Is there a causal link between the Metabolic Syndrome and the development and/or progression of Osteoarthritis?
Osteoarthritis (OA) is a prevalent chronic joint disease generally affecting either the knees, hands, spine or hips. Ageing and obesity induced increased mechanical load of joints are reported to be the risk factors contributing to the development of OA. However, obesity is also seen as a risk factor in osteoarthritis affecting the non-weight bearing joints like hands, suggesting that not only mechanical load but even metabolic factors may play an important role in the obesityand osteoarthritis link. This has contributed to a keen interest amongst researchers to establish any causal relationship between the Metabolic Syndrome (MetS) and OA.Metabolic syndrome is a phenotype characterised by central obesity and a combination of metabolic dysfunctions such as hypertension, hyperglycaemia, and dyslipidaemia (low HDL and triglyceridemia).
A lot of published literature indicates thatmetabolic change augmentsthe chances of developing osteoarthritis. . Metabolites involved in energy, lipid and carbohydrate metabolism in the OA patients were reported to be significantly altered compared with those with little or no evidence of the disease (Qingmeng Zhanget al., 2015).The involvement of proinflammatory adipokines in the onset and progression of OA was reported suggesting additional metabolic factors are involved rather than just mechanical stress on the joints (Javier et al., 2013, L.K.Kinget al.,2015). Synovial cells can also be triggered by oxidized LDL to release growth factors and proinflammatory cytokines which cause cartilage destruction and bone deformations in OA (Wouter de Munteret al., 2016). Additionally, lipidbuild up in the cartilage can impair cholesterol efflux in chondrocytes, hence inducing OA (Tsezouet al., 2010). As parts of the metabolic syndrome, insulin resistance, hyperglycaemia, and hyperinsulinemia are also strongly related to OA pathogenesis. Georg Schettet al.,(2013) conducted a population-based cohort study followed over a period 20 years which diabetes to be an independent predictor for osteoarthritis.Oxidative damage,endothelial dysfunction, inflammation and altered metabolism are pointed out to be the shared pathophysiological channels in osteoarthritis as well as MetS. (J. Sellam and F. Berenbaum ,2013) (Q. Zhuo et al.,2012) (D. M. Findlay,2007) (T. Simopoulouet al., 2007).The above studies not only establish a connection between the components of MetS and OA but also suggest its involvement in progression of the disease. However, the causal link will hold significance only if the obesity-related load to some extent is adjusted for while assessing the influence of metabolic syndrome and its components on OA. Hussain et al.(2014) found that abdominal obesity and hypertension,independent of BMI were associated with a high prevalence of knee osteoarthritis, and also stated that accumulation of MetS components in an individual increases the risk of OA.However, the same correlation could not be established for hip osteoarthritis in both the above studies In contrast,some studies revealed that all MetS components had a strong connection with knee OA but after adjustment for BMI, almost all of these links became insignificant. (JingboNiu et al.,2017) .Yoshimura et al. (2012) also reported that the association of systolic blood pressure and hyperlipidaemia with Knee OA proved to be trivial after adjusting for BMI. Moreover, this study also confirmed that gradual build-up of MetS components increases the occurrence of Knee OA. DoosupShin (2014) established the relationship between MetS and knee OA on the basis of excessive weight only and not by insulin resistance, a key pathophysiology of MetS.As in the previous studies, in this study also, the association of other MetS components, abdominal obesity and high BP with knee OA became nonsignificant after adjusting for weight or BMI. Osteoarthritis - another component of metabolic syndrome (MetS) OA is also one of the cluster components of MetS ,hypothesised by a few researchers (VelasquezMTand Katz JD, 2010). Q.Zhuoet al. (2012) examined the likely shared pathogenesis between the MetS and knee OA that supports the inclusion of OA as a component of MetS. Available evidence supports that accumulation of components of MetS increase the risk for knee osteoarthritis. Thus, metabolic factors contribute greatly to the pathogenesis of the heterogeneous condition, osteoarthritis. Also, all evidences were related to knee Osteoarthritis, and no studies established a firm link with hand, hip or spine osteoarthritis. However, as there are contrasting results with positive relation between MetS components and OA, after adjusting for BMI, no direct causal link can be established between the two.
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