The effects of impaired joint position sense on the development and progression of pain and structural damage in knee osteoarthritis

Abstract

Objectives

While cross sectional studies have reported impaired proprioceptive acuity in persons with OA, there have been no longitudinal studies to evaluate whether those with such impairments increase the risk of OA or its worsening.

Methods

We studied subjects from the MOST study, a longitudinal study of persons with or at high risk of knee OA. At baseline, we quantified acuity as the amount of a subject's error when attempting to reproduce a test knee flexion angle (a measure of joint position sense). We tested proprioception 10 times in the right leg and used a person's worst score as their proprioceptive acuity. At baseline and 30 month follow-up, we assessed the presence of frequent pain, obtained WOMAC scores and acquired PA and lateral weight bearing knee x-rays read for Kellgren and Lawrence grade and individual radiographic features. We examined the relation of baseline proprioceptive acuity In quartiles with baseline knee pain (frequent pain (yes/no) and WOMAC pain score, self reported physical function and x-ray OA and with changes from baseline in pain, physical function and x-ray OA adjusting analysis for age, sex body mass index and quadriceps strength.

Results

At baseline, proprioceptive acuity was associated with the presence and severity of knee pain but not with the presence of radiographic OA. However, among the 2243 subjects with baseline acuity assessments and 30 month follow-up, there were no strong associations between proprioceptive acuity and development of adverse osteoarthritis outcomes. Acuity was not significantly associated with the new onset of frequent knee pain. Those in the quartile with worst acuity at baseline had slightly greater worsening of WOMAC pain (0.47 on a 20 point scale) and physical function scores (by 1.5 points on a 0-68 scale) compared with those with best proprioceptive acuity whose pain and physical function score deteriorated but less (For pain p = .05; for physical function p = 0.02). X-ray worsening was not significantly associated with proprioceptive acuity.

Conclusions

Proprioceptive acuity as assessed by the accuracy of reproduction of the angle of knee flexion has modest effects on the trajectory of pain and physical functional limitation in knee OA.

Proprioception is the conscious perception of body position, loading and movement (1). The physiological systems that contribute to proprioceptive acuity include visual and vestibular systems, articular, cutaneous and muscle mechanoreceptors. Input from these systems are integrated with other information and used to plan and effect finely controlled muscle contraction enabling smooth, coordinated movement.

There is some evidence that impaired proprioceptive acuity may be involved in the pathogenesis of osteoarthritis (OA). In animals subjected to joint trauma, impaired sensory input increases the risk of developing OA (2). In humans, proprioceptive deficits are greater in people with knee OA compared with people of a similar age without disease (1;3-7) These deficits are also seen in the contralateral legs of people with unilateral OA who have a high risk of developing bilateral OA(8), and in people with Charcot arthropathy, severe impairment of position sense accelerates joint degeneration after minor joint injury. Proprioception deficits may result in poorly controlled, excess loading to the knee during gait initiating or accelerating joint degeneration(6) (9) (10).

Unfortunately, the cross-sectional design of all of these studies limit our ability to investigate whether impaired proprioceptive acuity which we shall examine as joint position sense precedes the occurrence of OA or accelerates disease progression. In addition, all previous studies have compared people with clinical OA to age-matched healthy controls. Because clinical OA encompasses structural damage and symptoms (pain and physical functioning) these studies cannot discriminate the association between impaired proprioception with pain, disability or structural damage.

Elucidating the role of proprioceptive deficits in the etiology and progression of OA may be important because proprioceptive acuity may be modifiable factor (7), and interventions that improve proprioceptive acuity might prevent or ameliorate some of the effects of OA.

To investigate the role of proprioceptive deficit in the development and progression of knee OA, we undertook a prospective, longitudinal assessment of proprioceptive acuity and its relation to the trajectory of knee OA, examining radiographic change, symptoms and disability in a large cohort of people.

Methods

Study Design and Subjects

The Multicenter Osteoarthritis Study (MOST) is a large, prospective, epidemiological study of people with OA or at high risk of developing OA (11). The goal of the MOST study is to identify risk factors for incident and progressive knee OA in a sample of older adults who either have the disease or are at high risk of developing it. Those considered at high risk included persons who were overweight or obese, had knee pain on most of the last 30 days, had a history of knee injury that made it difficult to walk for at least one week, or reported previous knee surgery. High risk due to overweight was defined as present when a person weighed more than the median weight of persons of the same age and gender from the Framingham OA Study. (12;13) For example, the weight cut-off for women for 50-59-years old was 70 kg; for women 60-69 years, 68 kg; and for women 70-79 years, 67 kg. Weight cutoffs for men also varied by age as follows:: 50-59-years, 88 kg; 60-69 years, 84 kg; and 70-79 years, 83 kg.

Subjects aged 50 to 79 years were recruited from two U.S. communities, Birmingham, Alabama and Iowa City, Iowa through mass mailing of letters and study brochures supplemented by media and community outreach campaigns. Each center also recruited ethnic minorities reflecting their local population. Subjects were excluded if they had rheumatoid arthritis(14), ankylosing spondylitis, psoriatic arthritis, chronic reactive arthritis, kidney disease necessitating hemo- or peritoneal dialysis, a history of cancer (except for nonmelanoma skin cancer), bilateral knee replacement surgery, inability to walk without the help of another person or walker, or if they were planning to move out of the area in the next three years.

The study protocol was approved by IRB's at the University of Iowa, University of Alabama, Birmingham, University of California, San Francisco and Boston University Medical Campus.

Proprioceptive acuity

Proprioceptive acuity relies on joint position sense, which we assessed using a protocol developed by Hurley(15). The protocol instructs a subject to attempt to reproduce a randomly chosen angle of knee flexion. Each subject is blindfolded and instructed to sit quietly with their legs dangling off the end of a raised chair. A table just above the thighs further obstructs any view of their legs. We attached an electrogoniometer to the outside of the right leg. A SG150 twin axis electrogoniometer (Penny and Giles) was attached to the lateral aspect of their right lower leg using adhesive tape, the upper block just below and in line with the head of the fibula and the lower block just below and in line with the lateral malleolus. The goniometer was connected by C1000 leads to a handheld ADU301 display unit that gave a continuous real-time digital reading of knee flexion angle.

From this “start position” with legs dangling, the subject was asked to very slowly extend their leg to a predetermined position, which they held for 5 seconds. They were then asked to relax and let their leg slowly return to the start position. After 3 seconds they were then asked to reproduce the test position, and the knee angle displayed on the display unit at this “reproduced position” was recorded. As the movement was voluntary no pre-defined speed could be imposed, but as an approximate idea of the speed of movement it would take subjects about 10 seconds to move their lower leg through an arc of about 90° We repeated this process 10 times each time at a slightly different predefined flexion angle so as to test a wide range of knee flexion, obtaining 10 measures of proprioceptive acuity from each subject using the right leg. For each trial, proprioceptive acuity was taken as the difference between the knee angles recorded from the display unit at the “test position” and “reproduced position”.

Since our primary interest was in determining whether or not knee joints might be injured by poor proprioceptive acuity and thereby cause pain and structural damage, we chose to focus mainly on a subject's worst measured proprioceptive acuity of the 10 trials. We chose to look at this in preference to the average inaccuracy in joint position sense across all trials since a subject's worst acuity is more likely to provide an accurate characterization of their exposure to sub-clinical injuries. Variability in proprioception test results(16) was expected since this reflects a wide variation in human performance. Indeed, in predicting walking speed, one group of investigators has shown the the variability around the mean joint position sense predicted walking speed whereas the mean joint position sense did not.(17). We also examined the mean inaccuracy across all trials as a secondary measure of proprioceptive acuity.

Pain

At baseline and 30 month clinic visit follow-up assessment all subjects were asked the following question about frequent knee pain, “During the past 30 days, have you had pain, aching, or stiffness in your knee on most days?”. We characterized a knee with no pain at baseline but with pain at 30 months as new knee pain.

At the baseline and 30 month assessment, subjects completed the WOMAC questionnaire and filled out surveys on medication use and were weighed and measured. BMI was computed as weight/height².

Structural damage on X-ray

At baseline and at the 30 month follow-up, all subjects underwent weight-bearing posteroanterior fixed flexion knee radiographs using the protocol of Peterfy(18). Body weight was equally distributed between the two legs, and the great toes of feet and the front of thighs were placed in contact with the front plate of a plexiglass frame. The external rotation of feet was fixed at 10 degrees using a V-shaped foot angulation support on the frame. The central x-ray beam was directed to the midpoint between back of the knees at ∼10 degrees caudal angle to allow the anterior and posterior lips of the medial tibial plateau to be optimally superimposed (film-focus distance 183 cm). Lateral weight bearing films of each knee were also obtained at baseline and 30 months using the Framingham OA Study protocol(19).

An experienced musculoskeletal radiologist and a rheumatologist, both blinded to clinical data, graded all PA films according to the scheme of Kellgren and Lawrence (K/L) and scored individual radiographic features including joint space narrowing (JSN) 0-3 using the OARSI atlas(20). Lateral films were read using the protocol described in LaValley et al(19) in which joint space width is also scored 0-3 in medial and lateral tibiofemoral and patellofemoral compartments. Atlases and protocols for AP and lateral view readings are targeted toward cross sectional evaluations of joint space width. In preliminary readings, we found that knees often showed joint space narrowing longitudinally but did not show enough narrowing to move from one grade to the next (e.g. 1 to 2). When joint space narrowed but when narrowing did not reach a full grade on the 0-3 scale, readers were instructed to use ½ grades. (21).

For knees with x-ray OA (K/L >=2 or patellofemoral OA by x-ray), we defined x-ray progression as any increase in K/L score or joint space width score in either the tibiofemoral or patellofemoral compartment. For knees without x-ray OA, we defined incident OA as new onset K/L >=2 grade or patellofemoral OA(22). We counted knees that had a knee replacement at follow-up and that did not have K/L grade 4 or bone on bone narrowing at baseline as having experienced progression.

X-rays were read paired. Readers were blinded to the proprioceptive status of the participant. Each person's knee films were read by both readers working independently. If readers disagreed on the presence of progression (for knees with OA at baseline) or incidence (for knees without x-ray OA at baseline), the film readings were adjudicated by a panel of 3 readers (PA, BS and DTF) to decide whether incidence or progression had occurred.

Analyses

As noted above, a subject's worst absolute error between the “test” and “reproduced positions” of the 10 trials of the right knee was used as their measure of proprioception. For example, if of the 10 attempts, a subject's largest error in reproducing the referent flexion angle was 8 degrees, their proprioceptive acuity was considered to be 8 degrees. Based on a person's proprioception score, each subject was placed into a quartile.

Cross sectional and longitudinal analyses focused on the relation of proprioceptive acuity to frequent knee pain (yes/no), WOMAC pain score, and WOMAC physical function score. For 80 knees which underwent knee replacement between baseline and follow-up, we assumed WOMAC pain and physical function scores at follow-up based on mean WOMAC scores in U.S. subjects undergoing knee replacements (23) and adjusted these scores based on the effect of age, sex and baseline BMI on WOMAC scores in all MOST subjects at baseline. In effect the difference between the age/sex/BMI category for each subject on the WOMAC pain/physical function was added (or subtracted) from the mean preknee replacement WOMAC score for those undergoing knee replacement. The relation of proprioceptive acuity to radiological damage was tested in relation to baseline x-ray OA (yes/no), incident OA (restricted to knees without OA at baseline) and progressive OA (knees with OA at baseline). All data is concerned with the right knee only. For dichotomous outcomes, logistic regression was used and for continuous ones (e.g. WOMAC), multiple linear regression was used. Covariates included age, gender, BMI, isokinetic quadriceps strength (using the same leg and tested using a Cybex dynamometer) and others as noted. For the quartile analysis, we used the best acuity as the referent group and present odds ratios for disease (with 95% CI's) for each other quartile. In addition, we tested an ordinal variable (quartiles 1-4) and computed a test for trend as the significance associated with that variable.

Results

There were no important differences in age, gender, prevalence of OA or pain nor proprioceptive acuity in subjects seen at baseline and those seen at both baseline and 30-month follow-up (Table 1)

Table 1.

Baseline Characteristics in whole MOST cohort who had measured proprioception and in those with full follow-up of proprioception

	Whole MOST Cohort (n=2440)	MOST Cohort with Follow-up at 30 months (n = 2224)
PERSON-SPECIFIC RISK FACTORS:
Age (Years; mean ± sd)	62.4 (8.1)	62.4 (8.0)
Gender (% women)	58.9	58.6
BMI (mean ± sd)	30.4 (5.7)	30.3 (5.6)
X-ray OA ≥1 knee TF or PF (%)	51.2	51.5
Frequent Knee Pain (%)	40.9	39.9
KNEE-SPECIFIC RISK FACTORS:
Quadriceps Strength (Newtons; mean ± sd)	92.0 (43.9)	92.6 (44.1)
X-ray OA (%)	39.6	38.2
Frequent Knee Pain (%)	28.5	27.9
WOMAC pain (mean ± sd)	3.3 (3.6)	3.2 (3.5)
Mean Propriocepton Score (degrees, median across subjects)	3.9	3.9
Worst proprioception score (degrees; median across subjects)	8.0	8.0

MOST – Multicentre Osteoarthritis Study

SD – standard deviation

% - percentage

BMI – body mass index

OA osteoarthritis

TF – Tibiofemoral joint

PF – patellofemoral joint

WOMAC – Western Ontario and McMasters OA Index.

At baseline, proprioceptive acuity was associated with both pain and functional limitations (Table 2). WOMAC pain and physical functioning scores were higher (i.e. worse) in subjects who had worse proprioceptive acuity. Prevalence of knee pain at baseline increased from 25.3% among those with the best proprioceptive acuity to 31.5% among those in the worst acuity group (p=0.03 for trend). Prevalence of radiographic knee OA was not related to proprioceptive acuity. (Table 2).

Table 2.

Baseline proprioceptive acuity, pain and physical functioning.

	WOMAC scores *		Knee pain (yes/no)*		Radiological damage
Proprioceptive acuity	WOMAC pain**	WOMAC functioning**	No. (%) with knee pain	Adj. OR of knee pain (95%CI) †	Proportion with X-ray OA (%)	Adj. OR X-ray OA (95%CI) †
Quartile 1 (worst)	3.8	15.1	156/495 (31.5)	1.33 (0.99, 1.78)	191/495 (38.6)	0.87 (0.67, 1.12)
Quartile 2	3.4	14.5	216/717 (30.1)	1.32 (1.01, 1.73)	271/717 (37.8)	0.79 (0.63, 1.00)
Quartile 3	3.2	14.0	167/607 (27.5)	1.18 (0.89, 1.56)	237/607 (39.0)	0.79 (0.62, 1.01)
Quartile 4 (best)	3.0	13.6	157/621 (25.3)	1 (referent)	267/621 (43.0)	1 (referent)
P for trend	<.001	.03		0.03		0.22

^*Knee specific and relate to the limb tested for proprioception

^**WOMAC - Western Ontario and McMasters OA Index scores for all subjects for knee tested only, are least squares means adjusted for age, sex, BMI and isokinetic quadriceps strength

^†Adj OR – adjusted odds ratio were adjusted for age, sex, body mass index and isokinetic quadriceps strength

% - percentage

95%CI - 95 percent confidence interval

Longitudinally, proprioceptive acuity was related modestly to changes in pain and function. (Table 3). Change in WOMAC pain over 30 months was modestly and significantly related to proprioceptive acuity at baseline (p for trend = .05), although the difference in worsening of WOMAC pain scores in persons with the worst acuity at baseline was modest (WOMAC pain scores increased by 0.47 (20 point scale) in those with the worst acuity whereas they increased by only 0.15 for those with the best acuity. Poor proprioceptive acuity was associated with worse physical function at follow up. The change in physical function score worsened by 1.50 points in subjects in the worst proprioceptive acuity group at baseline compared with those with best proprioceptive acuity at baseline whose physical functioning worsened by 0.16 points (P for trend = 0.03). Among subjects with no knee pain at baseline, there was no significant relation between baseline proprioceptive acuity and risk of development of new knee pain, subjects in the worst proprioceptive acuity quartilte were only slightly more likely (14,9%) to develop new knee pain than subjects with best proprioceptive acuity (12.0%).

Table 3.

Proprioceptive acuity at baseline and development of new pain and change in WOMAC pain and physical functioning at 30-month follow-up assessment.

	WOMAC scores *		Knee pain *
Proprioceptive acuity	Change in WOMAC pain at follow up**	Change in WOMAC functioning at follow up**	No. (%) with new knee pain	Adjusted odds ratio of new knee pain (95%CI) †
Worst - Quartile 1	0.47 (worse)	1.50 (worse)	33/222 (14.9)	1.33 (0.78, 2.26)
Quartile 2	0.38	1.08	51/358 (14.3)	1.22 (0.76, 1.95)
Quartile 3	0.19	0.67	43/296 (14.5)	1.24 (0.75, 2.04)
Best - Quartile 4	0.15	0.16	38/317 (12.0)	1 (referent)
P for trend	P= 0.05	P=0.02		P=0.31

^*These are knee specific and relate to the limb tested for proprioception

^**WOMAC - Western Ontario and McMasters OA Index scores for all subjects for knee tested only. These are least squares means adjusted for age, sex, body mass index and isokinetic quadriceps strength

^†Adjusted OR are adjusted for age, sex, body mass index and isokinetic quadriceps strength

% - percentage

95%CI - 95 percent confidence interval

P – Probability

There was no association of proprioceptive acuity at baseline with worsening x-ray OA over time (Table 4). For subjects without knee OA at baseline, those in the worst proprioception grouping had a 1.12 fold increase in the odds of developing OA at 30 months (95%CI 0.62, 2.02). For subjects with knee OA at baseline, the odds for progression was not increased.

Table 4.

Proprioceptive acuity with incident or progressive X-ray OA

	Knees without OA at baseline		Knees with OA at baseline
Proprioceptive acuity	Proportion with incident x-ray OA (%)	Adjusted odds ratio (95%CI)	Proportion with X-ray progression (%)	Adjusted odds ratio (95%CI)
Worst - Quartile 1	21/225 (9.3)	1.17 (0.64, 2.14)	122/213 (57.3)	0.99 (0.68, 1.43)
Quartile 2	25/386 (6.5)	0.58 (0.32, 1.05)	114/214 (53.3)	0.93 (0.65, 1.33)
Quartile 3	20/320 (6.3)	0.70 (0.38, 1.28)	128/219 (58.5)	1.05 (0.73, 1.51)
Best - Quartile 4	31/347 (8.9)	1 (referent)	203/358 (56.7)	1 (referent)

OA – Osteoarthritis

% - percentage

95%CI - 95 percent confidence interval

We focused on the worst acuity displayed by a person during their testing, as we felt this was more valid than using the mean score. We carried out additional analyses using the mean score and findings were similar. The mean inaccuracy in joint position sense was significantly related to WOMAC pain and physical function scores at baseline after adjustment for age, sex, bmi and quadriceps strength. This mean inaccuracy was also modestly related to later change in WOMAC pain (p for trend = .055 with worse category experiencing an increase in WOMAC pain of 0.63 vs. an increase of 0.16 among those in the best category). For WOMAC physical function, mean inaccuracy was associated with worse later function (p for trend =.07); those in the worst category had an increase of 1.96 in score vs. an increase by only 0.40 in those in the best group. The differences between the worst and best acuity groups (unlike the test for trend) showed significant differences for both WOMAC pain and physical function scores. Like our measure of worst acuity, mean acuity was not related to x-ray OA.

Discussion

This is the first longitudinal study of proprioceptive acuity as a risk factor for the initiation and progression of pain and structural damage in knee OA. Our baseline findings confirm previous cross-sectional studies reporting a relationship between poor proprioceptive acuity and worse pain and physical functioning. Although our longitudinal findings showed that people with greater proprioceptive deficits were at increased risk of deteriorating physical function and more severe pain, these effects were modest and their clinical relevance unclear. We did not find that proprioceptive deficits affect the risk of new OA or new knee pain. Our data therefore suggests that proprioceptive deficits at least as assessed by a person's ability to reproduce a knee flexion angle are not a major risk factor for OA.

The major strengths of this study are its size and longitudinal design. Our failure to find that proprioceptive acuity had a major effect on knee OA outcomes is unlikely to be a consequence of inadequate power, since this study is a large study, the largest yet undertaken and confidence intervals were narrow especially for baseline analyses and even for x-ray progression. When we looked at the average inaccuracy in joint position sense across all 10 trials in individuals, we found similar inaccuracy (3.9°) as reported in other studies ((24); (25) This strengthens confidence in the generalizability of our inferences.

However, several limitations of the study may mask any effect of proprioceptive deficit. The most important limitations are the difficulty in measuring proprioception and the insensitivity of the tools used to measure the outcomes. Accurate proprioception is essential for planning, executing and monitoring safe, efficient movement. To ensure that the body has an accurate “real time” picture of what is happening, it collects collates and assimilates sensory information from several overlapping physiological systems. If one physiological system is compromised, others compensate to minimize sensory deficits. This makes measuring proprioception problematic(15;16;26) and could prevent us detecting associations between proprioceptive deficits.

There are several ways of measuring proprioceptive acuity. One often used is the threshold detection of passive movement, but passive movements do not reflect real life movement or function. We estimated people's ability to replicate limb position using active movement as this maximizes sensory input to the central processing systems and replicates normal movement which is almost always active, and as such is a closer measure of “real life” proprioceptive acuity. The technique does require concentration and cognitive skills by the subjects if these skills are compromised, this will interfere with the accurate estimation of proprioception. Other investigators have suggested there is a poor correlation between different approaches to proprioception assessment (27).

Similarly, X-rays are an insensitive measure of structural joint damage, so that the poor correlation between proprioception and joint damage might be partially due to insensitive outcome measures. Since x-ray damage is weakly related to function loss and pain in OA, one might argue that any factor related to pain and function in OA might not be expected to correlate with x-ray OA. In addition, since OA is a slowly progressive condition despite this study involving a relatively long follow-up it may still be too short to see changes in structural damage and proprioception.

Many factors may combine to worsen a patient's course, and proprioceptive deficits may be only one of them, one which may not have a unique independent effect. People may accommodate for (sub)conscious proprioceptive decline by adapting their behavior. Thus. impaired proprioception may explain why people with symptomatic OA walk more slowly and with longer doublTe limb stance to avoid risk of joint injury and prevent worsening disease (4) (28) These compensatory mechanisms could also explain the lack of association between poor proprioception and progression of OA. The modest association of joint position sense and function loss and pain worsening may not relate to OA progression at all but rather to poor motor control and muscle function in those with impaired proprioception and the contribution of these with pain and function.

Subjective assessment of pain and physical function, as measured by the WOMAC, is influenced by many psychological factors, traits and emotions. Therefore, a weak relationship between structural articular damage, pain and impaired proprioception is not be surprising, and reflects the well described lack of association between structural damage, pain and disability. Including an objective measure of physical function might have provided a better comparison to assess the effect of proprioception on physical function.

The severity of the condition may affect the association between proprioception and outcomes measures (3;7). From the baseline pain (mean WOMAC score about 3 from a possible range of 0-best to 20-worst), physical functioning (WOMAC score of approximately 14 from a possible range of 0-best to 64-worst) and percentage of people with radiological damage suggest the cohort recruited into the MOST study from the community had mild disease. In early stages of disease when overlapping protective strategies function well, proprioception deficits may not emerge as identifiable risk factors for disease. Perhaps it is only when disease is farther advanced and all protective strategies are impaired that proprioception deficits play a critical role.

In summary, poor proprioceptive acuity as assessed by joint position sense is related cross-sectionally with the presence of knee pain and its severity and worse physical functional limitations. However, it is not strongly related to risk of later outcomes---we found no significant relations with new knee pain or x-ray worsening. We did find that, compared to those with good proprioceptive acuity, persons with poor acuity had more deterioration in physical function and worse pain over time but the associations were modest.