Correlation of Knee Instability With Alignment And Repetitive Physical Activity In Patients With Knee Osteoarthritis: A Cross-Sectional Study

doi:10.21203/rs.3.rs-686545/v1

Objectives. Malalignment, dynamic knee instability, and repetitive physical activity are considered biomechanical risk factors for knee osteoarthritis (KOA), though the correlations among these factors are poorly understood. The purpose of this study was to elucidate the relationship between knee instability and alignment, and to determine the effects of repetitive physical activity on knee instability in patients with KOA.

Methods. The study subjects were 68 patients with radiographic tibiofemoral KOA and 68 control subjects. Each participant underwent clinical evaluation, muscle strength test, radiography, and knee instability test. Instability was evaluated before and after repetitive stepping exercise using triaxial accelerometer.

Results. Mediolateral acceleration correlated (p<0.01) with two coronal alignments (mechanical axis; HKA and joint line convergent angle; JLCA). Pearson correlation coefficient was small (r=0.23-0.24) before but increased after stepping (r=0.28-0.33). Increased mediolateral acceleration after stepping correlated with JLCA (r=0.37, p<0.001) . There were significant differences in coronal alignments, gait speed, mediolateral acceleration, and accelerations in all directions between the control and KOA groups. Anteroposterior acceleration did not correlate with sagittal knee alignment. Multiple logistic regression analysis identified HKA/JLCA, and increased mediolateral acceleration after stepping as significant diagnostic predictors of KOA.

Conclusion. We found a direct relationship between knee instability and knee alignment or repetitive physical activity. Repetitive stepping activity significantly increased mediolateral acceleration in KOA patients, compared to the control. Stepping increased the correlation between mediolateral acceleration and coronal alignment. In knees with large JLCA, repetitive stepping provided much larger mediolateral instability. Our results suggest that, in addition to JLCA, the increase in mediolateral acceleration after repetitive physical activity, possibly contributes to the development of KOA.

Trial registration

Tan-nan Regional Medical Center TRMC No. 2018-1

Immunology

Rheumatology

Knee joint

knee osteoarthritis

alignment

physical activity

Knee instability

accelerometry

pathogenesis

Malalignment of the knee is a major risk factor for the development and progression of knee osteoarthritis (KOA) (1–3). Evidence suggests that changes in the geometry of the articular surface affect the biomechanical properties of the joint, which can ultimately result in damage of the articular cartilage (4–7). Another pathological factor in KOA is mechanical stress resulting from high physical activity of daily living or occupation (8–12). For example, prolonged or repeated squatting (8, 10, 11) and stressful stair climbing activity are considered risk factors for KOA (8, 9, 12), although a few groups have argued that high physical activity is not associated with the incidence or worsening of KOA (13, 14).

Knee joint laxity and instability are also major factors that contribute to the physical function of the knee joint and risk factors for KOA (15–20). In this regard, varus thrust during walking is considered a risk factor for radiographically-confirmed progression of medial (RKOA) (21, 22), and for the development and worsening of MRI-confirmed medial tibiofemoral lesion (23). Knee thrust is usually diagnosed by physical examination, though Change et al (24) used a motion analysis system to demonstrate a close association in OA patients between knee thrust and peak varus angle and angular velocity. However, only a few studies have examined the direct relationship between knee instability and alignment or physical activity. Kuroyanagi et al (25) used the varus-valgus angle, representing the amount of thrust, and demonstrated its correlation with radiographic alignment. Our group reported an increase in the antero-posterior and mediolateral laxity of the knee after stair climbing in patients with mild KOA (26). However, the knee joint laxity was only measured in that study under static conditions. To our knowledge, there is no information on dynamic knee joint instability during physical activity in RKOA.

Figure 1 illustrates the pathological relationship between the above-mentioned mechanical factors and RKOA. To our knowledge, little is known regarding the correlation of knee instability or alignment with repetitive physical activity. Since early 1990s, several studies applied accelerometry to evaluate the knee joint under dynamic instability conditions (27–31). For example, a significant decrease in the lateral thrust, as measured by accelerometry, was reported in patients with varus OA knees using lateral wedge insole (28). Advanced technological development in accelerometry was applied by Turcot et al (31) to determine tri-axial instability of the tibiofemoral joint.

We hypothesized that significant relationships exist between knee instability or alignment with repetitive physical activity. To test our hypothesis, we determined the relationship between dynamic knee joint instability and coronal/sagittal knee alignment, and the effect of repetitive physical activity on knee instability in patients with RKOA. We used tri-axial accelerometry to evaluate tibiofemoral instability. Repetitive squatting has been reported previously to study the effects of high physical activity on the knee joint (8, 10, 11), however, this form of activity could potentially cause considerable pain in patients with KOA. For this reason, we used stepping exercise in this study as representative high physical activity in daily living. The main purpose of this study was to elucidate the relationship between knee instability and alignment, and to determine the effects of repetitive physical activity on knee instability in patients with RKOA

Subjects

City dwellers aged ≥ 50 years were invited through advertisements to volunteer in this study. Power analysis using G Power 3.1.9 (Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany) estimated participation of at least 64 subjects in order to detect group differences, with two-tailedαof 0.05, power of 80%, and effect size of 0.5. We excluded subjects with patellofemoral malalignment, diagnosed previously with rheumatoid arthritis or severe spinal stenosis, and also subjects who had undergone knee surgery previously, as well as paraplegic subjects and those who could not stand on one leg or climb up/down stairs. All subjects underwent radiological assessment of the knee for KOA using the Kellgren-Lawrence (K/L) scoring system (in this system, grade 0 signifies no OA and grade 4 represents severe OA). Based on the results of radiographic examination, the selected study subjects were 68 participants (34 men and 34 women) with radiographic K/L grade 0–1 (here called the control group), and 68 (34 men and 34 women) with K/L grade 2–4. Only the index knee was selected for analysis in each participant. There were no significant differences in age and side of the knees between the control and OA groups. However, the body mass index (BMI) of the OA group was significantly larger than that of the control (Table 1).

Table 1

Demographic data
	RKOA group (n = 68, rt/lt)	Control group (n = 68, rt/lt)	P value*	Effect size Cohen’ d
K-L grade
0	0	25 (16/9)
1	0	43 (21/22)
2	27 (14/13)	0
3	15 (8/7)	0
4	26 (16/10)	0
Side
right	38	37	0.86
left	30	31
Age, years	69.0 (8.0)	67.1 (8.1)	0.18	0.23
Gender
Males	34	34
Females	34	34
BMI, kg/m²	25.0 (3.0)	23.6 (3.6)	0.02	0.40
Data are mean (SD) or number of subjects.
* by unpaired t-test (continuous variables) or chi-square test (categorical variables)
RKOA: radiographic knee osteoarthritis
K-L: Kellgren and Lawrence, BMI: body mass index

All participants provided written informed consent according to the Declaration of Helsinki. The study protocol was approved by the Ethics Review Committee of Tan-nan Regional Medical Center, Fukui (TRMC 2018-1).

Clinical evaluation

Subjects were asked to fill in the knee injury and osteoarthritis outcome score (KOOS) (32). KOOS assesses five outcomes; pain, symptoms, activity of daily living (ADL), sport and recreational function, and knee-related quality of life. The KOOS meets the basic criteria of outcome measures and is used to evaluate the course of knee injury and treatment outcome (32). Since the study subjects were patients with primary KOA, we evaluated the activities of daily living (KOOS-A), pain (KOOS-P), and OA-related symptoms (KOOS-S).

Assessment of muscle strength

The isokinetic strength of the quadriceps and hamstring muscles was evaluated by the Biodex System Dynamometer (Biodex Medical Systems, NY) at angular speed 60°/sec. Each subject was tested three times and the highest value was chosen for analysis.

Radiography

Standing radiographs of the knee in anteroposterior (AP), lateral, and skyline views were obtained in all participants. Furthermore, all subjects underwent fluoroscopic-assisted, standing AP and full length AP radiographs in a semi-flexed position. The AP radiograph of the knee was obtained with the radiographic beam pointing parallel to the medial tibial plateau. The full length one-leg standing AP radiograph of the leg was used to express the varus valgus alignment of the leg using the mechanical axis; the hip-knee ankle angle (HKA), which represents the angle between the line connecting the center of the femoral head and the center of the tibia plateau and the line connecting the center of the tibia plateau and center of the ankle, (Fig. 2a). The joint line convergent angle (JLCA) (33) was obtained using the one-leg standing AP radiograph. The JLCA represents the angle between the line connecting the most distal point of the medial and lateral femoral condyles and the line connecting the proximal medial and lateral edges of the tibia plateau (Fig. 2b). Using the AP radiographs, the medial slope angle of the tibia plateau (MS) was defined as the angle between the line connecting the proximal medial and lateral edges of the tibia plateau and the line connecting the two points of center of the tibial shaft (7 cm and 12 cm distal to the tibial plateau) (Fig. 2b). Finally, the posterior slope angle of the medial tibial condyle (PS) was measured. It represents the angle between the line connecting the anterior and posterior edges of the medial tibial condyle and the line of the anterior margin of the tibia, distal to the tibial tubercle (Fig. 2c).

Accelerometry

Three small triaxial accelerometric wireless sensors (WAA-006™, Tekscan, MA) were attached to the fibular head, lateral femoral condyle, and lateral side of the leg, with skin tape and 7 cm-wide Velcro band. A pressure sensor (FlexiForce™, Nitta, Japan) was also attached to the heel with skin tape. The subject was instructed to walk on a 10 m flat floor at own comfortable natural speed, then step up and down 20 times on a 20 cm-high stepper, and finally walk on the flat floor. The sampling rate was 1 kHz for accelerometry and 50 Hz for the heel pressure sensor. The data of the femur, tibia and heel pressure sensors were synchronized, and the difference in accelerometry between the femur and the tibia was analyzed (WAA Data Analyzer, ATR-Promotions, Kyoto, Japan). The data were filtered using a Butterworth low-pass filter with a cutoff frequency of 10Hz, and the triaxial acceleration of the femur relative to the tibia was obtained (Fig. 2). The range between the positive peak and the following negative peak was defined as the magnitude of the acceleration. The first 10 acceleration waves starting from the heel were selected and the average values were used for the following analysis.

Statistical analysis

Reproducibility of measurements of accelerometry of the knee joint was tested in 10 KOA patients on two separate days. The average intraclass correlation (ICC) for antero-posterior direction was 0.99 before stepping and 0.93 after stepping. The ICC for mediolateral direction was 0.97 before stepping and 0.86 after stepping and for proximal and distal direction, it was 0.90 before stepping and 0.95 after stepping.

The association between accelerometry and the alignments was analyzed using Pearson’s correlation analysis.

Two-tailed unpaired t-test and multiple logistic regression analysis were used for analysis of the clinical outcome, knee muscle strength, radiographic, gait speed and accelerometric data comparison between the OA and control groups. Effect size as Cohen’s d (34) was calculated to scale and rank the difference in all measures between the two groups.

All statistical analyses were conducted using the EZR software ver. 1.27 (35), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, it is a modified version of R commander designed to add statistical functions frequently used in biostatistics. The level of statistical significance was set at p < 0.05.

All subjects completed the study protocol without additional knee pain.

Mediolateral acceleration correlated significantly (p < 0.01) with two coronal alignments (mechanical axis; HKA and joint line convergent angle; JLCA). The Pearson correlation coefficient was small (r = 0.23–0.24) before stepping, and increased after stepping (r = 0.28–0.33). The increase in mediolateral acceleration after stepping correlated significantly and largely (r = 0.37, p < 0.001) with JLCA.

MS did not correlate with mediolateral acceleration before stepping (bZ) (p = 0.11) and poorly (r= -0.18, p < 0.05) after stepping (aZ).

In the sagittal plane, PS did not correlate with acceleration in the antero-posterior direction; bY, aY, and a-bY (p = 0.92, 0.57, and 0.18 respectively) (Table 2).

Table 2

Relationship between acceleration and alignment in the coronal and sagittal planes.
Parameter 1	Parameter 2	Pearson’s correlation coefficient	95% CI	P value
bZ	HKA	0.24	0.08–0.40	< 0.01
bZ	JLCA	0.23	0.07–0.39	< 0.01
bZ	MS	-0.14	-0.30–0.03	0.11
aZ	HKA	0.28	0.12–0.43	< 0.01
aZ	JLCA	0.33	0.17–0.48	< 0.001
aZ	MS	-0.18	-0.33 - -0.008	< 0.05
a-b Z	HKA	0.22	0.05–0.38	< 0.05
a-b Z	JLCA	0.37	0.21–0.51	< 0.001
a-b Z	MS	-0.16	-0.32- -0.005	0.057
bY	PS	-0.009	-0.18–0.16	0.92
aY	PS	0.05	-0.12–0.22	0.57
a-b Y	PS	0.12	-0.05–0.28	0.18
95%CI: 95% confidence interval, HKA: hip-knee-ankle angle in the coronal plane, MS: medial slope angle of the tibial plateau in the coronal plane, JLCA: joint line convergence angle in the coronal plain, PS: posterior slope angle of the medial tibial plateau in the sagittal plane, bZ, aZ, bY, aY: average acceleration of anteroposterior (Y), and mediolateral (Z) directions before (a) and after (b) stepping.
a-b Z (Y): difference of mediolateral (anteroposterior) acceleration after stepping

All KOOS parameters (KOOS-A, KOOS-P, KOOS-S) and isokinetic muscle strength (quadriceps and hamstring) were significantly lower in the RKOA (p < 0.0001, each), compared with the control subjects. Within the coronal alignments, HKA and JLCA were larger (p < 0001), and MS smaller (p < 0.01) significantly in the RKOA group, but not the sagittal knee alignment (PS) (p = 0.14), compared with the control group (Table 3).

Table 3

Patient-reported outcome measures (KOOS), isokinetic muscle strength, alignment, and accelerometry
	RKOA group n = 68	Control group n = 68	P value	Effect size Cohen’ d
KOOS
Activities of daily living	75.9 (10.6)	88.5 (10.2)	< 0.001	1.22
Pain	69.2 (14.2)	93.1 (9.6)	< 0.001	1.99
Symptoms	66.4 (16.4)	90.1 (12.7)	< 0.001	1.63
Isokinetic knee muscle strength
Quadriceps, Nm/kg	0.78 (0.34)	1.10 (0.31)	< 0.001	0.99
Hamstrings, Nm/kg	0.39 (0.22)	0.64 (0.32)	< 0.001	0.92
Alignment
HKA, °	7.5 (4.4)	3.9 (3.0)	< 0.001	0.98
JLCA, °	3.9 (2.1)	1.2 (0.8)	< 0.001	1.69
MS, °	85.1 (1.9)	86.2 (2.3)	< 0.01	0.50
PS, °	77.5 (1.8)	78.1 (2.9)	0.14	0.26
Walking speed, m/s	0.72 (0.15)	0.85 (0.15)	< 0.001	0.84
Accelerometry
bX, m/s²	0.69 (0.31)	0.61 (0.18)	0.07	0.32
bY, m/s²	0.61 (0.21)	0.56 (0.16)	0.13	0.27
bZ, m/s²	0.54 (0.20)	0.46 (0.12)	< 0.01	0.49
aX, m/s²	0.87 (0.40)	0.71 (0.20)	< 0.01	0.51
aY, m/s²	0.75 (0.28)	0.63 (0.19)	< 0.01	0.50
aZ, m/s²	0.69 (0.26)	0.52 (0.13)	< 0.001	0.83
a-b X, m/s²	0.18 (0.17)	0.10 (0.08)	< 0.01	0.60
a-b Y, m/s²	0.14 (0.13)	0.08 (0.09)	< 0.01	0.54
a-b Z, m/s²	0.14 (0.10)	0.05 (0.05)	< 0.001	1.22
Data are mean and (standard deviation).
RKOA: radiographic knee osteoarthritis, HKA: hip-knee-ankle angle in the coronal plane, MS: medial slope angle of the tibial plateau in the coronal plane, JLCA: joint line convergence angle in the coronal plain, PS: posterior slope angle of the tibial plateau in the sagittal plane, bX, bY, bZ, aX, aY, aZ,: average acceleration of proximal-distal (X), anteroposterior (Y), and mediolateral (Z) directions before (b) and after (a) stepping. a-b X, a-b Y, a-b Z: difference of acceleration after stepping in X, Y, Z directions

The walking speed of the OA group was significantly slower (p < 0.001) than that of the control. Before stepping, acceleration of the OA group was significantly larger than the control group in only mediolateral direction (bZ). However, accelerations after stepping and the change in acceleration after stepping were significantly larger in both proximal-distal (aX and a-bX) and anteroposterior directions (aY and a-bY), as well as mediolateral direction (aZ and a-bZ) (p < 0.01). (Table 3).

Multiple logistic regression analysis was performed using RKOA (KL2-4) as the outcome with six independent variables (BMI, KOOS-P, quadriceps muscle strength, walking speed, a-b Z (or bZ), and JLCA (HKA or MS)). The following six models were used with these variables: a-b Z and JLCA (model 1), a-b Z and HKA (model 2), a-b Z and MS (model 3), bZ and JLCA (model 4), bZ and HKA (model 5), and bZ and MS (model 6). After accounting for all the variables, both JLCA and HKA significantly (p < 0.05) affected the diagnosis of RKOA (models 1, 2, 4, 5), while MS did not (models 3 and 6). In addition, a-b Z significantly (p < 0.001) discriminated RKOA from non-OA (models 1–3), while bZ did not (models 4–6) (Table 4).

Table 4

Results of logistic regression analysis with the stepwise procedure for the diagnosis of radiographic knee osteoarthritis
Variables	Odds ratio	95% CI	P value
Model 1
KOOS-pain	0.86	0.81–0.93	< 0.001
JLCA, °	4.77	2.04–11.2	< 0.001
a-b Z, 10m/s²	8.11	2.36–2.79	< 0.001
Model 2
KOOS-pain	0.86	0.81–0.97	< 0.001
HKA, °	1.38	1.07–1.78	< 0.05
a-b Z, 10m/s²	8.09	2.65– 24.7	< 0.001
Model 3
KOOS-pain	0.86	0.81–0.91	< 0.001
a-b Z, 10m/s²	8.78	3.01–25.6	< 0.001
Model 4
KOOS-pain	0.86	0.83–0.93	< 0.001
JLCA, °	4.83	2.35–9.93	< 0.001
Model 5
KOOS-pain	0.87	0.83–0.92	< 0.001
HKA, °	1.41	1.14–1.74	< 0.01
Model 6
KOOS-pain	0.87	0.84–0.91	< 0.001
95% CI: 95% confidence interval, KOOS: Knee Injury and Osteoarthritis Outcome Score, HKA: hip-knee-ankle angle in the coronal plane, JLCA: joint line convergence angle in the coronal plain, a-b Z: difference of acceleration after stepping in mediolateral direction

In this study, we measured dynamic knee instability using tri-axial accelerometer before and after repetitive stepping activity and demonstrated significant relationship between mediolateral knee instability and coronal alignment of the knee.

In the coronal plane, the load distribution across the femorotibial joint is estimated predominantly in knees with normal alignment. Knees with varus deformity receive the total load almost entirely on the medial compartment (36). The mechanical stress concentrated on the medial compartment produces high adduction moment of the knee and opening of the lateral side of the joint, which is described as varus thrust (37). The degree of lateral opening is indicated directly by JLCA and indirectly by HKA. Accordingly, mediolateral acceleration, which quantitatively represents varus thrust, likely correlates significantly with HKA and JLCA.

Maeyama and coworkers (38) measured three directions of acceleration. They reported that the overall magnitude of acceleration of the dysplastic hip was significantly larger than that of the contralateral normal hip. They found a significantly high correlation between radiographic center-edge angle and the overall magnitude of acceleration (r=- 0.73, p < 0.0001). The hip joint has ball and socket anatomy, which is supported by many muscles multi-directionally. Thus, instability related to the bony structure is often strongly responsible for dynamic joint instability. On the other hand, the anatomical morphology of the knee joint is more complex. In addition, the joint is supported by not only the surrounding muscles, but also by a series of ligaments, supporting structures and soft tissues. Therefore, any instability associated with the bony structures, described as knee alignment, may be less responsible for dynamic knee instability.

The JLCA has been used recently to describe the magnitude of medial and lateral coronal soft tissue laxity in tibial osteotomy for KOA (39). Although the JLCA reflects the effect of soft tissue laxity, and it varies greatly in subjects with KOA (40), its significance in the understanding of the pathogenesis of KOA is unclear. In the present study, JLCA correlated significantly with the a-b Z, indicating JLCA may be a valuable marker to estimate mediolateral acceleration after stepping activity. In addition, multiple logistic regression analysis identified it as a marker for the radiographic diagnosis of KOA. Therefore, JLCA could be a potentially useful radiographic index for evaluation of KOA pathology.

The MS/PS is the anatomical angle of the tibia plateau that reflects joint configuration. Driban et al (6) showed that a greater coronal tibial slope significantly affected the load distribution, and it was associated with increased risk of incident accelerated KOA, particularly among knees with malalignment. On the other hand, using a musculoskeletal model for healthy adults, Van Rossom et al (7) demonstrated that small changes in coronal tibial slope had a less pronounced effect on the load distribution, though coronal plane malalignment significantly affected it. In the present study, although the MS was significantly smaller (proximal tibial surface inclines more medially) in patients with RKOA compared to that of the control, it was not helpful in the diagnosis of KOA even after adjustment for other variables. Furthermore, we did not find the significant difference of PS between the control and RKOA groups, and the PS did not correlate with acceleration in the antero-posterior direction. In this regard, Van Rossom et al (7) reported that transverse plane malalignment only minimally affected the load distribution. Further research is needed to determine how individual joint geometry influences knee joint instability and the risk of KOA.

Our results also showed significantly larger mediolateral acceleration in patients with RKOA, compared with the control. However, the difference became insignificant after adjustment for all other variables.

Turcot et al (31) demonstrated significant high acceleration in anteroposterior and mediolateral directions in patients with KOA compared to the control, and concluded that the accelerometric method used in their study could discriminate between asymptomatic subjects and patients with medial KOA. They also indicated that the difference between their results and those reported by Lafortune et al (27) were probably related to differences in gait velocity, location of the accelerometer, and sensor fixation method. Walking speed is a major factor affecting gait (41). However, we instructed our subjects to walk at their own natural pace so as to conduct the test under similar daily activity. In fact, our RKOA patients walked significantly slower than the control (p < 0.0001, Cohen’d = 0.84). With respect to the placement of the accelerometer, the femoral sensor was attached on the lateral epicondyle of the femur, while the tibial sensor was fixed to the fibular head. These sites were easy to locate on the skin. In addition, accelerometer should be placed on the lateral aspect of the leg for more accurate measurement (42). In our study, we measured body synchronous movements through the use of several sensors with good reproducibility of the obtained relative femorotibial acceleration. Care should also be taken to reduce artifacts produced by the sensor-skin mounting technique. In this regard, the use of exoskeleton may be advantageous relative to skin tape, although we used skin tape and firmly rapped wide Velcro band when placing the sensors on the skin.

After adjustment for all variables, the only significant difference in acceleration between RKOA patients and the control group was the average increase in mediolateral acceleration after repetitive stepping. Mediolateral instability occurred much more in patients with RKOA after 20 stepping activities on the 20cm-high stepper.

Luepongsak et al (43) reported that among several daily living activities, descending stairs was associated with the highest forces across the knees and hips. Sahlström et al (44) applied gait analysis and demonstrated that climbing stairs is associated with a significant increase in knee moment in healthy subjects. Another study showed that malalignment and overweight can increase mechanical stress on the knee joint (45). In addition to our previous study in patients with KOA (26), a few studies also reported that certain physical exercises can induce knee joint laxity in athletes (46–48).

With regard to the soft tissues around the knee joint, previous studies demonstrated a strong relationship between decreased stiffness and reduced strength of the medial collateral ligament under cyclic loading (46). Others reported greater co-contraction of the medial muscle in response to medial knee joint laxity in patients with medial KOA (49). In our study, isokinetic knee muscle strength was significantly lower in the OA group compared to the control subjects. In this regard, muscle weakness is a known risk factor for KOA (50–51). In the elderly, repetitive physical exercise, such as stepping exercise, even for a relatively short period of time, may cause muscle fatigue (52) and reduce stiffness of the collateral ligament (46), as the knee becomes more unstable.

In this study, JLCA significantly correlated with medio-lateral acceleration after repetitive stepping (aZ and a-b Z). This suggests that knees with large JLCA are potentially susceptible to the development or progression of KOA. Our study also demonstrated a significant increase in mediolateral acceleration in KOA patients after repetitive stepping, compared with non-OA subjects. In addition, a-b Z was a significant independent marker of KOA, suggesting that such activities during daily living are probably associated with the pathogenesis of KOA.

Our study has certain limitations. With regard to the stepping protocol, we set the height of the step and frequency of stepping up and down so that all subjects were able to complete the test without suffering further knee pain. The results would have been different if the exercise level had been harder or tailored to the daily activity of the individual patient. Nevertheless, the results showed significantly larger post-exercise increase in mediolateral acceleration in patients with RKOA relative to the non-OA control, suggesting repetitive physical exercise may play a role in mechanical pathology for KOA. Another limitation of the study was the cross-sectional design. Further longitudinal studies are needed to determine whether coronal alignment abnormality and increased acceleration after repetitive stepping are risk factors for the development or progression of KOA.

In summary, we found a direct relationship between knee instability and knee alignment or repetitive physical activity. Repetitive stepping activity resulted in a significant increase in mediolateral acceleration in RKOA patients, compared to the control. The correlation between mediolateral acceleration and coronal alignment increased after stepping compared with before stepping. In knees with large JLCA, repetitive stepping activity provided much larger mediolateral instability. Our results suggest that increases in mediolateral acceleration after repetitive physical activity as well as JLCA seem to contribute to the pathogenesis of KOA.

a-b X (Y or Z): difference in acceleration after stepping in proximal-distal (antero-posterior or medio-lateral) direction

b(a)X (Y or Z): acceleration before (after) stepping in proximal-distal (antero-posterior or medio-lateral) direction

HKA: hip-knee-ankle angle

JLCA: joint line convergence angle

KOA: knee osteoarthritis

KOOS: the knee injury and osteoarthritis outcome score

MS: medial slope angle of the proximal tibia

PS: posterior slope angle of the proximal tibia

RKOA: radiographic knee osteoarthritis

Ethics approval and consent to participate

All participants provided written informed consent. This study was approved by the Human Ethics Committee of Tan-nan Regional Medical Center (protocol #2018-1).

Consent for publication

Consent for publication was obtained from all participants.

Availability of data and materials

The datasets used and analyzed in this study are available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Funding

This study was conducted without specific financial support from any public, commercial or not-for-profit organizations.

Authors’ contributions

Affiliations

Department of Orthopedic Surgery, Tan-nan Regional Medical Center, Fukui, Japan. Makoto Wada & Yusuke Yamamoto
Department of Orthopedic Surgery, University of Fukui, Fukui, Japan. Tsuyoshi Miyazaki & Takumi Sakamoto.
Sensor products division, ATR-Promotions Inc., Kyoto, Japan. Takahiro Adachi

MW measured, analyzed, interpreted the data, and wrote the manuscript. TM and TS contributed to the study design. YY analyzed and interpreted the data. TA contributed the data acquisition and graphical presentation.

Acknowledgments

We gratefully thank Seiichiro Shimada, The University of Fukui, for the statistical advice.

Conflict of interest

All authors declare no conflict of interest.

Brouwer GM, van Tol AW, Bergink AP, et al. Association between valgus and varus alignment and the development and progression and radiographic osteoarthritis of the knee. Arthritis Rheum 2007; 56:1204-11.
Sharma L, Song J, Dunlop D, et al. Varus and valgus alignment and incident and progressive knee osteoarthritis. Ann Rheum Dis 2010;69:1940-5.
Hayashi D, Englund M, Roemer FW, et al. Knee malalignment is associated with an increased risk for incident and enlarging bone marrow lesions in the more loaded compartments: The MOST study. Osteoarthritis Cartilage 2012; 20: 1227-33.
Hashemi J, Chandrasheker N, Gill B, et al: The geometry of the tibial plateau and its influence on the biomechanics of the tibiofemoral joint. J Bone Joint Surg Am 2008; 90: 2724-2734.
Bredbenner TL, Eliason TD, Potter RS, et al: Statistical shape modeling describes variation in tibia and femur surface geometry between control and incidence groups from the osteoarthritis initiative database. J Biomech 2010; 43: 1780-1786.
Driban JB, Stout AC, Duryea J, et al. Coronal tibial slope is associated with accelerated knee osteoarthritis: Data from the Osteoarthritis Initiative. BMC Musculoskelet Disord 2016;17: 299. doi: 10. 1186/s 12891-016-1158-9.
Van Rossom S, Wesseling M, Smith CR, et al. The influence of knee joint geometry and alignment on the tibiofemoral load distribution: A computational study. Knee 2019;26: 813-823.
Cooper C, McAlindon T, Coggon D, Egger P, Dieppe P. Occupational activity and osteoarthritis of the knee. Ann Rheum Dis 1994; 53: 90-93.
Manninen P, Heliovaara H, Riihimaki H. Physical workload and the risk of severe knee osteoarthritis. Scand J Environ Health 2002; 28: 25-32.
Zhang Y, Hunter DJ, Nevitt MC, Xu L, et al. Association of squatting with increased prevalence of radiographic tibiofemoral knee osteoarthritis. The Beijing osteoarthritis study. Arthritis Rheum 2004; 50: 1187-1192.
Dahaghin S, Tehrani-Banihashemi SA, Faezi ST, Jamshidi AR, Davatchi F. Squatting, sitting on the floor, or cycling: Are life-long daily activities risk factors for clinical osteoarthritis? Stage III results of a community-based study. Arthritis Care Res 2009; 61: 1337-1342.
Miyazaki T, Uchida K, Sato M, et al. Knee laxity after staircase exercise predicts radiographic disease progression in medial compartment knee osteoarthritis. Arthritis Rheum 2012;64:3908-16.
Barbour KE, Hootman JM, Helmick CG, et al. Meeting physical activity guidelines and the risk of incident knee osteoarthritis: the Johnson county osteoarthritis project. Arthritis Care Res (Hoboken) 2014; 66: 139-146.
Jayabalan P, Kocherginsky M, Chang A, et al. Physical activity and worsening of radiographic finding in persons with or at higher risk of knee osteoarthritis. Arthritis Care Res (Hoboken) 2019; 71: 198-206.
Sharma L, Lou C, Felson DT, et al. Laxity in healthy and osteoarthritic knees. Arthritis Rheum 1999; 42: 861-870.
Lewek MD, Rudolph KS, Snyder-Mackler L. Control of frontal plane knee laxity during gait in patients with medial compartment knee osteoarthritis. Osteoarthritis Cartilage 2004;12: 745-751.
Fitzgerald GK, Piva SR, Irrgang JJ. Reports of joint instability in knee osteoarthritis: Its prevalence and relationship to physical function. Arthritis Rheum (Arthritis Care Res) 2004; 51:941-946.
Van der Esch M, Steultjens M, Knol DJ, Dinant H, Dekker J. joint laxity and relationship between muscle strength and functional ability in patients with osteoarthritis of the knee. Arthritis Rheum (Arthritis Care Res) 2006; 55:953-959.
Schmitt LC, Rudolph KS. Influence on knee movement strategies during walking in persons with medial knee osteoarthritis. Arthritis Rheum 2007; 57: 1018-1026.
Sharma L, Chmiel JS, Almagor O, et al. Knee instability and basic and advanced function decline in knee osteoarthritis. Arthritis Care Res (Hoboken) 2015; 67: 1095-1102.
Chang A, Hayes K, Dunlop D, at al. Thrust during ambulation and the progression of knee osteoarthritis. Arthritis Rheum 2004; 50: 3897-3903.
Sharma L, Chang AH, Jackson RD, at al. Varus thrust and incident and progressive knee osteoarthritis. Arthritis Rheumatol 2017;69:2136-43.
Wink AE, Gross KD, Brown CA, at al. Varus thrust during walking and the risk of incident and worsening medial tibiofemoral MRI lesions: The multicenter osteoarthritis study. Osteoarthritis Cartilage 2017; 25:839-45.
Chang AH, Chmiel JS, Moisio KC, et al. Varus thrust and knee frontal plane dynamic motion in persons with knee osteoarthritis. Osteoarthritis Cartilage 2013; 21: 1668-1673.
Kuroyanagi Y, A quantitative assessment of varus thrust in patients with medial knee osteoarthritis. Knee 2012; 19: 130-4.
Miyazaki T, Uchida K, Wada M, et al.　Anteroposterior and varus-valgus laxity of the knee increase after stair climbing in patients with mild osteoarthritis. Rheumatol Int 2012; 32:2823-8.
Lafortune MA. Three-dimensional acceleration of the tibia during walking and running. J Biomech 1991;24:877-86.
Ogata K, Yasunaga M, Nomiyama H. The effect of wedged insoles on the thrust of osteoarthritic knees. Int Orthop 1997;21:308-12.
Henriksen M, Simonsen EB, Graven-Nielsen T, et al. Impulse-forces during walking are not increased in patients with knee osteoarthritis. Acta Orthop 2006; 77. 650-656.
Kavanagh JJ, Morrison S, James DA, Barrett R. Reliability of segmental accelerations measured using a new wireless gait analysis system. J Biomech 2006; 39: 2863-2872.
Turcot K, Aissaoui R, Boivin K, at al. New accelerometric method to discriminate between asymptomatic subjects and patients with medial knee osteoarthritis during 3-D gait. IEEE Trans Biomed Eng 2008; 55:1415-22.
Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee injury and osteoarthritis outcome score (KOOS) — development of a self-administered outcome measure. J Orthop Sports Phys Ther 1998; 28: 88-96.
Paley D. Normal lower limb alignment and joint orientation. Principles of deformity correction. Berlin Heidelberg: Springer; 2002. pp1-18.
Cohen J. Statistical power analysis for the behavioral sciences. Hilldale: Lawrence Erlbaum Associates; 1988.
Kanda Y. Investigation of the freely available easy-to-use software ’EZR’ for medical statistics. Bone Marrow Transplant 2013; 48:452-458.
Johnson F, Leitl S, Waugh W. The distribution of load across the knee: A comparison of static and dynamic measurements. J Bone Joint Surg Br 1980; 62: 346-349.
Andriacchi TP. Dynamics of knee malalignment. Orthop Clin North Am 1994;25: 395-403.
Maeyama A, Naito M, Moriyama S, Yoshimura I. Evaluation of dynamic instability of the dysplastic hip with use of triaxial accelerometry. J Bone Joint Surg Am 2008; 90: 85-92.
Lee DH, Park SC, Park HJ, Han SB. Effect of soft tissue laxity of the knee joint on limb alignment correction in open-wedge high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc 2016; 24: 3704-3712.
Hess S, Moser LB, Amsler F, Berhrend H, Hirschmann MT. Highly variable coronal tibial and femoral alignment in osteoarthrotic knees: A systematic review. Knee Surg Sports Traumatol Arthrosc 2019; 27: 1368-1377.
Andriacchi TP. Walking speed as a basis for normal and abnormal gait measurements. J Biomech 1977; 10: 261-8.
Luetzner C, Voigt H, Roeder I, Kirschner S, Luetzner J. Placement makes a difference: accuracy of an accelerometer in measuring step number and stair climbing. Gait Posture 2014; 39: 1126-1132.
Luepongsak N, Amin S, Krebs DE, McGibbon CA, Felson D. The contribution of type of daily activity to loading across the hip and knee joints in the elderly. Osteoarthritis Cartilage 2002; 10: 353-359.
Sahlström A, Lanshammar H, Adalberth G. Knee joint moments in work-related situations. Ergometrics 1995; 38: 1352-1359.
Sharma L, Lou C, Cahue S, Dunlop D. The mechanism of the effect of obesity in knee osteoarthritis. The mediating role of malalignment. Arthritis Rheum 2000; 43: 568-575.
Weisman G, Pope MH, Johnson RJ. Cyclic loading in knee ligament injuries. Am J Sports Med 1980; 8: 24-30.
Skinner HB, Wyatt MP, Stone ML, Hodgdon JA, Barrack RL. Exercise-related knee joint laxity. Am J Sports Med 1986; 14: 30-34.
Johannsen HV, Lind T, Jakobsen BW, Kroner K. Exercise-induced knee joint laxity in distant runners. Br J Sports Med 1989; 23: 165-168.
Lewek MD, Ramsey DK, Snyder-Macker L, Rudolph KS. Knee stabilization in patients with medial compartment knee osteoarthritis. Arthritis Rheum 2005; 52: 2845-2853.
Segal NA, Glass NA, Torner J. et al. Quadriceps weakness predicts risk for joint space narrowing in women in the MOST cohort. Osteoarthritis Cartilage 2010; 18: 769-775.
Øistad BE, Juhl CB, Eitzen I, Thorlund JB. Knee extensor muscle weakness in a risk factor for development of knee osteoarthritis. a systemic review and meta-analysis. Osteoarthritis Cartilage 2015;23: 171-177.
Elboim-Gabyzon M, Rozen N, Laufer Y. Quadriceps femoris muscle fatigue in patients with knee osteoarthritis. Clin Interv Aging 2013; 8: 1071-1077.

Correlation of Knee Instability With Alignment And Repetitive Physical Activity In Patients With Knee Osteoarthritis: A Cross-Sectional Study

Status:

Version 1

Abstract

Figures

Introduction

Methods

Subjects

Clinical evaluation

Assessment of muscle strength

Radiography

Accelerometry

Statistical analysis

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Supplementary Files

Status:

Version 1