treatment, as Prolia's effects wear off quickly if discontinued
• The recommendation to use Prolia as a second-line pharmacologic treatment for postmenopausal females diagnosed with primary osteoporosis who have contraindications to bisphosphonates, as suggested by the American College of Physicians in 2023 1. Overall, Prolia is a valuable treatment option for patients with osteoporosis, and its efficacy and safety profile make it a recommended choice for those at high risk of fractures. Key benefits of Prolia include:
• Reduced fracture risk
• Increased bone mineral density
• Convenient administration schedule
• Effective for postmenopausal women and men with osteoporosis
• Can be used as a second-line treatment for those with contraindications to bisphosphonates. It's essential to weigh the benefits and harms of Prolia, as well as patient values and preferences, when making treatment decisions, as outlined in the American College of Physicians' living clinical guideline from 2023 1.

From the FDA Drug Label

The efficacy and safety of Prolia in the treatment of postmenopausal osteoporosis was demonstrated in a 3-year, randomized, double-blind, placebo-controlled trial. 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 incidence of hip fracture was 1.2% for placebo-treated women compared to 0.7% for Prolia-treated women at year 3. The age-adjusted absolute risk reduction of hip fractures was 0.3% with a relative risk reduction of 40% at 3 years (p = 0.04). Treatment with Prolia resulted in a significant reduction in the incidence of nonvertebral fractures.

The efficacy of Prolia (denosumab) in treating osteoporosis is significant, with a:

• 68% relative risk reduction in new morphometric vertebral fractures at 3 years
• 40% relative risk reduction in hip fractures at 3 years
• significant reduction in nonvertebral fractures Prolia is effective in reducing the risk of fractures in postmenopausal women with osteoporosis, regardless of age, baseline rate of bone turnover, baseline BMD, baseline history of fracture, or prior use of a drug for osteoporosis 2.

From the Research

Efficacy of Prolia (Denosumab) in Treating Osteoporosis

• Denosumab has been shown to be effective in reducing the risk of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis 3, 4, 5, 6.
• The drug has also been found to increase bone mineral density (BMD) at all skeletal sites evaluated, including the lumbar spine and total hip 3, 4, 5, 6.
• Denosumab has been compared to bisphosphonates in several studies, with results showing that it can increase BMD more than bisphosphonates in some cases 3, 4, 5, 6, 7.
• However, a systematic review and meta-analysis found that denosumab did not significantly reduce the risk of fracture compared to bisphosphonates in patients with osteoporosis who had not previously received bisphosphonate treatment 7.

Comparison to Other Osteoporosis Treatments

• Denosumab has been found to be more effective than bisphosphonates in improving BMD in some studies 3, 4, 5, 6, 7.
• Teriparatide has been shown to be superior to bisphosphonates in decreasing the risk of fracture in patients with osteoporosis, while denosumab did not show a significant benefit in reducing fracture risk compared to bisphosphonates 7.
• Both teriparatide and denosumab have been found to increase BMD at the femoral neck, total hip, and lumbar spine compared to bisphosphonates 7.

Safety and Tolerability

• Denosumab has been generally well tolerated in clinical trials, with a safety profile consistent with that observed during the initial 3-year FREEDOM trial 3, 4.
• However, an increased risk of multiple vertebral fractures has been observed after discontinuation of denosumab 4.
• Denosumab has not been found to increase the incidence of adverse events compared to bisphosphonates 7.