Abaloparatide

What is abaloparatide?

Abaloparatide is a synthetic peptide made up of 34 amino acids. It is modeled on the body’s own signaling molecule, parathyroid hormone-related protein (PTHrP) 1. Abaloparatide is not itself a receptor: it binds to PTH1R, a G protein-coupled receptor 2 on the surface of bone-forming cells. Source Source

Once it binds, it activates a signaling pathway that tells these cells to make new bone. This can increase bone density, improve bone strength and reduce the likelihood of fractures.

Postmenopausal women receive it for osteoporosis as a daily injection under the skin 1. It may also be prescribed to other people, including men, when other osteoporosis medicines do not work well enough or cannot be tolerated. Source

How does abaloparatide work?

Bone is constantly being broken down, a process called resorption, and rebuilt, a process called formation 3. Abaloparatide stimulates formation more than resorption. This creates what is known as an anabolic window: a period in which more bone is formed than broken down. Source

Abaloparatide also affects the body’s balance of calcium and phosphate, two minerals that contribute to bone health. In studies, it reduced the risk of serious fractures: the relative reduction in the risk of new spinal fractures was 86% 2, and the reduction for nonvertebral fractures was 43% 1. Source Source

Abaloparatide reduces fracture risk and increases bone mineral density 4. Bone mineral density describes the amount of calcium and other minerals in bone and is used to assess bone strength and fracture risk. In the large ACTIVE trial 5, bone density increased by statistically significant amounts at the hip, lower spine and femoral neck. The femoral neck connects the shaft of the thighbone to its rounded head. Compared with placebo, the increases were as follows: Source Source

Measurement site	Increase in bone mineral density compared with placebo
Hip	4.25%
Lower spine	10.37%
Femoral neck	4.01%

Clear effects were apparent after six months. Abaloparatide is used for a maximum of 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 slows bone breakdown. As estrogen levels fall during menopause, breakdown speeds up and can outpace formation. Many women lose bone density rapidly in the following years, particularly at the spine and hip. These weight-bearing areas are useful sites for measuring bone density. Abaloparatide counteracts the imbalance between bone breakdown and formation.

Many osteoporosis medicines mainly slow the breakdown of existing bone. Abaloparatide promotes the formation of new bone. It can therefore help replace some of what has been lost and strengthen bone in areas where breakdown after menopause is particularly pronounced.

Because it stimulates bone formation, abaloparatide has a substantial effect on bone remodeling. It is usually reserved for people at high risk of fractures: those who have already had a fracture, have very low bone density or have several risk factors. It is also approved for men with osteoporosis 6 who are at high risk of fractures, as well as for postmenopausal women. Source

Doctors generally do not prescribe it to people with a higher underlying risk of bone cancer. This includes people with Paget’s disease of bone 6, a history of bone cancer or radiation treatment to the skeleton, or unexplained elevations in blood alkaline phosphatase. It is also generally avoided in people who already have high blood calcium or are prone to calcium-based kidney stones. Source

What side effects are possible?

The manufacturer’s information for Tymlos 7 lists the following possible side effects: Source

• Dizziness
• Nausea
• Headache
• A fast heartbeat
• Fatigue
• Vertigo, or a spinning sensation
• Redness, swelling and/or bruising at the injection site
• Joint and/or bone pain
• Bloating or abdominal pain
• Diarrhea
• Nausea

Serious side effects may include:

• Elevated calcium in the blood, or hypercalcemia
• Elevated calcium in the urine, or hypercalciuria, which can lead to kidney stones

How does abaloparatide differ from teriparatide?

Teriparatide (Forteo) was considered the first medicine in its class 8: it received FDA approval in 2002, 15 years before abaloparatide. Both medicines are injected daily and promote bone formation through the same receptor, PTH1R. Their use is limited to a total of two years over a person’s lifetime. Teriparatide, however, is a fragment of parathyroid hormone (PTH) itself, whereas abaloparatide is a synthetic molecule modeled on PTHrP. This difference explains why abaloparatide stimulates bone formation more strongly and bone resorption less strongly. Source

There has not been a study designed specifically as a direct comparison of the two medicines. Instead, they were studied against placebo, with teriparatide serving as an active control. The most informative data come from the ACTIVE trial, which included both medicines:

• Spinal fractures: the findings were broadly similar. Abaloparatide reduced new vertebral fractures by 86% and teriparatide by 80% compared with placebo. Neither medicine was shown to be superior to the other on this measure.
• Nonvertebral fractures: abaloparatide produced a statistically significant reduction of 43%. The 28% reduction with teriparatide did not reach statistical significance in this study.
• Major osteoporotic fractures: the risk was a statistically significant 55% lower with abaloparatide than with teriparatide.
• Bone density: increases at the spine were similar, but abaloparatide produced significantly greater increases at the hip and femoral neck.
• Hypercalcemia occurred less often with abaloparatide (3.4%) than with teriparatide (6.4%).

Sources and supporting evidence

Sources: the pivotal ACTIVE trial in JAMA; FDA prescribing information for Tymlos (abaloparatide); and background references on PTHrP and PTH1R signaling.