Paget's disease of bone in Lancashire and arsenic pesticide in cotton mill wastewater: a speculative hypothesis.

A 1974 survey of Paget's disease of bone in 31 UK towns identified a cluster of six Lancashire former cotton mill towns with the highest prevalence rates of the disease and noted a link with the cotton industry. The two highest-prevalence towns are situated on estuaries and are jointly the smallest of the six by the size of their former cotton industry. The two lowest-prevalence towns of the six are highest above sea level and jointly the largest by the size of their former cotton industry. This pattern suggests a waterborne agent. A 1993 repeat survey of 10 of the 31 towns identified a general decline in prevalence, greatest in the three cotton towns included from the six in the earlier survey, further suggesting a link to the cotton industry. Cotton mills and bleach/dyeworks produced a large volume of wastewater that was commonly discharged into adjacent waterways. Wastewater contained process chemicals and imported organisms and pesticides carried in cotton bales. The process chemicals and imported organisms could be discounted as a probable factor in Paget's disease; however, pesticides could not be discounted. Lancashire cotton came predominantly from the American cotton belt. From 1917 to 1945, calcium arsenate pesticide was used intensively to combat the boll weevil and was imported to Lancashire in cotton bales. The calcium arsenate era is consistent with the high-prevalence findings in 1974 and the decline in 1993, allowing for time lags. Geochemical arsenate is widespread in the environment and may account for geographic variations in Paget's prevalence, although data are inadequate for correlation studies. Noncytotoxic doses of arsenic affect all the steroid receptors and some signal transduction pathways, which may lead to dysfunctional osteoclast signaling and differentiation. Human cells are more susceptible than animal cells to arsenic, based on studies of nonbone cells. It is speculative that arsenic may be a factor in the abnormal variation in prevalence rates in Lancashire. It is not a general theory of Paget's disease.