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A Bone to Pick With Osteoporosis

by | Sep 6, 2023 | Biotech for Non-Scientist


In the ever-changing field of osteoporosis treatments, Amgen’s Evenity and Radius Health’s Tymlos (Abaloparatide) stand out as key players. Evenity, an antibody drug by Amgen, has received FDA approval and has proven effective in rebuilding bone. On the other hand, Radius Health’s Abaloparatide, a peptide analog of human parathyroid-related protein, received FDA approval in 2022 specifically for men with osteoporosis.

Osteoporosis is the loss of bone density which causes bones to become weak, brittle, and easily broken. In healthy people, bone is constantly being broken down and replaced. Osteoporosis occurs when a bone is broken down more quickly than it is replaced. As the disease progresses, patients become more vulnerable to broken bones, especially in the hip, spine, and wrist. In advanced cases, even minor falls or bumps can result in a fracture, leading to loss of mobility.

According to the Bone Health and Osteoporosis Foundation, osteoporosis-related fractures number as many as two million per year in the US, with related costs at $19 billion. These numbers are expected to climb to three million and $25.3 billion, respectively, by 2025. Let’s break down how bone loss occurs, which therapies are

currently on the market, and which ones in the pipeline are threatening to become the new gold standard for osteoporosis care.


Bone formation and maintenance is a complex process that relies on many different interacting factors but is driven by two specific cell types: osteoblasts, which lay down bone tissue, and osteoclasts, which degrade bone tissue. This process may be activated when bone remodeling is required, such as in response to a fracture. Osteoclasts break down the damaged bone tissue by secreting an acidic substance in a process known as bone resorption, and then osteoblasts produce new tissue for bone formation. During childhood, formation exceeds resorption; as people age, resorption begins to exceed formation.

Other factors that influence bone formation and maintenance include calcium, vitamin D, the hormone estrogen, and weight-bearing exercise. Calcium is the mineral that provides bone with its hardness and strength. Because calcium plays a role in other critical metabolic processes like muscle contraction, diets that are inadequate in calcium may trigger the activation of bone resorption to release these vital mineral supplies into the bloodstream. Making sure that we absorb the mineral from the food we eat is necessary to keep up with demand, and vitamin D is essential to the calcium absorption process.

Weight-bearing exercises such as walking, jogging, or weight-lifting help to build and maintain bone mass. When stress is put on bones from weight-bearing exercise, they respond by activating osteoblasts to withstand the stress better, ultimately increasing bone density.

It’s long been known that estrogen protects women from bone loss. In the past decade, researchers at the University of Buffalo pinpointed the reason why: estrogen protects osteoblasts by inhibiting an enzyme that would normally trigger apoptosis— programmed cell death—in the osteoblast cells. This is why post-menopausal women have the highest rates of osteoporosis.


The most common treatment for osteoporosis today is a bisphosphonate, with the most widely prescribed drug being Fosamax (Merck; Kenilworth, NJ). Bisphosphonate drugs activate apoptosis (cell suicide) in osteoclasts and have been clinically shown to decrease fractures of the wrist, spine, and hip of at-risk post-menopausal women. However, these bone-preserving drugs may have some unpleasant gastrointestinal side effects, and their long-term use is associated with the development of low-impact femoral fractures. Thus the race is still on to find new osteoporosis drugs.


Forteo (Eli Lilly, Indianapolis, IN) is another popular treatment for osteoporosis. It is a recombinant version of the parathyroid hormone (PTH). While chronically high levels of the parathyroid hormone will activate osteoclasts, a once-daily injection of PTH can activate osteoblasts more than osteoclasts, thereby increasing bone growth.

Abaloparatide, by Waltham, MA startup Radius Health, is a peptide analog of human parathyroid-related protein. It is a naturally occurring peptide hormone that has a similar effect as the parathyroid hormone. Approved in 2022 by FDA for men with osteoporosis, Tymlos (abaloparatide) is as effective at preventing vertebral fractures as Forteo, and more effective at preventing other types of fractures.. Like Forteo, abaloparatide is an anabolic, or bone-growing, treatment. Radius Health is also currently conducting Phase III clinical trials of their Abaloparatide-TD for post-menopausal women with osteoporosis.


Another FDA-approved drug for osteoporosis is Amgen’s (Thousand Oaks, CA) Prolia. Prolia is a monoclonal antibody that works by inhibiting RANKL, a protein on the surface of osteoclasts. By impeding RANKL, osteoclast activation is diminished.

The FDA approved Evenity (romosozumab), an antibody osteoporosis drug developed by Amgen following positive Phase III results. Romosozumab works by inhibiting a protein called sclerostin, which hampers bone formation by osteoblasts. By suppressing the inhibitor, the drug appears to make bone-producing osteoblasts more active. A second company, OsteoGeneX (Kansas City, KS), is also developing a small molecule inhibitor of sclerostin. Sclerostin inhibitors are bone-building agents.

As the population ages, osteoporosis will become an even more prevalent problem. These new bone-strengthening drugs provide hope for good health and mobility for at-risk older adults.


The race for effective treatments is intensifying as the aging population faces an increasing risk of osteoporosis and its devastating fractures. From traditional bisphosphonates to groundbreaking therapies like Amgen’s Evenity and Radius Health’s abaloparatide, the medical community is on the cusp of a new osteoporosis-care era. These emerging treatments offer hope and a more comprehensive approach to bone health, aiming to slow bone loss and stimulate new bone formation. With millions of lives and billions of dollars at stake, the urgency for innovative, practical solutions has never been greater.


1. What is osteoporosis?

Osteoporosis is a condition characterized by weakened bones that are prone to fractures. It occurs when the creation of new bone doesn’t keep up with the removal of old bone, leading to decreased bone density.

2. How do current osteoporosis drugs work?

The most commonly prescribed osteoporosis drugs are bisphosphonates like Fosamax. These drugs work by inhibiting the action of osteoclasts, the cells responsible for breaking down bone tissue, thereby slowing bone loss.

3. What are the side effects of bisphosphonates?

Common side effects include gastrointestinal issues, and long-term use has been associated with low-impact femoral fractures.

4. What are the new drugs in the pipeline?

Newer drugs like Evenity by Amgen and abaloparatide by Radius Health aim to not only slow down bone loss but also promote bone formation. These drugs are showing promise in clinical trials and have received FDA approval for specific uses.

5. How do these new drugs differ from bisphosphonates?

Unlike bisphosphonates, which only slow down bone loss, these new therapies aim to stimulate the formation of new bone by activating osteoblasts, the cells responsible for laying down new bone tissue.

6. Why is there a need for new osteoporosis drugs?

The current treatments have limitations, including side effects and less effectiveness in promoting new bone growth. With the aging population and the rising incidence of osteoporosis, there is an urgent need for more comprehensive treatments.

7. What role do lifestyle factors play in osteoporosis management?

Lifestyle factors like adequate calcium and vitamin D intake, as well as weight-bearing exercises, can play a significant role in managing osteoporosis. These factors can help in the formation and maintenance of healthy bone tissue.

8. What is the future of osteoporosis treatment?

The future is promising, with several new drugs in the pipeline that could potentially revolutionize osteoporosis care. These drugs aim to provide a more comprehensive approach to managing the disease, from slowing bone loss to promoting new bone growth.

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Author: Emily Burke, PhD
Editor: Sarah Van Tiems, MS
Scientific Review: Tahir Hayat, MS


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