Is the Decline of Paget's Continuing in the UK?

Mr Michael Cook and Professor Terence O’Neill, from the University of Manchester, discuss below research funded by the Paget's Association that was published in April 2021, looking at the occurrence of Paget’s disease in the UK. Professor O’Neill is the director of the Paget’s Association’s Centre of Excellence in Salford. [2021]

Research conducted in the 1970s and 1980s indicated that Paget’s disease was more frequent in the UK than elsewhere in the world, and within the UK was most frequent in the North West of England. Research suggested also that the disease appeared to be declining in frequency. The reason for the geographic variation in occurrence and also the decline in frequency was unexplained. There have been no recent data on trends in the disease in the UK and so it remained unknown whether the disease has continued to decrease in frequency and whether it remains more common in the North West region.

Supported by funding from the Paget's Association

Using grant funding from the Paget’s Association and the Michael Davie Research Foundation, we conducted a research study to look at this. We analysed data from a large primary care register, which included records of over 11 million people in the UK. We looked at people who were newly recorded as having been diagnosed with Paget’s disease, and using this information we were able to work out how the disease varied in frequency in different parts of the country, and also whether it had changed in frequency during the years between 1999 to 2015.

The results of the research have now been published in a peer-reviewed scientific journal. Using the primary care database we found over 3,500 new cases of Paget’s disease in patients aged 18 years and over, who had been diagnosed in the past 20 years. We found, as has been shown previously, that the frequency of the disease increased with age, in both men and women, but was more common in men at all ages. One of the key findings though, was that the frequency of the disease appeared to be continuing to decrease. Compared to 1999, by 2015 the frequency of diagnosed Paget’s disease had declined by over 60% to just over one in 50,000 people per year. This decrease in frequency was seen across all parts of the country, though interestingly it remained more common in the North West of England than other parts of the UK.

The reason for the decrease in frequency is unknown. Paget’s disease is known to be uncommon in people of African, Middle Eastern and Asian descent and it is unclear to what extent the demographic changes in the UK population may have influenced these changes in disease frequency. Unfortunately, this is not something that we were able to look at in the present study.

About one in eight affected individuals have a family history of the disease, and research studies have identified a number of genetic variants which predispose to the disease. Although genetic factors are important, the decrease in disease frequency that we have observed, suggests that there have been changes in environmental triggers for the disease over recent decades. Little is known about the influence that environmental factors have in Paget’s disease but several potential factors have been suggested such as vitamin D deficiency, poor dietary calcium intake, and exposure to environmental toxins. The only factors that have been studied experimentally in detail are viral infections. There have been some suggestions that chronic infection with measles virus, canine distemper virus and respiratory syncytial virus may be involved in Paget’s and it has also been found that people with Paget’s have higher levels of antibodies to the mumps virus than unaffected individuals. However, studies on the role of viruses have so far yielded inconclusive results.

We wondered whether poverty or levels of socio-economic deprivation might be important and looked in the primary care database at whether the frequency of disease varied by socioeconomic status. Using a widely used marker of socioeconomic status (known as the index of multiple deprivation) our results showed that the disease did vary by poverty levels, with the frequency of disease 30% higher in the most, compared to least deprived areas. How social class may influence the disease is unclear, though this is probably due to either increased exposure or susceptibility to one or more other environmental triggers, including possible viral infection.

We wondered whether the excess of Paget’s disease in the North West of England might be explained by differences in levels of socioeconomic deprivation, however, when we analysed the data we found that the higher frequency in the North West persisted, even after taking into account levels of deprivation, and so the reason for the North West excess remains unknown and for which further research is needed.

Our research focused on people who had been diagnosed with Paget’s disease. The majority of people with the disease are asymptomatic and have not been diagnosed. Our findings though, in relation to the decrease in frequency of diagnosed disease, are consistent with results of a couple of recent small x-ray surveys, which suggest there has been a decline in the overall frequency of disease.

We thank the Paget’s Association and also the Michael Davie Research Foundation for supporting the research.

Michael J Cook, Terence W O’Neill; Centre for Epidemiology Versus Arthritis, Stopford Building, University of Manchester, Manchester, UK

Reference: Cook, M., Pye, S., Lunt, M., Dixon, W., Ashcroft, D., O'Neill, T., Incidence of Paget’s Disease of Bone in the UK: Evidence of a Continuing Decline. Rheumatology, 2021.