Evidence from the medical literature suggests that quadriceps weakness may be a potentially modifiable risk factor for incident symptomatic and progressive knee osteoarthritis, although its relative significance seems to be a function of patient gender and malalignment.
By Neil A. Segal, MD, MS, and Natalie A. Glass, MA
Osteoarthritis (OA) of the knee is a leading cause of disability in American adults.1 An estimated 40% of Americans age 60 and older have radiographic knee OA, many of whom experience mobility limitations.2 Characterized by the deterioration of the whole joint, including formation of osteophytes, loss of cartilage, and sclerosis of subchondral bone, knee OA is a complex disease resulting from multiple biochemical and biomechanical factors. Among the biomechanical factors, it has been suggested that quadriceps muscle weakness may contribute to the pathogenesis of this disease.
Lower limb muscles are important contributors to knee joint loading3 and provide stability to the tibiofemoral joint during locomotion.4 Consequently, some have proposed that lower limb muscles may help to prevent changes in loading at the knee joint that could be associated with incident and progressive knee OA.3,5,6 Among lower limb muscles, the quadriceps muscle is a primary contributor to knee joint stability. Weak quadriceps muscles may fatigue easily, leading to poor neuromuscular control that could allow pathological movement at the joint. Weakness may also reduce shock absorption, leading to abnormal loading of the knee joint. Providing support for this line of reasoning are data from animal models that have shown quadriceps dysfunction may precede degenerative changes.3
In contrast, high quadriceps strength, applied abnormally, could create forces detrimental to the knee joint. Sharma and colleagues found that greater quadriceps strength did not protect against joint space narrowing and, in individuals with malaligned or lax knees, actually increased risk for knee OA progression.7 This finding may have been due to the fact that with malalignment or laxity at the knee joint, load distribution is shifted, and forces that may be helpful when acting at a normal location in the knee joint become harmful when acting at an abnormal location. This possibility is supported by findings that both malalignment and laxity have been shown to increase risk of progression of knee OA.8,9 Another study that suggested a harmful effect of higher quadriceps strength was a randomized trial of a strength-training intervention compared with a range of motion (ROM) intervention. In that study, individuals without radiographic knee OA at the start of the study who were randomized to the strength training intervention were more likely than those in the ROM group to demonstrate accelerated joint space narrowing at 30 months.10 However, it is unclear whether insufficient strength training or higher strength led to excessive joint space narrowing.
Signs of weakness
Despite these two studies in which higher strength was associated with risk, it is more widely accepted that quadriceps muscle weakness may be involved in the pathogenesis of knee OA. Recommendations for quadriceps strengthening are included in clinical guidelines for the management of knee OA.11 Additionally, numerous cross-sectional studies have established the presence of quadriceps muscle weakness in individuals who have knee OA.12-16 Lower quadriceps strength has also been found in people with higher Kellgren-Lawrence (K-L) grades of radiographic severity and with cartilage thinning seen on magnetic resonance imaging (MRI).17
The presence of quadriceps muscle weakness in those with knee OA may be due to pain-inhibition or disuse in those who avoid painful activities and may be out of proportion to loss of muscle mass. Ikeda and colleagues conducted a cross-sectional study of 30- and 60-year-old women with and without knee OA and found smaller quadriceps muscle cross-sectional areas in older women than in younger women, and among older women found an average 12% smaller cross-sectional area of the quadriceps in those with knee OA.18 Similarly, another study found lesser lean mass in the lower limbs of women with knee OA compared with age-matched controls.19 Furthermore, there is evidence for a discrepancy between muscle strength and mass. In the Health ABC study, knee extensor strength declined with age at a higher rate than decline in muscle mass.20 Additionally, in an animal model of knee OA, Herzog et al showed that injections of Botox into the quadriceps of rabbits reduced strength by 60% to 80% but decreased mass by only 37%.3
The inconsistency between loss of muscle strength and mass could be explained by neuromuscular changes that occur in conjunction with knee OA, such as damage to articular mechanoreceptors or inhibition of muscle activation. Several,14,21 but not all,12 investigations have linked muscle activation impairments with knee OA. One small study found that although adults with symptomatic knee OA had no significant difference in central activation ratio (CAR), a measure of voluntary activation, 50% were unable to fully activate their quadriceps muscles, in comparison with 25% of control subjects.12 Hurley et al found that quadriceps maximum voluntary activation, strength and proprioceptive acuity were impaired in people with knee OA.14 Similarly, in a study of those with severe radiographic knee OA (K-L grade 4), quadriceps strength, CAR and lean mass cross-sectional area were significantly lower in limbs with knee OA than in contralateral limbs.22 Importantly, because lean mass explained 41% of the variance in strength in the limb without OA and only 27% of the variance in the limb with OA, these results suggested that activation impairment may be more important than muscle mass in determining quadriceps strength in the context of knee OA. However, this effect may not be apparent in knees with less severe OA.23 Taken together, current evidence supports that activation failure explains a portion of quadriceps muscle weakness found in people with knee OA.
Although weakness can be functionally significant, from a prognostic perspective, it is more important to understand whether quadriceps strength, a modifiable factor, may contribute to the risk of developing knee OA. There is some indirect evidence that weakness of the quadriceps muscle may occur prior to the development of knee OA. A cross-sectional study found lower quadriceps strength relative to body weight in women with radiographic knee OA,15 and because this relationship was present in those without pain or muscle atrophy, the authors suggested that reduced quadriceps strength may precede development of knee OA.15 These investigators later evaluated this relationship longitudinally over approximately two and a half years and reported that reduced quadriceps strength relative to body weight or lower limb muscle mass was present before the development of incident radiographic knee OA in women but not in men.24
These results were confirmed by Hootman et al in a longitudinal study with a mean follow-up duration of 14.4 years.25 In 3,081 individuals, greater quadriceps strength at baseline was associated with a 55% to 64% reduced risk of self-report of either hip or knee OA in women; a similar but non-significant trend was seen in men. In another study, a more functionally-relevant indicator of quadriceps strength (maximum number of one-legged rises) was found to predict development of incident radiographic knee OA five years later in 94 men and women aged 35 to 54 with chronic knee pain after adjustment for age, BMI, sex, and baseline pain.26 However, in this study, 33 out of 41 cases of incident radiographic knee OA occurred in knees that increased from K-L grade 0 to 1, a definition of incident knee OA that differed from other studies. Taken together, these studies seem to support a relationship between quadriceps weakness and development of incident radiographic knee OA.
However, the largest longitudinal study of strength and radiographic knee OA to date showed that, after controlling for age, bone mineral density, BMI, physical activity, injury and surgery, higher quadriceps strength did not protect against the development of incident radiographic knee OA two and a half years later.27 The main differences between this and the earlier longitudinal investigations reported by Slemanda and Hootman related to (1) the way in which strength was reported, (2) the use of radiographs rather than self-report of a diagnosis and (3) whether or not there was an adjustment for pain.
In the earlier longitudinal investigations, strength was reported per body weight. Adjusting strength in this way assumes a linear ratio between strength and body size where, for example, a doubling of body size would necessitate a doubling of strength to maintain a normal ratio. Since strength does not increase linearly with mass, individuals with higher body mass would appear to have reduced quadriceps strength if a 1:1 ratio were assumed. Adjusting strength for weight may have had an affect on the results of the study by Slemenda, in which weights of women with knee OA were greater than those of women without knee OA (81.2 ± 16.9 kg vs 66.1 ± 10.7 kg). The magnitude of the between-group difference in body size was smaller in the Hootman study of self-reported knee OA. In the recent report,27 strength was scaled to BMI without this assumption.
The significance of symptoms
Despite finding that quadriceps strength did not protect against incident radiographic knee OA, the more recent longitudinal study did find that higher quadriceps strength protected against incident symptomatic knee OA (the combination of radiographic knee OA with daily symptoms) in women to a greater extent than in men, thus providing evidence for a longitudinal relationship between quadriceps strength and knee OA. This may be consistent with the results of Hootman et al in that the self-reported outcome used in that study could be more indicative of symptomatic rather than radiographic OA.
Until recently, there was little evidence for a relationship between quadriceps strength and risk for progression of knee OA. In the continuation of the study of Slemenda et al with an average follow-up duration of two and a half years, baseline lower limb lean mass and quadriceps strength per weight did not differ between women with and without radiographic progression of knee OA (increase in K-L grade).28 However, this study did find that baseline strength was 9% lower in women with progression, though this finding was not significant—possibly indicating a sample size limitation of the study. Similarly, another longitudinal study also did not find that quadriceps strength protected against radiographic progression, defined as an increase in joint space narrowing three years later (a proxy for cartilage thinning) after adjustment for age, BMI, knee OA severity, and physical activity.7
Even differences in the way in which progression was measured or use of different indicators of strength in other studies have still resulted in similar findings. For example, Thorstensson et al, utilizing a one-legged rise test as a measure of lower extremity strength, also reported that strength did not predict progression of radiographic knee OA five years later.26 Similarly, in a randomized trial, strength training did not slow the progression of joint space narrowing over 30 months after adjustment for age, BMI, sex, and baseline pain.10 In contrast, Amin and colleagues, using MRI to evaluate cartilage loss, showed that quadriceps strength did not predict tibiofemoral cartilage loss two and a half years later in older adults with radiographic knee OA and frequent symptoms at baseline.29 However, they did find that greater strength protected against lateral patellofemoral cartilage loss.
The largest longitudinal study to date found that in women, higher baseline quadriceps strength offered significant protection against knee OA progression after adjustment for age, BMI, history of lower limb injury or surgery, lower limb mechanical alignment, and physical activity level.30 The study involved 2,182 men and women aged 50 to 79 years, and defined the radiographic worsening of knee OA as an increase in tibiofemoral joint space narrowing 30 months later. Prior studies may not have found a relationship due to their smaller sample sizes28,29 or use of a less sensitive indicator of knee joint worsening.26 Thus, while the majority of studies to date have not supported a relationship between quadriceps strength and knee OA progression, recent evidence suggests a relationship may exist in women.
A potential reason why quadriceps strength confers protection against incident symptomatic as well as progressive worsening knee OA in women only may relate to strength capacity being closer to a threshold for risk.31,32 Men have greater quadriceps strength than women and this may provide greater reserve, so that even with some weakening, the degree of weakness may be insufficient to constitute a risk for these OA-related outcomes. In contrast, women typically have less than 60% the quadriceps strength of men, despite no significant difference in BMI.30,33 Therefore, if a threshold for minimum strength to protect the knee joint exists, women would be closer than men to this threshold, and further weakness could compromise the ability to protect the knee joint.
Knee osteoarthritis is a complex disorder with multiple pathogenic mechanisms. The quadriceps muscles act in concert with other lower limb muscles and ligaments to provide knee joint stability. However, until recently, there was insufficient evidence regarding whether quadriceps strength conferred protection against knee OA. Recent results suggest that the effects of quadriceps strength on knee OA risk are modified by sex and by the presence of malalignment or laxity. In addition, the effect of strength differs depending on the outcome studied (incident vs progressive radiographic vs symptomatic knee OA).
In women, quadriceps strength may potentially be a modifiable risk factor for incident symptomatic and progressive knee OA. Reasons for apparent differences between men and women in the role of quadriceps strength may be related to biomechanical and neuromuscular factors. Studies in young adults have shown that women have lower quadriceps strength, greater knee joint laxity,34 and less joint stiffness than men.35,36 Thus women, who have weaker quadriceps than men, may be closer to a threshold for risk.32,37
While at this time there is no evidence that quadriceps strength training can reduce the risk for incident or progressive knee OA, strengthening exercises have been shown to reduce pain and improve physical function in individuals with knee OA.38 Thus, additional interventional studies are needed to identify whether there are exercise regimens that can reduce risk for developing knee OA and protect against functional loss in those who have knee OA.
Neil Segal, MD, MS, is an associate professor in the department of orthopaedics and rehabilitation at The University of Iowa and the director of the Clinical Osteoarthritis Research Program. Natalie Glass, MA, is a doctoral student in the department of epidemiology in The University of Iowa College of Public Health.
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