Osteoarthritis research gets closer to the bone


Professor Nick Fazzalari

11 June 2009

For more than half a century, osteoarthritis research has focused solely on cartilage. But that hasn’t delivered much benefit to most of the 1.6 million Australians who suffer the disease, with many still needing joint replacements. Now there’s a new approach.

Realising they had to think laterally, Professor Nick Fazzalari and his team in Adelaide looked at other tissues associated with osteoarthritic joints. What they discovered was that skeletal bone differences between people who have osteoarthritis and those who don’t make a significant contribution to the disease’s development and progress.

They also investigated molecular signalling in the bone to determine whether natural changes cause osteoarthritis or are merely a response to it. In this podcast, Prof Fazzalari tells Dr Andi Horvath that the goal is to find a way of manipulating the signal pathways at early stages of the disease to stop it from progressing.

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Transcript of podcast

Voice-over: Welcome to this special National Health and Medical Research Council podcast on Ten of the Best Research Projects for 2008. Our podcasts aim to keep you in touch with major health and medical research issues and the people who shape them.

Introduction: Hi I’m Dr Andi Horvath and I have the pleasure of talking to Professor Nick Fazzalari. He’s the Chief Medical Scientist and Head of the Bone and Joint Research Laboratory, which is a division of the Surgical Pathology Unit. He’s connected with South Australia Pathology and Hanson Institute.

Interviewer: Nick thanks for joining us here on the NHandMRC pod project to talk about your adventures. Now tell us about your particular research project. If you could sum it up just very quickly, what is it that you do?

Prof. Fazzalari: We had the opportunity to look at a very common disease in our community, osteoarthritis, and there is little understanding that this disease, as we know it today, is incurable. There are many people in the community that suffer from this condition and at the moment they can be offered some pain relief until the pain becomes unbearable because of the deterioration of their joints, then they have the opportunity to have a joint replacement.

Interviewer: Professor Nick, what formulated your research directions?

Prof. Fazzalari: Because we recognised that the disease was incurable and that many years of research into cartilage, which is the lining on the joint, has not really delivered any significant benefits to the bulk of the population suffering from this condition, we decided that we should think laterally and look at some of the surrounding tissues that are associated with this disease. And we thought that we would look at bone and its relationship to that disease. When we embarked upon the investigations to look at the bone associated with osteoarthritis, we had some indications from the literature that there was something that was different about the bone but it wasn’t clear what those differences were.

Interviewer: What were the research outcomes of this project. What new information do we have that sheds light on osteoarthritis?

Prof. Fazzalari: Our research has shown very clearly that the amount of bone in the skeleton of individuals that have osteoarthritis — this is bone that is away from the joint that has the disease — so these skeletons have more bone than individuals that don't have osteoarthritis. The structure of that bone, which is a spongy type of bone, is different. The material that the bone is made of is also different and underpinning those tissue-level changes is a significant change in the molecular signals that control the bone cell activity to maintain and change the bone, were also found.

Interviewer: Wow, so Professor Nick you're saying that these individuals have slightly different types of bone proportions in different parts of the body and molecular processes that renew the bone are a bit different as well?

Prof. Fazzalari: That's correct, because it's important to understand that the bone is a living organ, it has the ability to change itself during life.

Interviewer: If you're looking into the future, what are you hoping we might be able to do?

Prof Fazzalari: At this stage we're seeking to extend our investigations to look at the signalling — the molecular signalling — that is occurring in the cartilage, to look at what if any is the nature of the conversation between the cartilage which lines the articulating joint and the underlying bone, and to determine whether the boney changes are causing the disease or whether the boney changes are a response to the disease. This stage, based on our NHandMRC-funded study, we feel we have very strong evidence to suggest that the boney component of the skeleton in those individuals with osteoarthritis is having a much more significant contribution to the development of the disease, the progression of the disease and perhaps, in that context, also provide us with yet unthought-of opportunities to try and intervene at the early stages of the disease to stop it progressing, and perhaps the patient ultimately avoiding having to have the surgery that leads to a joint replacement.

Interviewer: So have you identified some of these signalling molecules that are connected to our bone health?

Prof. Fazzalari: What we’ve been able to do is to identify signalling pathways that we think have a significant role to play in the onset and progression of the osteoarthritis disease.

Interviewer: And is the idea to eventually manipulate these signalling pathways early in the disease?

Prof. Fazzalari: That’s the objective.

Interviewer: This is an amazingly complex area of physiology, and could you sum up for us, why do you do this research?

Prof. Fazzalari: Research in osteoarthritis for the last 50 or 60 years has focused on looking and trying to understand what is happening to the cartilage in this disease and a lot of excellent work has been done in this area, but this research hasn’t delivered solutions that affect a significant proportion of the population that has this disease.

Interviewer: Sure and we talk about an ageing population as well.

Prof. Fazzalari: And a bit like somebody drilling for oil. If somebody is drilling for oil and they don’t find it at one kilometre depth they have two choices, they can keep drilling deeper to ten kilometres and still find no oil, and on and on. Or, the alternative strategy is to think laterally, to pack up from that drilling site and move to another site and explore whether there is potential there. And that's what we have done here. We've thought, what are the surrounding tissues of the joint other than cartilage and what sort of role may they have in development of the disease. So that was a very strong motivation, to try and think laterally and to try and perhaps deliver some benefit to the patient in a much shorter time frame.

Interviewer: Professor Nick Fazzalari thank so much for your insights into this NHandMRC research project. Good luck with your work. It certainly is a very relevant issue for today’s ageing population. Thanks for talking to us.

Prof. Fazzalari: Thank you.

Voice-over: This podcast was brought to you by the National Health and Medical Research Council, working to build a healthy Australia. You'll find more information about this and other health and medical research issues on our website at www.nhmrc.gov.au.