Incidence of total knee and hip replacement for osteoarthritis in relation to the metabolic syndrome and its components: A prospective cohort study
Introduction
Osteoarthritis (OA) is a major health problem with significant morbidity and disability associated with OA of the knees and hips. OA resulted in a total of 71.1 million years lived with disability in 2010, an increase of 64% since 1990 [1]. Although several drugs and nutriceuticals have been evaluated in clinical trials to determine whether they are able to slow the structural progression of OA, currently there are no registered disease-modifying OA drugs. Therefore, understanding the role of modifiable risk factors is important for improving prevention. Obesity [high body mass index (BMI) or waist circumference] is widely recognised as the most important modifiable risk factor for knee OA [2], [3], although the evidence for hip OA is less consistent [2], [4]. The available evidence suggests that obesity increases the risk of OA through both increased loading [5] and metabolic mechanisms [6], [7].
There has been an increasing interest in the relationship between OA and the metabolic syndrome (MetS), the clustering of abdominal obesity, dyslipidaemia (low high-density lipoprotein (HDL) and triglyceridaemia), hyperglycaemia and hypertension [8]. MetS was found to be 5.26 times more common in those with OA compared with those with no OA, and the individual components of the MetS were also more prevalent in people with OA in the NHANES III survey [9]. However, the Malmö Diet and Cancer study reported only central obesity to be associated with increased risk of knee OA independent of BMI, and neither MetS nor components of MetS to be associated with hip OA [10].
The Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) 3-year follow-up study focused on the relationship between components of MetS defined as obesity measured by BMI, hypertension, dyslipidaemia and IFG with the incidence and progression of radiological knee OA in a Japanese population [11]. They reported that BMI, systolic blood pressure and dyslipidaemia were associated with incident knee OA [11], but the associations for systolic blood pressure and dyslipidaemia were no longer statistically significant after adjusting for BMI [11]. Moreover, this study found an increased risk of knee OA progression associated with an increase in the number of MetS components [11].
There is now an increasing body of evidence from epidemiological, proteomic, genetic and in vitro studies examining potential shared pathogenic mechanisms between the MetS and knee OA [12], [13] that supports the inclusion of OA as a component of MetS [13], but it is still unclear whether MetS is a pathway to OA or whether OA and MetS simply coexist through commonly shared risk factors of age and obesity.
One method for defining OA is based on joint replacement [4], [10]. This definition signifies severe clinical knee and hip OA, which is relevant to the symptomatic disease burden and economic impact of OA. Thus, in a large prospective cohort study, we examined the relationship between the components of MetS and the accumulation of components of MetS and the incidence of total knee and hip replacement due to severe OA.
Section snippets
Study participants
The Melbourne Collaborative Cohort Study (MCCS) is a prospective cohort study of 41,514 participants (24,469 women) between the ages of 27 and 75 years at baseline [14]. Participants were recruited via the Electoral Rolls, advertisements and community announcements in local media, between 1990 and 1994. Southern European migrants to Australia (including 5411 Italians and 4525 Greeks) were deliberately oversampled to extend the range of lifestyle exposures and to increase genetic variation. The
Results
A total of 1222 total joint replacements (660 total knee replacements and 562 total hip replacements) performed for OA were identified between the 2003 and 2007 follow-ups and December 31, 2011. The mean follow-up duration was 6.8 (SD 1.5) years. There were differences in relation to the distribution of age, sex, BMI, waist circumference, prevalence of hypertension, impaired fasting glucose, country of birth, education and physical activity between the attendees and non-attendees of the
Discussion
In a large prospective cohort study, we found that the MetS and its components, central obesity, hypertension, low HDL, triglyceridaemia and IFG were associated with increased incidence of severe knee OA requiring total knee replacement. Following adjustment for BMI, a measure of overall body size, the associations of central obesity, hypertension and the MetS remained significant. With the accumulation of MetS components, the incidence of severe knee OA increased, independent of BMI. In
Conclusion
The MetS itself and individual components of the MetS, particularly central obesity and hypertension, are associated with increased incidence of severe knee OA requiring total knee replacement, independent of obesity assessed using BMI. Furthermore, accumulation of components of the MetS in an individual increases the risk of severe knee OA, independent of BMI. No such relationship was seen for severe hip OA. Our findings suggest that the pathophysiology of knee and hip OA differ and that
Acknowledgements
The Melbourne Collaborative Cohort Study was made possible by the contribution of many people, including the original investigators and the diligent team who recruited the participants and who continue working on the follow-up. We would like to express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. For the data linkage, we would especially like to thank the Registry coordinator Ann Tomkins and statistician Lisa Miller from the Australian
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Sources of support: The recruitment of the Melbourne Collaborative Cohort Study was funded by Vic Health and Cancer Council Victoria. This study was funded by a programme Grant from the National Health and Medical Research Council (NHMRC; 209057), Capacity Building Grant (251533), and Enabling Grant (396414), and was further supported by infrastructure provided by the Cancer Council Victoria. Dr Wluka is the recipient of NHMRC Career Development Fellowship (Clinical, level 1, #545876).
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Joint first authors.