Biomarkers of Osteoarthritis—A Narrative Review on Causal Links with Metabolic Syndrome

Abstract

Development of OA (OA) is multifactorial and is strongly associated with risk factors such as aging, trauma, metabolic disorders, and obesity. Metabolic Syndrome (MetS)-associated OA, collectively coined MetS-OA, is an increasingly recognized entity in which metabolic disorders and low-grade inflammation play a key mechanistic role in the disruption of joint homeostasis and cartilage degradation. Although there have been enormous efforts to discover biomarkers of MetS and OA, studies investigating a pathophysiological link between MetS and OA are relatively limited, and no serum blood marker has proved diagnostic so far. OA biomarkers that are necessary to discriminate and diagnose early disease remain to be elicited, explained in part by limited prospective studies, and therefore limited tools available to utilize in any prognostic capacity. Biomarker validation projects have been established by the Biomarker Consortium to determine biochemical markers demonstrating predictive validity for knee OA. Given that the metabolic constituents of MetS are treatable to varying extents, it stands to reason that treating these, and monitoring such treatment, may help to mitigate deleterious links with OA development. This narrative review will describe the current state of biomarker identification and utility in OA associated with MetS. We discuss the pathophysiological mechanisms of disease according to constituent pathologies of MetS and how identification of biomarkers may guide future investigation of novel targets.

PLOD2 gene expression in infrapatellar fat pad is correlated with fat mass in obese patients with end-stage knee osteoarthritis

“…Obesity is known to correlate with a chronic low-grade systemic inflammation providing a potential link to OA pathogenesis [ 8 , [15] , [16] , [17] ]. Epidemiological studies have identified associations between OA and obesity-linked disorders [ 8 , 9 , 18 , 19 ].…”

“…The dysfunctional adipocytes and adipocyte necrosis observed in obesity lead to the infiltration of proinflammatory cells, including macrophages, mast cells, and specific T cell subtypes [ 13 , 14 ]. This inflammatory process is distinguished by abnormal cytokine production, elevated levels of acute-phase reactants, and the activation of a network of inflammatory signaling pathways providing a potential link to OA pathogenesis [ 8 , [15] , [16] , [17] ]. Epidemiological studies have identified associations between OA and obesity-linked disorders, with the most substantial relationships observed between type 2 diabetes or hyperglycemia and OA, resulting in a 43% increased overall risk [ 8 , 9 , 18 , 19 ].…”

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

“…However, it is clear that OA is an inflammatory disease (discussed in [51][52][53][54]) and in early post-traumatic knee injuries leading to OA in preclinical models, treatment to inhibit inflammation ameliorates the development of the condition [55][56][57]. Furthermore, metabolic osteoarthritis has an inflammatory component [58][59][60] and this may relate to post-menopausal women with obesity.…”

Obesity, Metabolic Syndrome, and Osteoarthritis Require Integrative Understanding and Management

“…In animal models of OA, irisin administration was able to reduce cartilage degradation and circumvent inflammation possibly by regulating mitochondrial biogenesis and supporting autophagy dynamics [ 153 ] and pointing towards a possible role as therapeutic intervention in OA. Patients with OA have lower circulating levels of irisin compared to healthy controls, suggesting a potential protection against joint degeneration and role as a serum biomarker [ 154 ].…”