## 1 Introduction  
Significant expenditures are allocated to the healthcare system, contributing between 10 and 30% of public expenditures [1]. Musculoskeletal disorders make the most significant contribution to the total rehabilitation needs in relation to other pathologies, and due to the aging population, this phenomenon will keep rising [2]. As a challenge, the increasing demands in healthcare underline the need to develop effective strategies to prevent and manage chronic musculoskeletal disorders [2]. Osteoarthritis (OA) is a prevalent chronic disease with the most increasing trends in prevalence and years of life lived with disability [2]. Globally, cases of OA increased more than double, from 247.51 million in 1990 to 527.81 million in 2019 [3]. OA is one of the most common causes of disability in the general population [3, 4], with a high need for the utilization of healthcare services [2]. Symptoms of pain, swelling, and stiffness make movement painful and difficult, leading to activity restrictions. For this reason, most cases are associated with a deterioration in mental health, sleep quality, and social relationships, reducing quality of life [3]. Further,being less physically active increases the risk of cardiovascular diseases, obesity, diabetes, stroke, peptic ulcer [2; 3], and cancer [5], increasing the complexity of disease management and the cost of treatment [4]. The typical onset of the disease is in the late forties or fifties, although osteoarthritis may affect younger people, especially those with a history of traumatic joint injury [3]. The knee joint is the most affected joint, accounting for approximately 61% of all OA cases [3]. About one in ten citizens in their late fifties are affected by symptomatic Knee Osteoarthritis (KOA) in Greece, and this proportion increases progressively with age [4]. The highest prevalence is presented at the age of 75-79 [4]. Current treatment options for KOA in the initial stages of the disease focus on symptom relief and include medications, therapeutic exercises, and medical aids [6]. The main treatment option in the final stage of this degenerative disease is total knee replacement (TKR) [6]. In the European Union, knee replacement rates are 130 per 100,000 population, respectively. The mean (Standard Deviation) annual direct costs per patient with KOA in Greece have been estimated at EUR 1245.6 (2239.5) [7]. Further, the mean (Standard Deviation) annual direct costs for each patient for TKR have been estimated at EUR 5400.0 (1148.9) [7]. Regarding indirect costs due to sick leave and informal caregivers, the mean (Standard Deviation) has been estimated at EUR 2453.8 (3208.0) for KOA [7]. Worldwide demographic changes--aging, living longer, and growing more obese--mean that its population will need increased care for KOA. In an already overburdened healthcare system, it will be challenging to meet the increased healthcare demands [8]. Thus, effective preventative and rehabilitation strategies are of great importance to limit the social burden of knee OA in the country [8; 9] and worldwide. KOA is a complex, multifactorial disease resulting from dynamic interactions among many risk factors [10]. Common risk factors for developing KOA include increased BMI, female gender, trauma history in the knee, sedentary life, age, and low educational background [11; 12; 13]. Other factors include genetics (e.g., genes encoded for vitamin D receptor, type 2 collagen, growth differentiation factor 5, insulin-like growth factor 1), diet poor in vitamin D, C, and K, diabetes mellitus, abnormal malalignment of the knee, and quadric weakness [10; 14; 15]. Effective policymaking to limit the social burden of the KOA requires an understanding of the disease as a system where the risk factors that lead to the disease interact. However, considering the existing approaches to elucidate the etiology of KOA, in the majority of cases, certain risk factors have been examined and linearly associated with KOA [12; 14; 16; 17].