Professor Rob Layfield summarises how wide-ranging and impactful some of the research funded by the Paget’s Association has been in recent years. 

Empowering patients and doctors

For decades, people living with Paget’s disease often left their GPs or clinic with outdated advice. Some were told to expect inevitable deterioration. Others were prescribed treatments that didn’t address their main symptoms. Sometimes doctors weren’t always confident in how to manage the condition and patients struggled to find reliable information.

Hopefully, that’s now changing, thanks in part to the first comprehensive clinical Guideline for Paget’s Disease in Adults, published in 2019. The Guideline, shaped by scientific evidence and patient feedback, lays out clear recommendations for diagnosis and management. It was developed with support from the Paget’s Association, alongside international partners. The result? Doctors now have an authoritative reference that helps them decide when to investigate further, when to prescribe medication and when to reassure.

Patients, meanwhile, gain access to resources that strip away the myths and empower them to have more confident conversations in the consulting room. If patients and doctors are both equipped with the right information, decisions become better and outcomes improve. This links to our current PagetAlert campaign which includes the ambition to reduce the time taken to obtain a diagnosis. Plans to update the Guideline, in particular in light of outcomes of clinical trials that considered the importance of genetic testing (see below), will hopefully continue this positive change.

Listening to patients: pain in Paget’s

One of the most striking insights from recent research is that pain in Paget’s disease isn’t always caused by the Paget’s itself. In a large study of people living with the condition, led by the University of Edinburgh and supported in part by the Paget’s Association, nearly three-quarters of participants reported persistent pain. But when researchers looked more closely, they found that much of the pain came not from overactive Paget’s bone lesions but from other causes, particularly osteoarthritis.

This matters enormously. For years, the assumption was that controlling Paget’s disease activity with drugs like bisphosphonates would also relieve pain. For many, however, that approach failed, supporting the notion that patients need holistic care, not just bone scans and drugs, but proper pain assessment and support for related conditions.

By highlighting this issue, the research has shifted the focus of treatment. Doctors are increasingly alert to investigating other causes of discomfort, ensuring patients don’t slip through the cracks. For some of those living with daily pain, that shift can hopefully mean the difference between years of frustration and finally getting relief. Again, central to our current PagetAlert campaign is the goal of ensuring pain is properly managed.

Searching for causes

Despite its long history, Paget’s disease was first described by Sir James Paget in 1877 (see page xx for more detail) but the exact causes remain a puzzle. Why do some people develop it and not others? Why are cases more common in some parts of the UK than others and why has its incidence fallen so dramatically over the past two to three decades?

Large-scale epidemiological studies are helping to piece together the answers. Work in Salford and Manchester, supported by the Paget’s Association, found that the number of new diagnoses has plummeted, from around 0.75 per 10,000 people in 1999 to just 0.20 per 10,000 in 2015. The sharp decline hints that environmental factors, perhaps something in the diet, exposure to infection or some other environmental toxins may play a role.

Other work shows intriguing geographic patterns. The North-West of England has consistently recorded higher rates of Paget’s than other regions. Within Greater Manchester, the researchers also found that prevalence was higher among people living in more deprived areas and that diagnosis varied by ethnicity. They found it was more common in Black or Black British populations and less common in Asian or Asian British groups. The reasons for these variations are still unclear, but the findings underscore a vital point: diagnosis is uneven. Some communities may be underdiagnosed, while others face higher risks without knowing why.

Unlocking the environmental and social factors at play could be the key to prevention in future generations. This ties in with research funded by the Paget’s Association into ancient Paget’s disease at Liverpool John Moores University, building on previous work from Nottingham, which aims to identify potential environmental triggers for an unusual form of medieval Paget’s disease discovered at Norton Priory in Runcorn.

Families and genes

While environment matters, there’s also a clear genetic dimension to Paget’s disease. Around one in five patients has a family history of the condition and variants in a gene called Sequestosome-1 are strongly linked to its development. Recent clinical trials led by The University of Edinburgh (in which former Trustee of the Paget’s Association Professor Bill Fraser, Diana Wilkinson from the Association, and member Keith Charnock served on the trial steering committee) have shown how this knowledge can translate into practical benefits. Relatives of Paget’s patients who carried Sequestosome-1 variants were offered genetic testing. Those who tested positive were then given early monitoring and some received preventative treatment with zoledronic acid. The results were encouraging - genetic testing combined with proactive treatment reduced the chances of Paget’s developing or progressing. For families, this approach offers reassurance and a sense of control. Instead of waiting for symptoms to strike, they can take steps in advance.

This finding is a real milestone, showing it’s not just about treating the disease once it appears, but rather giving families peace of mind and potentially stopping Paget’s before it causes damage. A priority of the Association is to encourage debate and new research to evaluate potential genetic testing, to identify those at most risk.

Building better models 

For researchers trying to study Paget’s disease in the lab, there has always been a frustrating problem: you can’t easily replicate it in simple cell culture models, as bone cells are so highly specialised. Without accurate models, testing new treatments or probing the underlying biology has been slow and uncertain. That may now be changing. With support from the Paget’s Association, now picked up by the Medical Research Council, researchers at the University of Oxford are developing fully human 3D bone models. These lab-grown structures mimic the complexity of real bone tissue, providing a controlled environment where Paget’s mechanisms can be observed and potential drugs trialled.

This is like moving from a sketch to a working model, a system that behaves much more like human bone. It opens the door to experiments we simply couldn’t do before. Over time, these models could accelerate the development of targeted therapies, replacing ‘trial-and-error’ with precise, personalised treatment.

Why it matters

All this research, from guidelines and genetics to pain management and bone models, has one common thread: it starts with patients. The Paget’s Association has made sure its priorities reflect the voices of those living with the condition. Surveys of members helped shape the research agenda. Patient representatives sit alongside scientists on trial committees. And the findings are shared not just in scientific journals, but directly with the community, through our website and this magazine.

That patient-centred approach is paying off. For those diagnosed today, the landscape looks very different from just a decade ago. There’s clearer advice, greater awareness of pain management, new insights into risk factors, and real hope that families might one day avoid the disease altogether. Still, challenges remain. Many cases are missed, especially in underserved groups. The environmental triggers remain elusive and while treatments can control the disease, there’s no cure. That’s why continuing investment in research is vital.

What we’ve learned

Diagnosis

Clearer guidelines mean doctors and patients can finally speak the same language about Paget’s.

Pain

Pain isn’t always caused by Paget’s itself — osteoarthritis and other conditions are often to blame.

Causes

Paget’s is declining rapidly, hinting at environmental triggers we don’t yet understand.

Families

Genetic testing offers the potential for peace of mind for families and the chance to stop Paget’s before it starts.

Models

Lab-grown 3D bone opens the door to studying Paget’s in ways we never could before.

Patients first

When patients’ voices guide research, the results change real lives.