Evenity vs Prolia for Osteoporosis

Osteoporosis is a progressive condition that causes bones to become weak and more likely to break. In the US, about 10 million people have osteoporosis, and another 44 million have osteopenia (low bone density), putting them at greater risk for fractures.

Affected individuals usually rely on medications to slow bone loss and reduce fracture risk. Among the most commonly prescribed injectable treatments are Evenity (romosozumab) and Prolia (denosumab).

Though both are effective, they work differently and come with unique considerations. This comprehensive guide explains the differences between Evenity and Prolia.

Approved Indications of Evenity vs. Prolia

Although both Evenity and Prolia are prescribed for osteoporosis, they differ in their FDA-approved uses.

Evenity is only approved for women who are at high risk of fracture after menopause. Regulatory bodies in the US have yet to extend approval for male use or secondary causes of bone loss, such as medication-induced osteoporosis.

Prolia has a broader range of indications, including use in both sexes and for patients who experience bone loss as a side effect of other treatments.

It’s FDA-approved for:

• • Postmenopausal women with osteoporosis
  • Men with osteoporosis
  • Glucocorticoid-induced osteoporosis in men and women
  • Bone loss in men receiving androgen-deprivation therapy for prostate cancer
  • Bone loss in women receiving aromatase inhibitors for breast cancer

Because it’s approved for a wider range of patients, Prolia may be considered in more treatment plans, depending on individual needs.

Effectiveness of Evenity vs. Prolia

There is no large-scale, direct head-to-head clinical trial comparing Evenity and Prolia. However, analysis of existing trials suggests that Evenity may be more effective in increasing bone mineral density (BMD). At the same time, Prolia has more long-term data supporting fracture prevention with ongoing use.

Reducing Fractures

Findings from the FRAME Study (in postmenopausal women) showed that after 1 year on Evenity, there were:

• • 73% fewer new spinal fractures (also called vertebral fractures)
  • 36% fewer clinical fractures (any fractures that cause symptoms and are brought to medical attention, including spine, hip, wrist, shoulder, rib, or other bones)
  • 25% fewer nonvertebral fractures (fractures that occur outside the spine, like the hip, wrist, pelvis, upper arm, leg, or rib fractures)

In the ARCH study, those who started with Evenity had:

• • 48% fewer spinal fractures
  • 27% fewer clinical fractures
  • 19% fewer nonvertebral fractures

Prolia also has strong data behind it. In the FREEDOM trial, Prolia was used for three years and led to:

• • 68% fewer spinal fractures
  • 40% fewer hip fractures
  • 20% fewer nonvertebral fractures

In a comparative clinical analysis, experts compared Evenity alone versus vertebroplasty (a surgical procedure) combined with Prolia in treating patients with osteoporotic vertebral compression fractures (OVCF).

At the end of the study, fewer major osteoporotic fractures occurred in the Evenity group (7.1% vs. 25.0% in the vertebroplasty group). This shows Evenity’s potential in fracture prevention. Evenity patients also had better pain scores at 12 months, which suggests that it may offer longer-lasting pain relief compared to surgery.

Bone Mineral Density (BMD) Gains

In one study, researchers used a database of real-world patients being treated with Evenity or Prolia for osteoporosis. After 12 months:

• • Evenity increased spine bone density by 12.5%
  • Prolia increased spine bone density by 7.2%

Evenity also led to greater improvements in the hip and femoral neck compared to Prolia.

A systematic review and meta-analysis of six studies had similar findings. After 3 months, Evenity led to greater improvements in spine bone density. Bone metabolism markers also improved more with Evenity.

After 6 to 12 months, Evenity consistently outperformed Prolia in improving:

• • Bone density in the spine, hip, and femoral neck
  • Bone turnover markers (higher bone formation, lower bone breakdown)

In the comparative clinical analysis mentioned earlier, spine BMD increased by 28.8% in the Evenity group and 15.3% in the vertebroplasty + Prolia group. At the hip, Evenity also showed a trend toward better results.

Researchers also analyzed 174 Japanese men to compare the effectiveness of Evenity and Prolia over a 12-month period, as Evenity is approved in Japan for use in men. Results showed that Evenity increased spine bone density by 13%, while Prolia increased it by only 4.5%. For the hip and femoral neck, Evenity also showed higher gains.

How Evenity and Prolia Work

Evenity (romosozumab-aqqg) is considered an anabolic agent, which means it actively stimulates new bone growth. On the other hand, Prolia (denosumab) is an antiresorptive agent, which prevents further loss of bone but doesn’t build new bone as directly as Evenity.

Because of this, Evenity is usually prescribed earlier in a treatment plan to quickly build bone mass, while Prolia may be used longer term to help maintain that density.

Evenity blocks a protein called sclerostin. Sclerostin inhibits bone formation, so by blocking it, Evenity promotes the growth of new bone while also decreasing how quickly bone is lost. This combined effect makes Evenity unique among osteoporosis drugs.

Meanwhile, Prolia blocks a protein called RANK ligand, which is involved in the formation and activity of osteoclasts. These are cells that break down bone tissue. By reducing osteoclast activity, Prolia helps slow down bone loss and strengthens existing bone.

Side Effects and Safety Concerns

Side effect profiles of Evenity and Prolia overlap in some areas but differ in others. According to clinical trials and FDA labeling, both can cause joint pain, muscle symptoms, and injection site reactions. They also carry a risk of hypocalcemia or low calcium levels.

However, Prolia is also associated with side effects like high cholesterol, bladder infection, and pancreatitis, especially in postmenopausal women with osteoporosis.

One of the major differentiators between Evenity and Prolia is cardiovascular safety. Evenity showed a slightly increased risk of heart attack, stroke, and cardiovascular death in clinical trials, especially in high-risk individuals.

Prolia has not been linked to an increased cardiovascular risk in most studies. As a result, doctors may avoid prescribing Evenity to patients with a history of stroke, heart attack, or other vascular conditions.

Dosing and Administration of Evenity vs. Prolia

Evenity requires two injections, each containing 105 mg, each month for a year. This is because the full dose, 210 mg total, is too large to be safely or comfortably injected in a single shot. The injections are given one after the other, usually in different sites (e.g., one in each upper arm, thigh, or abdomen).

After completing Evenity, patients often transition to another osteoporosis medication, such as Prolia or a bisphosphonate (Fosamax, Actonel, Boniva, Reclast).

Prolia is administered every six months (60 mg) and can be continued indefinitely under medical supervision.

Dose Adjustments of Evenity vs. Prolia in Specific Populations

Here’s a comparison of dose adjustment requirements and safety considerations for Evenity and Prolia in special populations:

Osteoporosis Management During Hemodialysis

A 12-month observational study looked into how the drugs (Evenity and Prolia) perform in real clinical settings, particularly on patients undergoing hemodialysis (HD) who also had osteoporosis. Spine BMD increased 14.6% with Evenity vs. 6.3% with Prolia.

Both groups had one fracture each. Someone on Evenity had a spine fracture, and someone on Prolia had a hip fracture. This suggests a similar safety level in terms of fracture risk. More importantly, calcium levels stayed normal and stable in both groups.

Switching Between Evenity and Prolia

Switching from Evenity to Prolia is common and recommended in most cases. Here’s the typical sequence:

• • Start with Evenity for 12 months
  • Transition to Prolia one month after the last monthly dose of Evenity

The FRAME Extension study evaluated the effectiveness of Evenity, followed by Prolia, in over 7,000 postmenopausal women with osteoporosis. Results after 36 months showed that fracture risk was lower in the Evenity-to-Prolia group than in the placebo-to-Prolia group:

• • 66% fewer new spinal fractures
  • 27% fewer clinical fractures
  • 21% fewer nonvertebral fractures

BMD continued to improve in both groups during the 2 years of Prolia treatment, but those who started with Evenity kept their advantage from the first year. Side effects were also similar between the two groups.

However, switching from Prolia to Evenity may not work well. Some patients were seen to have major osteoporotic fractures (MOFs) or signs of increased bone loss after making the switch.

Costs and Insurance Coverage

The list price of Evenity shots for osteoporosis is $2,628.92 per month, but retail prices in the US can climb as high as $3,200, depending on the pharmacy. Since Evenity is taken once a month for 12 months, the total annual cost can range from $31,547 to $38,400 without insurance.

In comparison, Prolia is significantly cheaper. The list price for Prolia is $1,875.43 per injection. These prices can vary depending on your insurance plan, location, and pharmacy. Medicare Part B often covers both drugs.

Want to Save on Evenity?

You can order Evenity from Pharma Giant, a trusted Canadian pharmacy network that ships to the US. Through Pharma Giant, Evenity is available for only $1,030 per month.

You can save even more by purchasing a 3-month supply for just $3,030. Pharma Giant supplies the same FDA-approved Evenity, but at a much lower cost, thanks to Canada’s national drug pricing system, which helps keep medications affordable.

Who Might Benefit Most?

Here’s a summary of who may benefit more from each option.

Evenity

Prolia

Summary

Evenity and Prolia are two effective injectable treatments for osteoporosis, each with unique advantages and limitations. Evenity builds bone quickly and is used for one year, while Prolia helps maintain bone strength over the long term. The right option for you depends on your medical history, bone density status, and treatment goals.

Discuss these options thoroughly with your doctor and make sure to have a clear plan in place for transitions, monitoring, and long-term care. Bone health is a lifelong journey, and these medications, when used correctly under medical supervision, can make a significant difference.

Frequently Asked Questions