Cancer drug CADD522 shows bone-building and metabolic benefits in post-menopausal osteoporosis research

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Researchers at the University of East Anglia have found that CADD522, a RUNX2-targeting cancer compound, increased bone volume, preserved microarchitecture and reduced body fat in a post-menopausal mouse model.

An experimental drug originally developed to fight cancer could offer a new approach to treating osteoporosis after the menopause, according to research from the University of East Anglia (UEA).

The compound, CADD522, was designed to block RUNX2, a protein involved in the growth and spread of several cancers. However, researchers found that targeting the protein also appeared to benefit bone health and metabolism in post-menopausal mice.

After eight weeks of treatment, the mice had greater bone volume and better preservation of the delicate honeycomb-like structures inside bones that help them withstand stress. The animals also weighed less and had less body fat than untreated mice despite eating the same amount of food.

“We found that a drug originally developed to stop cancer could help millions of women facing the twin challenge of fragile bones and midlife weight gain. We hope our work could lead to a new generation of osteoporosis treatments that tackle bone loss while also addressing some of the wider metabolic consequences of menopause.”

Dr Darrell Green, Lead Researcher at UEA’s Norwich Medical School.

Why does this matter for drug discovery?

Bone is constantly remodelled, with cells responsible for building new bone working alongside cells that break old bone down. Menopause can disrupt this balance, accelerating bone loss and increasing fracture risk.

Many existing osteoporosis treatments work by slowing bone breakdown. While this can protect against fractures, researchers are also looking for ways to actively stimulate new bone formation – but CADD522 could offer a different route.

Researchers used mice that had undergone surgery to mimic the hormonal changes associated with menopause, with treatment increasing bone volume and preserving the internal architecture that contributes to bone strength.

Blood tests suggested CADD522 stimulated new bone growth without interfering with the body’s normal process of breaking down and rebuilding bone.

“This is particularly important because many existing osteoporosis drugs work by suppressing bone loss, which can sometimes lead to complications when used for long periods,” said Dr Green.

For early drug discovery, the distinction is important. Rather than simply slowing the loss of existing bone, a treatment that promotes bone formation could potentially complement or provide an alternative to approaches that focus on preventing bone breakdown.

Explainer: How does osteoporosis develop after menopause?

Bone is living tissue. Throughout life, old bone is broken down and replaced with new bone in a process called bone remodelling.

Hormones matter. Oestrogen helps regulate this process. When oestrogen levels fall during and after menopause, bone breakdown can accelerate.

Bones become weaker. If bone is lost faster than it is replaced, the skeleton becomes less dense and its internal structure can deteriorate.

Fracture risk increases. Osteoporosis can leave bones more vulnerable to fractures, particularly in the hip, spine and wrist.

Why CADD522 is interesting: Rather than focusing solely on stopping bone loss, the research suggests CADD522 may stimulate the formation of new bone while also influencing changes in fat metabolism.

An unexpected effect on body fat

The researchers were surprised to find that CADD522 appeared to affect metabolism as well as bone.

“The mice receiving CADD522 weighed less than their untreated counterparts despite eating the same amount of food,” said Dr Green. “They also had less body fat and fewer fat deposits accumulating inside their bone marrow – a process that is commonly seen after menopause and is linked to declining bone health.”

The team also examined brain tissue and found that the drug appeared to reverse several menopause-related changes in fatty acids.

Levels of beneficial omega-3 fats, including DHA, remained largely intact while other lipid abnormalities shifted towards healthier patterns.

These findings could broaden interest in CADD522 because they suggest its effects may extend beyond the skeleton. However, the researchers did not directly test whether the changes affected memory or cognitive function.

“We didn’t directly test for memory or thinking ability, but our work raises questions about whether this drug could one day help address wider menopause-related health problems,” said Dr Green.

What happens next?

The biggest question is whether the findings will translate to humans.

Safety experiments in mice, rats and dogs found that CADD522 could be administered orally and was well tolerated. Researchers also saw that the compound appeared to be metabolised more slowly in human tissue than in rodents, which could potentially affect how long it remains active.

To move to the next stage, clinical trials will be needed to determine whether the improvements seen in mice can translate into stronger bones and, ultimately, fewer fractures.

“This is still in the early stages and has so far only been tested in animals but we hope that the benefits will translate to humans to ultimately reduce fracture rates,” said Dr Green.

If reseachers can establish exactly how CADD522 produces these effects and whether they can be reproduced safely in people, the compound could open up a new direction for osteoporosis drug discovery.