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Knee OA is a progressive degenerative disease with multiple risk factors. There are several risk factors affect the occurrence of knee osteoarthritis and the risk of disease progression (Fitzgerald and Oatis, 2004). Risk factors can be classified in two categories; systemic factors and local biomechanical factors (Felson et al., 2000) (Figure 2-3)

Systemic factors Age Sex Ethic characteristics Bone density Estrogen replacement therapy (in post- menopausal women) Nutrition factors Genetics

Other systemic factors

Local biomechanical factors Obesity Joint injury Joint deformity Sport participation Muscle weakness

Site and severity of osteoarthritis Susceptibility to

osteoarthritis

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The systemic and local biomechanical factors will be explored briefly below:

2.6.1. Systemic factors

a) Age: The prevalence of knee osteoarthritis increases with age (Peat et al., 2001). Osteophytes, cartilage lesion, and joint space narrowing are common in older people (> 50 years-old) (Guermazi et al., 2012). Additionally, the ability to protect cartilage is deceased with age (Payne et al., 2010).

b) Sex: In general, knee OA is more common in women compared to men (Wright, 2008) and uncommon in both gender under 40 years (Silman and Hochberg, 2001). Men under 50 years have a higher prevalence and incidence of knee OA compared to women. Whereas, women over 50 years have a higher prevalence (Felson et al., 1997; Silman and Hochberg, 2001). Women have a greater prevalence of medial joint space narrowing and a higher varus alignment than men (Wise et al., 2012; Kumar et al., 2015). In addition, women are more commonly affected by osteoarthritis than men due to the role of postmenopausal estrogen deficiency increasing the risk of OA and consequence of several biologic changes (Felson et al., 1995 & 1997).

c) Ethnic characteristics: Ethnicity has also been shown to be a risk factor for knee osteoarthritis in African-American patients than in white people (Jordan et al., 1996). In addition, a higher percentage of Chinese women complain of knee osteoarthritis in comparison with white women (Zhang et al., 2001).

d) Genetics: Genes are a strong risk factor for OA; however, not all joints have the same genetic susceptibility (Spector and MacGregor, 2004). Genetics increases the risk of incidence of knee OA after injury (Loughlin, 2003).

e) Oestrogen effect: A reduction in level of oestrogen hormone in post-menopausal women may be accompanied by an increase in the prevalence and incidence of knee OA. Coincidentally, there is greater risk of knee OA in pre-menopausal women as the hormone raises bone mass, increasing the load on the knee cartilage (Nevitt and Felson, 1997; Richette et al., 2003).

f) Antioxidants: The risk of incidence of knee OA may be increased by a reduction in vitamins C and D. Older individuals with low dietary intakes of vitamin C have greater progression of knee OA and associated with knee pain (McAlindon et al., 1996). There is

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also an increased risk of incidence and progression of knee OA with low levels of vitamin D in older women (Parfitt et al., 1982;Raczkiewicz et al., 2015).

g) Bone density: Bone density has an important role in the initiation and progression of knee OA. High bone density increases the risk of knee OA and it is strongly associated with presence of osteophytes (MacGregor et al., 2000). High bone density was associated with an increased progression of knee OA when knee OA already present and characterised by osteophytes (Hannan et al., 1993; Zhang et al., 2000).

2.6.2. Local Biomechanical factors

a) Obesity increases the load being transferred to the knee joint (Felson et al., 2000) where 60- 70% of weight-bearing load is transmitted through the medial tibiofemoral joint in healthy individuals (Felson et al., 2002). A high body mass index (BMI) (over 30 kg/m²) was found to be a risk factor for knee osteoarthritis and progression of the disease (Yusuf et al., 2011). Research has shown that an increase in body weight by two units of BMI, in obese individuals with knee osteoarthritis, may increase the risk of disease progression by 50 % (Felson et al., 1993).

b) Previous joint injury: An anterior cruciate ligament injury and meniscal tears have been shown to increase the incidence of knee OA (Atkins et al., 2004) by altering load distributions within the damaged knee joint during walking (Doherty et al., 1983; Englund et al., 2004).

c) Cultural: It is a possibility that cultures requiring kneeling or squatting activity over a long period, which is very common in some societies such as the Kingdom of Saudi Arabia, increase the risk of knee OA (Frontera et al., 2006).

d) Occupational: occupations which involve lifting or climbing stairs increase the incidence of knee OA and the disease process by increasing the load on the knee joint (Jensen, 2007). Sports persons and young people doing exercises also face the issue of osteoarthritis because these activities require more direct joint impact and joint twisting (Pujari & Alton, 2010). Evidence concluded that highly intensive sports, such as weight-lifting and soccer increase the risk of knee OA (Driban et al., 2015), One of the potential reasons for this is that the cumulative loading on the knee joint is increased (Klussmann et al., 2010).

e) Muscle weakness: Decreasing muscles strength, especially in the quadriceps and gluteus medius muscles (Chang et al., 2005): Slemenda et al. (1998) found that quadriceps muscle

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weakness increases the development of knee OA, and this weakness has been noticed in individuals with knee OA compared to healthy individuals (Messier et al., 1992; Lewek et al., 2004a). Muscle weakness may due to presence of pain during knee joint movement (Felson et al., 1987) lead to reduced ability of muscle around knee joint to absorb forces during movement resulting in greater loads on the knee joint (Selmenda et al., 1998). f) Varus malalignment: The risk of further narrowing of joint space occurs 3 - 4 times more

often with the presence of varus malalignment in individuals with knee OA (Sharma et al., 2001). Therefore, increasing varus malalignment is associated with the progression and development of knee OA (Brouwer et al., 2007).

These risk factors are multi-factorial and cause degenerative changes within the tissues surrounding the knee. When these changes occur, dynamic balance impairments is associated with knee OA.