Summary of the Contribution of Nutrition and Rationale for the Present Study

Despite the various biomechanical, genetic, endocrine and inflammatory factors that influence osteoarthritis and pain, the eitopathogenesis of OA still needs clarification (Pavelka 2017). Although there are many of studies contributing to the knowledge of diet and nutrition with a focus specifically on OA and associated symptoms, further

investigation is needed and replication and validation of results in other datasets should also be conducted to confirm findings (Deutsch 2007). More research into this area could result in lifestyle improvements and better health and wellbeing opposed to a lifestyle of surgery, drugs, interventions and side effects. Studies are needed to investigate those who respond to nutrition and those who do not. Future studies also need to assess the risk factors, at the rates at which they are reduced, in those whose primary treatment is dietary intervention (Dean and Gormsen Hansen 2012). By promoting healthy nutrition, less saturated and trans-fat content would exist in the diet, which is the suggested mechanism by which inflammation is caused through being overweight (Liu, Wei et al. 2013). By changing lifestyle factors, such as nutrition, as a way of treating inflammation and alleviating symptoms there is potential for reducing the rate of the development and progression of OA.

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Many types of studies exist, from cell culture to identify compounds of interest and

laboratory studies to improve our understanding of the mechanisms of action to metabolic studies which look into the physiologic effects. However epidemiologic studies are needed to look at the relationship between diet and disease directly (Willett 2012). Further research into diet and nutrition and the finding of potential associations could lead to the identification of certain aspects of diet that may be able to alleviate symptoms or slow the progression of OA. It may also provide information before onset and therefore reveal a dietary prevention strategy easily implemented on a population scale. New evidence (although limited) is emerging through the literature regarding nutrition and OA but these effects and the relationship between nutrition and OA/pain need clarifying. Further research is needed before there is certainty about specific associations seen between diet and OA and the direction of causality between these associations.

Research investigating lifestyle factors has improved over recent decades as large

population based data resources have become available. These include cohorts such as the European Prospective Investigation into Cancer (EPIC), TWINS-UK, the Rotterdam Study, the Chingford Study and the Osteoarthritis Initiative (OAI). Detailed phenotypic information on the clinical features of OA and OA pain such as radiographic data and clinical symptoms together with extensive data on dietary exposures, relevant lifestyle factors such as smoking and physical activity and genetic data from GWAS exist. These large population data sets act as very useful resources for investigating OA. They are sufficiently powered due to their large numbers and are prospective cohort studies which identify exposure at present and determine future disease onset as opposed to being retrospective which arguably are quicker and more cost efficient but relies on sufficient information being available on past exposure, current exposure and risk factors. Therefore prospective cohort studies are considered the most powerful methodology as limitations such as recall bias etc. do not affect the cohort and can also account for changes to exposure status (Silman and Macfarlane 2002). These studies are also of longitudinal design with follow-up of participants and collection of additional data allowing further study of disease over multiple time points. This produces more reliable results than cross-sectional analyses where data is investigated at a single point in time.

With these cohorts, research into diet and its effects on OA and pain can take place, increasing our knowledge of the contribution of various risk factors towards OA. In

particular through investigating SNPs of interest, helping to identify those more at risk and leading to new ideas for treatment (preventative or otherwise). With OA causing dramatic changes to lifestyle, leading to other health problems and with numbers in the population showing it to be on the increase there is a need to investigate potential ways in which patients may be able to change aspects of their lifestyle in order to alleviate their symptoms successfully.

In summary diet and nutrition is able to influence the underlying mechanisms such as inflammation involved in OA and research is ongoing into finding those dietary components that could have pro or anti-inflammatory effects. However more research is needed

specifically into the associations that exist between nutrition and OA/pain for which

sufficient dietary data is needed. Two of the large cohorts above, TWINS-UK and a subset of the EPIC cohort (EPIC-Norfolk cohort) are used in this research to provide additional insight into those lifestyle and dietary factors that play a role in OA and the onset of pain.

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There are numerous studies on the Mediterranean diet and it’s suggested protective association with chronic diseases that are underlined by inflammaging. However, as discussed in Chapter 1, there are a very limited number of studies looking at associations between Mediterranean diet and OA specifically. Most of these studies have focused on knee OA and have also been of cross-sectional design so further studies are needed to investigate associations between dietary factors and OA particularly of other joints,

especially non weight bearing joints such as the hand. The effects of dietary factors on pain have also been investigated previously but there is limited research looking at the effects of diet on pain specifically associated with OA. The TWINS-UK cohort is a great resource and provides a large volume of dietary data, from which a Mediterranean dietary pattern can be created, as well as radiographic OA and musculoskeletal pain data. This will allow an analysis of the analysis of dietary and OA/pain variables in order to further the knowledge of how diet as a modifiable factor may influence the onset or progression of OA and associated pain. In addition this research provides an opportunity for associations to be looked at in greater detail through analysis of genetic data from EPIC which allows for causal mechanisms to be investigated holding the potential to confirm the direction of causality between associations observed.

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