What prompted you to start the research that became your highly cited 1992 Osteoporosis International paper on hip fractures in the elderly?

At that time, we had started to see rates of hip fractures from epidemiologic studies around the world published in the literature. Each study was generating its own age- and sex-specific incidence rates, but no one had brought all that together and used it to calculate the global burden of disease in 1990 and then to extrapolate or predict what that burden would be in 2025 and again in 2050. So we assembled all the data in the literature. By then, that included over 100 studies published from different areas of the world. We got population projections from the World Health Organization and the U.S. Bureau of the Census, and we estimated for future years what the hip fracture burden would be.

  And what did you find?

First of all, the paper gave the exact numbers for the incidence of disease: it said that 1.6 million hip fractures a year in 1990 would become over 6 million by 2050 and then it explained that the location of those fractures would change markedly over that 60-year period. In 1990, we were seeing hip fractures mainly in Western nations: in North America, Europe, Australia and New Zealand, but by 2050 over half would be in Asia and a substantial proportion in Latin America because of the exploding numbers of elderly and rising hip fracture rates being observed in those populations. So the paper, in effect, had two parts. Firstly, it brought together all the rates and, secondly, it showed how there would be a marked demographic shift in incidence from developed to less-developed countries.

  Did you expect the paper to be so highly cited?

We expected it to be significant, but I was surprised that it was that significant. I would have expected it to be among my top 10 cited papers, but not the top of the top 10. I think the reason it’s been cited so frequently is simply that nobody had ever estimated the global burden of this disease until then. This was the first proper assessment of the global burden and the first projection that was done well and robustly for 60 years into the future. The reason it has stood the test of time—if you look at its citations, it’s still cited quite often—is because it was done well and it still remains among the very few papers to project so far into the future.

  2050 seems like a very distant horizon for a reliable prediction. Why did you go so far into the future?

Because that’s the period during which we will see big differences in demographic changes around the globe. If you look at patterns of disease in developed countries, you have to look over time frames of 50 to 100 years to see major changes. The rates of disease are not variable enough to change over four or five years. You need to look at long-term temporal trends.

  How has your research evolved since then?

  How do you see osteoporosis research changing in the next decade?

I think the developmental origins aspect is going to explode. We have just won financial support to research the developmental origins of chronic diseases. That idea is known as the Barker hypothesis, after Professor David Barker who is here at Southampton, and he has shown that fetal development plays an important role in heart disease and diabetes. I have extended this research into osteoporosis. So Southampton is the world center for that. We had the first International Conference of Fetal Origins of Chronic Disease in India last year, and the second will be held in Brighton, England, next summer. That whole area—childhood growth, maternal well-being, and assessing how best to intervene in the later manifestation of osteoporosis—is a major research agenda. As a result, I think osteoporosis research will move toward studying the disease in younger ages and into trials that test different interventions during pregnancy to influence the bone mass of the newborn. Those sorts of areas are really going to develop fast. And those will entail the understanding and exploitation of the human genome project. We know that there are a number of genes that are candidates for the increased risk of osteoporosis. For most of those, we don’t know yet how they work or what role they play. But this whole area of exploiting the genes of development is going to explode as part of the program on early origins of osteoporosis.

  Has there been an element of serendipity to your work?

Certainly, there has been in this fetal origins research. I can’t think of a more serendipitous one. Here we have David Barker demonstrating the fetal origins of coronary heart disease. I looked at a map of hip-fracture incidence and saw that it shows a strong relationship with the map of heart-disease incidence, and so I started looking at individuals for an association between low birth rate and osteoporosis, and there it was.

That together with a small group of key investigators around the globe, I have contributed at an international level to creating an entire field of study, osteoporosis, which was simply ignored up until 20 years ago. There has been a small core of very active, highly productive investigators, maybe 40 or 50 around the world (of whom I am privileged to be one), who have worked in osteoporosis research over the last 20 years and have created a thriving scientific field. That is a wonderful sense of achievement. When I started in this field, osteoporosis was a disease that commanded an annual conference attendance of 100 people. In 20 years, we have turned it into one that commands an annual conference attendance of 6,000 people.

It was simply not recognized that fractures were such a large problem, because the relevant epidemiology had not been well worked out. We also had no means of measuring bone density and we didn’t have a range of treatments to retard bone loss. So even if people conceded there was a problem, there was no real strategy for how to resolve it. The disease was seen as an inevitable consequence of aging. Then three things happened: first, we mapped out the huge burden of fractures around the world; then we worked out ways of measuring bone density non-invasively, and we developed all these new drugs to prevent bone loss. Those things coming together led the field to suddenly explode.