Abaloparatide: How the FDA-Approved Osteoporosis Peptide Works

At a glance

What is abaloparatide?

Abaloparatide is a synthetic 34-amino acid peptide modeled on a signaling molecule your body already makes, called parathyroid hormone-related protein (PTHrP). Abaloparatide isn't a receptor itself; it instead binds to PTH1R, a G-protein–coupled receptor sitting on the surface of your bone-building cells. Once attached, it triggers a pathway that instructs those cells to create new bone. This can increase the density of bones, improving their strength and reducing the likelihood of bone fractures. It is given as a daily subcutaneous injection for postmenopausal women who are experiencing osteoporosis. It can also be prescribed for others, including men, who have either not responded well to or tolerated other osteoporosis medications.

How does abaloparatide work?

Bone is constantly being torn down (resorption) and rebuilt (formation). Abaloparatide ramps up the build-up faster than the tear-down so that new bone is created quicker than old bone is removed. This creates what's called an anabolic window, the stretch where bone formation outpaces bone resorption. Abaloparatide also influences the calcium and phosphate balance in the body, both of which are minerals that contribute to bone health. In trials, abaloparatide reduced the risk of major fractures; in the spine, the relative risk reduction for new fractures was 86%, and in nonvertebral fractures it was 43%. In addition to reducing fractures, abaloparatide increases bone mineral density, which measures the amount of calcium and other minerals in your bones to determine the bones’ strength and fracture risk. In a large trial abbreviated ACTIVE, it had a statistically significant impact on the hip, lower spine, and femoral neck (the bone that connects the femur to the hip). In comparison to the placebo, bone mineral density increased at each site as follows:

Strong results were seen as soon as six months. Abaloparatide is used for at maximum two years.

Is it FDA-approved?

Yes, abaloparatide has been FDA-approved since 2017 under the brand names Tymlos and Eladynos.

What is abaloparatide prescribed for?

Estrogen is one of the body’s natural brakes on bone breakdown. When estrogen levels fall during menopause, that brake comes off: bone resorption speeds up, outpaces formation, and many women lose bone density rapidly in the years right afterward, especially with the spine and hip. (These bones are highly load-bearing structures that are the easiest places to identify bone density.) Abaloparatide works directly against that imbalance. Rather than only slowing the accelerated breakdown (as many osteoporosis drugs do), it helps actively rebuilds bone, helping to recover some of what was lost and restore strength in the areas where postmenopausal bone loss does the most damage. Because abaloparatide actively builds new bone rather than just slowing bone loss, it makes it a heavier hitter than most osteoporosis drugs. For that reason, it’s generally reserved for people whose fracture risk is high enough to justify it, i.e. someone who has already broken a bone, whose bone-density scores are very low, or who has several risk factors. It's also approved for men with osteoporosis at high fracture risk, too, not just postmenopausal women. Doctors typically don’t prescribe it to people with a higher baseline risk of bone cancer, including Paget’s disease of bone, a history of bone cancer or radiation to the skeleton, or unexplained elevated alkaline phosphatase on bloodwork. It’s also generally avoided in people who already run high on blood calcium or who are prone to calcium-based kidney stones.

What are the side effects?

Tymlos lists the potential side effects as:

• Dizziness
• Nausea
• Headache
• Fast heartbeat
• Fatigue
• Vertigo
• Redness, swelling, and/or bruising at injection site
• Joint and/or bone pain
• Abdominal bloating or pain
• Diarrhea
• Nausea Serious side effects can include:
• Increased blood calcium (hypercalcemia)
• Increased urine calcium (hypercalciuria), which may cause kidney stones

How does abaloparatide compare to teriparatide?

Teriparatide (Forteo) was considered first-in-class as it was FDA-approved in 2002, 15 years before abaloparatide. Both are daily injections, anabolic drugs that build new bone through the same receptor (PTH1R), and are capped at two years of lifetime use. However, teriparatide is a fragment of parathyroid hormone (PTH) itself while abaloparatide is synthetically modeled on PTHrP. That difference is how abaloparatide is a more bone-building, less bone-dissolving drug There is no study that has a direct comparison between the two drugs, but rather trials compare them to placebo groups where teriparatide serves as the active control group. The best evidence comes from the ACTIVE trial, which included both drugs:

• Spine fractures were roughly comparable: Abaloparatide cut new vertebral fractures by 86% and teriparatide by 80% versus placebo. Neither was shown to beat the other here.
• Nonvertebral fractures: Abaloparatide showed a statistically significant 43% reduction, while teriparatide’s 28% reduction didn’t reach significance in this trial.
• Major osteoporotic fractures: Abaloparatide beat teriparatide significantly with a 55% lower risk.
• Bone density: There were similar increases at the spine, but abaloparatide produced significantly greater increases at the hip and femoral neck.
• Hypercalcemia was less common with abaloparatide (3.4%) than with teriparatide (6.4%).

Evidence strength

FDA approved: It is approved by the FDA for osteoporosis in postmenopausal women and men at high fracture risk, backed by the pivotal ACTIVE double-blind, placebo-controlled trial.

Sources: the pivotal ACTIVE trial in JAMA; FDA prescribing information for Tymlos (abaloparatide); and background references on PTHrP and PTH1R signaling. This document is educational and does not constitute medical advice.