The mysterious decline of Paget's disease: a link to coal?

Paget's disease is more prevalent in certain geographical regions, such as Western Europe, Australia, and New Zealand. Surveys in the 1970s showed that the UK had a substantially higher number of people affected (prevalence) by Paget’s disease than any other country. In the late twentieth and early twenty-first centuries, studies documented a rapid and unexplained change, with a greatly reduced prevalence and less severe disease.

There have been many theories into the causes of Paget’s disease and research (including work supported by the Paget’s Association) has identified clear links with mutations in several genes, notably SQSTM1. Genetic predisposition alone, however, does not account for the overall decrease in Paget’s disease cases or the less severe presentations observed in recent times. It is thought that environmental factors, such as diet, toxins, chemicals or infectious agents, might play a role. There have been many scientific papers published that discuss these potential factors. In 1974, a paper tentatively suggested that improved vitamin D nutrition in childhood might be relevant, but Professor Cundy thought that unlikely and given that vitamin D deficiency is seen all over the world, it would not explain the distribution. Viruses have been long explored as a possible trigger, including canine distemper and measles but these infections occur worldwide. Immunisation (of dogs) against distemper began in the late 1950s and immunisation (of humans) against measles began around 1969, which was too late to explain the recent decline in the prevalence of Paget’s disease. Professor Cundy wondered if the environmental factor might be a pollutant. It was suggested in 2002 that calcium arsenate toxicity related to the cotton mills in Lancashire might be significant. Calcium arsenate was used on cotton plants as an insecticide between 1923 and 1945. The thought was that this could have contributed to the decline in prevalence between surveys carried out in the 1970s and 1990s but it didn’t explain the decline in prevalence in other parts of Britain or other countries. In Quebec, Paget’s disease has been associated with mining and wood-burning fires (Quebec has mines producing niobium, copper, titanium, gold, zinc, copper, silver and graphite but not coal). Its prevalence in Quebec is also declining.

Professor Cundy proposed that there could be a link between the decline of Paget’s disease and the reduction in domestic coal use. Using data on coal production, population size, and approximations of domestic use, the estimated exposure to domestic coal burning rose threefold in Britain during the nineteenth century and began to fall after 1900 following the industrial revolution and subsequent period of great change. Rapid industrialisation was driven by the use of coal for energy and, in the home, bituminous coal was customarily burnt on an open hearth for heating. The pattern of coal use fits with the decline in Paget’s disease documented by death certification and prevalence surveys.

Colonists moving from the UK to North America, Australia and New Zealand established coal mines and also used coal for domestic heating. Paget’s disease was found in these settler populations but was largely absent from people indigenous to these lands. All over the world, the prevalence of the condition has fallen, as the burning of coal in open hearths for domestic heating has fallen. The exact substance in coal that might have triggered the disease is unknown. Possible candidates include both organic and inorganic constituents of bituminous coal.

The coal hypothesis does not exclude the possibility that other factors could be important. While environmental factors may trigger Paget’s disease, genetic factors play a significant role, particularly as sporadic cases become rarer. There is also the possibility that Paget’s could emerge without a trigger, particularly when there is a strong genetic driver.

So, could changes in energy use, particularly coal, be a key factor in the mysterious decline in Paget's disease? It is plausible but the evidence remains circumstantial. Professor Cundy concludes his article by saying, “The coal hypothesis raises as yet unanswerable questions and the hypothesis outlined in the paper, suggesting a link to rapid industrialisation and implicating domestic coal use, is probably untestable at the population level, given the worldwide change in coal usage. However, this hypothesis could stimulate further research into the biology of the disease.”

Reference

Cundy, T. (2024) The Decline of Paget’s Disease of Bone and Domestic Coal Use—A Hypothesis. Calcified Tissue International, 115, 117–123.