Difference in Knee Joint Structure and Lower Extremity Functioning Among People with Varying Severity of Knee Osteoarthritis: A Cross-Sectional Study

Abstract

Osteoarthritis (OA) is a highly prevalent musculoskeletal condition. It is reported that knee OA progressively affects lower-extremity functioning. Evidence is lacking on when there is a substantial decline in function and whether this trend differs between males and females and disease severity. This study aimed to examine influence of gender and increasing grade of knee OA on lower-extremity function. Following Institutional Ethical Committee approval and signed-informed consent, 115 participants (57-males, 58-females), aged 40–65 years, with diagnosed knee OA (grade 1–4) were recruited. Lower-extremity function was studied using reliable and valid outcome variables such as muscle strength-endurance, joint motion, ground-level activity exposure and physical activity. The medial knee joint space width (JSW) decreased by 56.7%(males) and 49.2%(females) from grades 1 to 2 and by 29.6%(males) and 47.8%(females) from grades 3 to 4. Lower-extremity muscle strength and mobility measured by 30-second-deep-squat test declined by 62%(males) and 40.4%(females) from grades 1 to 2 and by 94.4%(males) and 60.9%(females) from grades 3 to 4. Lower-extremity muscle endurance measured by 30-second-chair-sit-to-stand test declined by 8.3%(males) and 7.1%(females) from grades 1 to 2 and by 31.6%(males) and 85.7%(females) from grades 3 to 4. Physical function decreased by 0.3%(males) and 2.3%(females) from grades 1 to 2 and by 22.7%(males) and 32.0%(females) from grades 3 to 4. Physical activity decreased by 27.6%(males) and 28.6%(females) from grades 1 to 2 and by 53.1%(males) and 60.7%(females) from grades 3 to 4. A substantial decline was observed from grades 3 to 4, when both males and females presented considerable reductions in lower-extremity function.

Introduction

Osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders worldwide.1 Approximately 3.8% of the world’s population, or 277 million individuals, have symptomatic knee OA, making it the most common form of arthritis.2

Knee OA affects structure of the knee joint and function of the lower-extremity.3,4 The pathology of OA affects the entire joint, leading to focal and progressive hyaline articular cartilage loss and bony sclerosis. Initial changes are detected on conventional radiographs as joint space narrowing, particularly in the medial compartment.5,3 These changes contribute to the functional impairments observed in individuals with knee OA, such as reduced range of motion and diminished muscle strength and endurance.3 The knee joint structure and lower-extremity function is known to deteriorate with severity of knee OA.6,3 Knee OA severely impacts daily functioning due to pain, reduced mobility, and joint instability, making activities like walking, climbing stairs, and standing challenging. Chronic pain and stiffness related to knee OA hinders daily activities, reduces overall endurance, affects occupational activities and social life.7

Previous studies demonstrated that the functional status of individuals with knee OA deteriorates as the severity of the condition increases.8,9 Functional assessment of patients with knee OA has been assessed using patient-reported outcome measures and performance-based tests. Self-reported questionnaires reported impact of knee OA on quality of life, mobility, pain, and daily activities.10 Patient-reported tools reported pain, stiffness, and physical functioning limitations associated with knee OA, offering subjective insights into daily living impacts. Performance-based measures like the Timed Up and Go (TUG) Test, Six-Minute Walk Test, and stair tests provided objective data on impact of knee OA on mobility, balance, and endurance.11

Reduced muscle strength and endurance was reported as the primary determinant of diminished performance-based physical functioning, as evidenced by poor results on tests such as the 10-m walk test, TUG test, and stair climbing. Limited knee flexion range of motion further contributed to decreased mobility and daily function.12 Pain and physical limitations such as reduced knee range of motion and stiffness; have been shown to limit activity and participation.9 Activities affected vary with disease severity, and individual differences such as genetic predisposition, activity level, and overall health make it challenging to establish a uniform threshold. Personal factors like age, sex, obesity and quality of life further influence the severity of symptoms, with older age and lower quality of life being associated with more significant pain and functional limitations.8 Performance-based tests and self-reported measures, reported moderate to strong correlations with the severity of OA, suggesting that as the condition progresses, physical function diminishes.8,9

While it is widely reported that knee OA progressively affects lower-extremity functioning from early to advanced stages, evidence is lacking on the stage at which there is a substantial decline in lower-extremity function and whether this trend differs between males and females. A community-based survey revealed that individuals with knee OA typically sought help only when their symptoms interfered with daily activities considerably.1

Hence the purpose of this study was to examine the trend of lower-extremity functional decline as knee OA progresses through its advanced stages. The findings of the study will help to plan early restorative interventions for the individuals, which can potentially slow the progression of functional decline and enhance overall patient outcomes and functional independence. Ongoing research combining subjective reports and objective measurements will add to improve the understanding on how knee OA affects daily functioning at different stages of degeneration. Therefore, the present study was designed to examine the influence of gender and increasing grade of severity of knee OA on lower-extremity function.

Methods

Participants

The study was commenced following approval from the Institutional Ethical Committee (Reference no. MGM/DCH/IEC/173/2023, MGM Dental College and Hospital, Navi Mumbai, India), Head of Departments, and authorities and registration of the study with Clinical Trails Registry-India (CTRI/2024/03/064323). The study was conducted in compliance with the principles of the Declaration of Helsinki and ethical standards of the International Journal of Exercise Science.13

A priori power analysis conducted with G*POWER 3.1 determined that 115 participants were required in the current study for a power of 0.95, α= 0.05 with a correlation coefficient (ρ) as 0.3 and WOMAC physical function score as the variable.14 Participants were informed about the study protocol and signed written informed consent was obtained.

Participants were recruited from the Orthopaedic and Physiotherapy outpatient department of Tertiary care Hospital in Navi Mumbai and residential areas of Mumbai and Navi Mumbai. Males and females in the age group 40–65 years with diagnosed unilateral and bilateral knee OA were recruited for the study. Subjects with known meniscal or ligament injury, deformity, lower-limb fractures (in past 1 year), other degenerative and autoimmune disorders such as rheumatoid arthritis, sero-negative arthritis, individuals with acute exacerbation of symptoms with a numerical rating pain scale of ≥6/10 and presence of warmth, lumbar spondylosis and low back pain, arthropathic psoriasis, people with uncontrolled hypertension and resting blood pressure >150/90mmhg, subjects with cognitive issues that prevented comprehension of instructions were excluded.

Protocol

Demographic information included age (years), body height (cms), body weight (kgs), occupation and Body Mass Index (Kg/m²). Habitual physical activity level in the past one month was recorded using Global Physical Activity Questionnaire (GPAQ) which is a valid and reliable questionnaire to estimate an individual’s habitual physical activity in 3 domains (work, transport and leisure time).15 The tool enables quantification of physical activities and reported as MET min/week (Metabolic Equivalent of Task per Week). Participants were screened using Western Ontario and McMaster Universities Arthritis Index (WOMAC) to measure physical function, pain and stiffness.16 The daily ground-level activity of the participants was recorded using a validated MGM Ground Level Activity Exposure Questionnaire (GLAE) (Cronbach’s alpha for reliability: 0.89).17 The 30-second chair sit-to-stand test and 30-second deep-squat test were performed to assess lower-extremity muscle strength-endurance and lower-extremity mobility.17,18 Participants were made comfortable and adequate rest intervals were given in between the tests.

30-second deep-squat test: Participants were instructed to stand with feet placed shoulder width apart and hands outstretched in front. Participants were required to perform complete deep squat and stand repetitively for 30 seconds at his/her own pace trying to perform maximum number of repetitions. The total number of repetitions while performing the test were recorded.17 The participants were asked about any difficulty or pain experienced during testing.

30-second chair sit-to-stand test: The test was conducted using a standard chair without arms, with a seat height of 17 inches (43.2 cm), and a timer. The participants began by sitting in the chair with their feet flat on the floor and arms crossed over their chest. They were instructed to stand up and sit down as many times as possible in 30 seconds. After 30 seconds, the total number of successful stands were recorded.18 The participants were asked about any difficulty or pain experienced during testing.

The radiograph images in standing were used to determine radiological sign of joint space width (JSW) in individuals with knee OA. An Anterior-Posterior weight bearing radiographs of both knees were used for calculating joint space width. Medial JSW was measured on digitized software (MicroDicom DICOM Viewer software 2023.1.1).19 The radiograph images were downloaded into Digital Imaging and Communication in Medicine (DICOM) format files with a spatial resolution of 1584 X 2016 pixels (giving a pixel size of 0.01 mm) and 1024 gray levels. Within the region of interest, the outline of the femoral condyle was designated as the upper rim of the joint space. Outlines of anterior and posterior margins of the tibial plateau were drawn similarly to that of the femoral condyle, and the middle line between the two outlines was designated as the lower rim of the joint space. Then, a straight regression line for the lower rim outline was drawn, and their intersections were designated as the inside rims. The medial joint space area (JSA) was determined as the area surrounded by the upper, lower, inside, and outside rims above. The medial JSW was further determined as the minimum vertical distances in the respective JSA.19

Statistical Analysis

Data were analysed using SPSS version 24 (SPSS IBM, New York, USA). Normality of data was determined using Shapiro-Wilk test and descriptive analysis was done. Central tendency and dispersion were measured. A one-way ANOVA was used to analyze the difference between the means of the age, BMI, WOMAC score, medial JSW, GLAE score, GPAQ score, 30-second deepsquat test repetitions, 30-second chair sit-to-stand repetitions with alpha level set at p =0.05 in participants with grade 1 to grade 4 knee OA. Difference was considered significant with at p ≤ 0.05. Size of difference was interpreted as small = 0.2, medium = 0.5, large 0.8 and very large 1.3.20

Results

The results provide valuable insights into the characteristics of individuals with knee OA across different grades, shedding light on various factors such as age, BMI, physical activity levels and lower-extremity functioning. The study involved a total of 115 participants, categorized into four grades based on the severity of knee OA as per Kellgren and Lawrence grading criteria.

Male and female participants with knee OA demonstrated a clear trend between increased age and advancing severity of knee OA from grade 1 to grade 4. The study results demonstrated that females develop knee OA at an earlier age compared to males. There is an increase in BMI with the progression of knee OA grades. The BMI increased from grade 1 to grade 4 in both males and females; however, this increase was statistically significant in males but not in females. The daily ground-level activity exposure revealed reduced activity with increasing severity of knee OA for both genders, though the differences were not statistically significant (Refer table no. 1). Physical activity levels, as measured by the GPAQ, showed a significant decrease with increasing severity of knee OA in males and females. The mean MET mins/week decrease from grade 1 to grade 4. The GPAQ scores demonstrated decrease of 27.6% in males and 28.6% in females in grade 2 as compared to grade 1. Further, the GPAQ score decreased by 33.8% in males and 23.3% in females with grade 3 Knee OA as compared to grade 2 and by 53.1% in males and 60.7% in females with grade 3 Knee OA as compared to grade 4 (refer to Figure 1).

Figure 1.

Line graphs showing comparison between the structural and functional components in individuals across 1 to 4 grades of knee OA-Medial JSW in males and females (A), 30-second deep-squat test performance in males and females (B), 30-second chair sit-to-stand test performance in males and females (C), WOMAC score in males and females (D), GPAQ score in males and females (E). (on y-axis: Kellgren and Lawrence Grades) JSW: Joint space width, WOMAC: Western Ontario and McMaster Universities Arthritis Index, GPAQ: Global Physical Activity Questionnaire

The medial JSW, indicative of cartilage thickness, showed a marked decrease with increasing severity of knee OA in both males and females. In participants with grade 2 knee OA, 56.7% and 49.2 % decrease in medial JSW was noted in males and females respectively as compared to participants with grade 1 knee OA. In participants with grade 3 knee OA, JSW was decreased by 6.9% in males and 28.1% in females, compared to participants with grade 2 knee OA. In participants with grade 4 knee OA, there was a 29.6% decrease in JSW in males and 47.8% decrease in JSW in females, compared to participants with grade 3 knee OA (refer to Figure 1).

The medial JSW, indicative of cartilage thickness, showed a marked decrease with increasing severity of knee OA in both males and females. In participants with grade 2 knee OA, 56.7% and 49.2 % decrease in medial JSW was noted in males and females respectively as compared to participants with grade 1 knee OA. In participants with grade 3 knee OA, JSW was decreased by 6.9% in males and 28.1% in females, compared to participants with grade 2 knee OA. In participants with grade 4 knee OA, there was a 29.6% decrease in JSW in males and 47.8% decrease in JSW in females, compared to participants with grade 3 knee OA (refer to Figure 1).

The 30-second deep-squat test revealed a significant decline in deep squat repetitions with progressing grade of knee OA. In participants with grade 2 knee OA, 62% and 40.4 % decrease in 30-second deep-squat test was observed in males and females respectively as compared to participants with grade 1 knee OA. In participants with grade 3 knee OA, 30-second deep-squat test was decreased by 5.3% in males and 17.9% in females, compared to participants with grade 2 knee OA. In participants with grade 4 knee OA, there was a 94.4% decrease in 30-second deep-squat test in males and 60.9% decrease in 30-second deep-squat test in females, compared to participants with grade 3 knee OA (refer to Figure 1). The 30-second deep-squat test repetitions decreased by 16.7% in grade 1, 60% in grade 2, 55.6% in grade 3 and by 100% in grade 4 knee OA patients as compared to age matched healthy males. The 30-second deep-squat test repetitions decreased by 50% in grade 1, 75% in grade 2, 80% in grade 3 and by 90% in grade 4 knee OA patients as compared to age matched healthy females.17

The number of repetitions in the 30-seconds chair sit-to-stand test also decreased with greater severity of knee OA in males and females. The 30-second chair sit-to-stand test revealed a decline of 8.3% in males and 7.1% in females in grade 2 compared to grade 1, 2.6% in males and 0% in females in grade 3 compared to grade 2 whereas a decline of 31.6% in males and 85.7% in females in grade 4 compared to grade 3 (refer to Figure 1). In males, 30-second chair sit-to-stand test repetitions decreased by 46.7% in grade 1, 33.4% in grade 2 and grade 3, and by 50% in grade 4 knee OA patients compared to age matched healthy controls. In females, 30-second chair sit-to-stand test repetitions decreased by 50% in grade 1, 53.4% in grade 2, 41.7% in grade 3 and by 66.7% in grade 4 knee OA patients compared to age matched healthy controls.21,22

WOMAC scores, which assess pain, stiffness, and functional limitations, increased with the severity of knee OA in males and females. Higher WOMAC scores in more severe OA grades demonstrate the worsening of symptoms. The WOMAC scores demonstrated minimal increase of 0.3% and 2.3% in grade 2 as compared to grade 1 in males and females respectively. The WOMAC scores demonstrated increase of 41.9% in males and 11.6% in females in grade 3 as compared to grade 2. It demonstrated increase of 22.7% in males and 32.0% in females in grade 4 as compared to grade 3 (Refer Figure 1). The WOMAC score is 30% in grade 1, 30.1% in grade 2, 42.7% in grade 3 and 52.3% in grade 4 of the total WOMAC score in males. The WOMAC score is 36.8% in grade 1, 37.6% in grade 2, 42% in grade 3 and 55.4% in grade 4 of the total WOMAC score in females. The increase in scores as OA progresses indicates that individuals with advanced stages of the disease experience significantly greater levels of discomfort and functional impairment. The substantial decline in lower-extremity functioning is observed particularly from grades 1 to 2 and from grades 3 to 4 knee OA (refer to Table 2).

Table 2.

Functional performance and Joint characteristics of individuals with knee OA

Variables	Male (n=57)						Female (n=58)
	Grade 1 knee OA (n=14)	Grade 2 knee OA (n=14)	Grade 3 knee OA (n=14)	Grade 4 knee OA (n=13)	p-value (One-way ANOVA) for males	Size of difference	Grade 1 knee OA (n=15)	Grade 2 knee OA (n=15)	Grade 3 knee OA (n=15)	Grade 4 knee OA (n=15)	p-value (One-way ANOVA) for females	Size of difference
Medial joint space width (mm)	6.7 (1.5)	2.9 (1.2)	2.7 (1.5)	1.9 (2.0)	0.000*	0.57	6.3 (1.9)	3.2 (1.7)	2.3 (1.0)	1.2 (0.8)	0.000*	0.64
30 Second deep-squat test repetitions	10.0 (2.4)	3.8 (2.7)	3.6 (3.2)	0.2 (0.4)	0.000*	0.56	4.7 (3.6)	2.8 (1.4)	2.3 (1.5)	0.9 (0.4)	0.008*	0.19
30 Second sit-to-stand test repetitions	8.4 (1.6)	7.7 (1.6)	7.9 (1.7)	5.4 (2.8)	0.002*	0.25	7.0 (2.0)	6.5 (2.8)	6.5 (2.2)	3.5 (1.0)	0.000*	0.30
WOMAC Total Score	28.8 (9.0)	28.9 (14.2)	41.0 (11.9)	50.3 (8.1)	0.000*	0.39	35.3 (6.5)	36.1 (11.8)	40.3 (6.5)	53.2 (4.5)	0.000*	0.33

^*level of significance<0.05, Size of difference (partial eta-squared) interpreted as small = 0.2, medium = 0.5, large 0.8 and very large 1.3) (WOMAC: Western Ontario and McMaster Universities Arthritis Index, GPAQ: Global Physical Activity Questionnaire, MET mins/week: Metabolic Equivalent of Task per Week

Discussion

The study provides an overview of how knee OA affects joint structure and lower-extremity function across different grades of severity in males and females.

Present findings confirm that the severity of knee OA progresses with ageing. With an increase in age a variety of factors such as decrease in cartilage regeneration, reduced synovial fluid viscosity, and weakened musculoskeletal support structures contribute to progression of severity of knee OA.6,23 With respect to gender, it was observed that females were younger than males across similar grades of knee OA, which highlights the influence of gender as a specific risk factor for development of knee OA.24 The progressive knee articular cartilage degeneration impairs the joint’s ability to withstand normal mechanical loads, leading to increased pain and functional limitations.5

In males, a significant relationship between BMI and knee OA severity was observed. Higher BMI increases the mechanical loading in the knee, which can accelerate the degenerative changes of the cartilage and contribute to progression of the disease.25 Higher BMI is often associated with reduced physical activity, which further contribute to joint deterioration.26 Hormonal variations between sexes, particularly estrogen, influences cartilage metabolism and joint health especially in females.27 Females generally having a higher percentage of body fat and a different fat distribution pattern as compared to males. Visceral fat and subcutaneous fat have distinct effects on systemic inflammation and joint health, which may contribute to the observed differences.24,26 The decline in ground-level activity shows the impact of knee OA on functional capacity, suggesting that as the condition worsens, the ability to perform daily tasks involving ground-level activities becomes increasingly compromised. The observed reduction in activity could be attributed to the increasing pain, stiffness, and physical limitations associated with higher OA grades.3

The medial JSW is an indicator of the structural integrity of the knee joint, specifically in the inner compartment.28,29 A decrease in medial JSW implies more advanced OA, likely associated with joint stiffness, reduced flexibility and reduced knee range of motion.6 Therefore, individuals with narrower medial JSW may experience difficulty performing activities such as squat, stair descent, and walking.17 The reduction in joint space observed in advanced OA grades thus highlights the progressive breakdown of cartilage and underscores the mechanical consequences of OA on joint function.28 The greater percentage decline in JSW from grades 1 to 2 in males (56.7%) as compared to females (49.2%) might indicate that they experience a more rapid deterioration in joint space width in the early stages of osteoarthritis. The substantial decline in JSW in grades 3 to 4 in females (47.8%) as compared to males (29.6%) suggests an accelerated progression of joint space narrowing in advanced stages.

A significant decline in performance on functional tests such as the 30-second deep-squat and chair sit-to-stand tests with advancing OA severity reflects on impairments in lower extremity strength and mobility. A decrease in performance may indicate that the structural changes associated with OA, such as cartilage loss, bone spurs, and synovial inflammation, compromise the joint’s ability to perform high flexion movements efficiently.17 The decline in 30-second deep-squat test repetitions was greater in males compared to females which may be due to less involvement in high flexion activities.17

Similarly, the decline in 30-second chair sit-to-stand test repetitions may be attributed to weakened muscle strength, increased joint pain, and reduced proprioceptive feedback, all of which may impair the ability to perform functional tasks that require strength and coordination.30 The greater decline in females in grade 4 as compared to grade 3 compared to the earlier stage and compared to males indicates that the chair sit-to-stand test performance deteriorates significantly as knee OA progresses.

The increase in WOMAC scores with greater OA severity reflects the growing impact of knee OA on pain, discomfort, stiffness, and functional limitations. The increase in WOMAC score in females (32.0%) in grade 4 as compared to grade 3 is more pronounced compared to males (22.7%), indicating that females experience a more severe decline in quality of life and functional ability as knee OA advances to its later stages. Gender differences in WOMAC scores are often attributed to variations in pain perception, physical activity, and disease severity.31,16

The observed decrease in physical activity levels with increasing knee OA severity highlights the broader biomechanical and lifestyle impacts of the disease. Patients demonstrated reduced physical activity which is primarily driven by pain, discomfort during weight-bearing activities, stiffness, fear of joint damage, muscle weakness, and adaptation to a sedentary lifestyle.17,32 This reduction in physical activity can further contribute to muscle weakness, decreased cardiovascular health, and a general decline in physical fitness, which can exacerbate the symptoms of OA and impact overall health.33 For males, the decline in physical activity is substantial throughout, with a more severe drop observed in the later stages. Females also showed a significant reduction in physical activity, with an even more noticeable decrease in advanced stages.

The study examined relationships between knee OA severity, joint structure, and lower-extremity functioning. The substantial point of decline appears to be in the transition from grades 3 to 4, where both males and females experienced significant reductions in joint space width and lower-extremity function such as reduced physical activity levels, muscle strength, endurance, and knee motion with increasing OA severity. In early stages, individuals may experience mild symptoms like occasional stiffness and discomfort, which typically do not significantly affect their ability to perform daily activities. However, as OA progresses to moderate stages, the symptoms become more severe and frequent which interferes considerably with daily activities.6

Addressing functional limitations at an early stage is crucial in improving the quality of life and preventing further deterioration of knee OA. Therefore, the findings of the study strongly suggest the need for early restorative interventions in grades 1 and 2 of knee OA. The interventions need to be multifaceted including therapeutic and ergonomic strategies, nutritional strategies, psychological counselling for addressing the fears that activity worsens OA or kinesiophobia, functional rehabilitation and promotion of physical activity to enhance the overall well-being of affected individuals.9,34,35 As people seek medical consult when they had severely debilitating knee pain which significantly interfered with daily activities, these findings warrant a strong need for patient education in order to seek early treatment. For the interventions to be most effective they should be integrated at the primary level, such as in primary health care centers and within community settings. This approach ensures accessibility and encourages proactive management of knee OA, fostering better health outcomes for affected individuals.36

Table 1.

Demographic characteristics of individuals with knee OA

Variables	Male (n=57)						Female (n=58)
	Grade 1 knee OA (n=14)	Grade 2 knee OA (n=14)	Grade 3 knee OA (n=14)	Grade 4 knee OA (n=13)	p-value (One-way ANOV A) for males	Size of difference	Grade 1 knee OA (n=15)	Grade 2 knee OA (n=15)	Grade 3 knee OA (n=15)	Grade 4 knee OA (n=15)	p-value (One-way ANOV A) for females	Size of difference
Age	46.1 (8.6)	51.6 (8.8)	56.3 (5.0)	61.5 (3.8)	0.000*	0.39	50.6 (7.2)	49.3 (8.1)	55.6 (8.1)	60.4 (4.2)	0.000*	0.28
Body Mass Index (Kg/m2)	23.5 (3.0)	24.8 (1.6)	27.0 (2.4)	27.1 (4.2)	0.005*	0.22	27.0 (3.5)	26.8 (2.8)	27.2 (4.4)	29.1 (3.0)	0.252	0.07
Total Daily Ground Level Activity Exposure (mins)	84.3 (56.5)	83.9 (56.8)	76.4 (53.6)	67.3 (50.9)	0.073	0.05	140.3 (79.6)	124.0 (66.9)	112.7 (74.4)	80.7 (49.8)	1.121	0.05
GPAQ (MET mins/week)	4212.9 (2976.3)	3051.4 (2658.9)	2021.5 (354.9)	1320.0 (398.0)	0.004*	0.23	2588.0 (1496.6)	1848.0 (1761.2)	1417.3 (1376.6)	557.3 (447.9)	0.005*	0.13

^*level of significance<0.05, Size of difference (partial eta-squared) interpreted as small = 0.2, medium = 0.5, large 0.8 and very large 1.3