Organophosphate insecticides and the skeleton

Stephen Hodges

Acute exposure to organophophate insecticides (OPs) is well known to cause health problems. But less is known about the effects on health of long-term chronic exposure. Work to investigate them is given no central support: it is only possible with the assistance of groups such as PEX and OPIN, the OP Information Network.

Some of the members of both groups have been involved in a study to investigate the possible effects of these chemicals on the skeleton. As a tissue, the skeleton can tolerate a lot of insult; if it did not, we would all be in a sorry state! It has been found that OPs are potent agents on the way bone cells function in the test-tube. For this reason, a screen of the skeletal health of men reporting health problems from working with OPs was done. We had 88 sheep-farming volunteers and 43 control subjects, the latter being recruited from urban environments and not having notable exposure to OPs. The farmers were slightly older, but their weights were not different from the control subjects. All the men were given rigorous exclusion criteria to meet so that we could exclude other possible causes for skeletal health problems.

The primary test was for the amount of bone in the skeleton at the wrist, spine and top of the femur. The measurement can be expressed in different ways, but the most common way is to refer to the bone mineral density (BMD) at a given site. This is done using a non-invasive technique. The machine that measures BMD has been well characterised, so there are very low errors in the measurements.

After correcting the BMD results for the age difference between the two groups (as we all age our BMD decreases), we found that farmers and controls had very similar BMDs at the spine and wrist. The farmers were found to have significantly lower BMD at the top of the femur.

The biochemistry of the men was also taken into account to determine if there were other subtle factors that may cause the farmers to have lower BMD. Having taken these 'clinical' precautions, we then biased the statistics away from the farmers. But the results were the same.

The importance of the study may be that the results are difficult to refute. But what do they indicate? Firstly, they do not mean that all people using OPs are going to suddenly break any bones. Indeed, although the difference was what would be called 'statistically significant', it does not translate into a flush of 'hip fractures' in 15 to 20 years' time. 'Hip fractures' are actually fractures across the top of the femur. Men present about a 6 per cent life-time risk of having a hip fracture, so the worst case scenario is only a modest increase in this risk.

So how do OPs affect the skeleton? We don't know. There are cells that remove bone as a natural - and very necessary - part of bone metabolism, and there are cells that replace bone. These cells work in concert. If you tip the balance in this process you have skeletal health problems. In the test-tube we have found that very low levels of OPs can cause increased removal of bone by the specialist cells that do this job normally. This only happens in the presence of vitamin D, and vitamin D levels increase by exposure to sunlight. Dipping on a summer's day may involve a combination of factors that activate increased bone removal.

We do not yet know about the skeleton of farmers who have a bit of 'dipper's flu' after dipping, but have not been incapacitated by their work. We do not know if farmers using OPs are losing bone faster than their urban counterparts. We do not know if farmers have a different non-traumatic fracture rate compared to controls. And we do not know if the genetic factors controlling OP breakdown has predisposed some people to present with health problems. This last point needs to be considered by comparing an objective measure against an objective measure: any degree of subjectivity would cloud the issue. BMD against genetic factors would do this.

[As published in PEX Newsletter No.4, September 1999]