To determine the prevalence of pre–radiographic osteoarthritis (ROA) and ROA of the knee in a symptomatic population-based cohort, and to evaluate the clinical correlates of pre-ROA and ROA.
To determine the prevalence of pre–radiographic osteoarthritis (ROA) and ROA of the knee in a symptomatic population-based cohort, and to evaluate the clinical correlates of pre-ROA and ROA.
Subjects ages 40–79 years with knee pain were recruited as a random population sample and classified using magnetic resonance cartilage (MRC) scores (range 0–4) and Kellgren/Lawrence (K/L) scale grades (range 0–4) as no OA (MRC score <2, K/L grade <2), pre-ROA (MRC score ≥2, K/L grade <2), and ROA (MRC score ≥2, K/L grade ≥2). Logistic regression was used to evaluate the association of clinical variables with cartilage defects, comparing subjects with any cartilage defects (pre-ROA/ROA) with those without, and to determine associations with individual OA subgroups.
Of 255 symptomatic subjects, no OA, pre-ROA, and ROA were seen in 13%, 49%, and 38%, respectively. The prevalence of pre-ROA/ROA compared with no OA was associated with age (odds ratio [OR] 2.89, 95% confidence interval [95% CI] 1.59–5.26), sports activity (OR 1.35, 95% CI 1.07–1.70), abnormal gait (OR 10.86, 95% CI 1.46–1,388.4), effusion (OR 16.58, 95% CI 2.22–2,120.5), and flexion contracture (OR 2.37, 95% CI 1.50–3.73). The prevalence of ROA versus no OA was significantly associated with age, body mass index, pain frequency, pain duration, severe knee injury, sports activity, gait, effusion, bony swelling, crepitus, flexion contracture, and flexion. The prevalence of pre-ROA versus no OA was increased with age, sports activity, effusion, and flexion contracture, and reduced with valgus malalignment.
Cartilage defects were highly prevalent in this symptomatic population-based cohort, with 49% of subjects having pre-ROA and 38% having ROA. Prevalent cartilage defects were significantly associated with age, sports activity, abnormal gait, effusion, and flexion contracture.
Arthritis is highly prevalent, with physician-diagnosed arthritis occurring in more than 30% of persons ages 45–64 years and in more than 50% of persons ages >65 years, and is the leading cause of disability (1). The prevalence of radiographic knee osteoarthritis (OA) was reported to be 9.5% in symptomatic patients ages ≥63 years (2) using the standard radiologic definition of a Kellgren/Lawrence (K/L) scale grade ≥2 (3). However, the prevalence of OA is highly dependent on its definition. In a review of community burden, persistent knee pain was estimated to occur in 25% of the population age >55 years (4). The discrepancy between clinically and radiographically defined OA has been reported previously in a study using First National Health and Nutrition Examination Survey data (5). Of those with knee pain, only 15% had evidence of radiographic OA (ROA), yet 59% had received a diagnosis of arthritis by a physician (5). This discrepancy may be due to the presence of clinical abnormalities in the absence of radiographic ones. Although there is currently no accepted definition of OA using magnetic resonance imaging (MRI), cartilage degenerative changes can be seen on MRI prior to radiographic abnormalities. In an MRI study of women ages 35–55 years, of those with knee pain but with normal radiographs, 55% had cartilage defects on MRI, suggesting that the prevalence of OA may be underestimated by radiography in symptomatic subjects (6).
If the prevention of knee OA is to succeed, early recognition and diagnosis may be critical. Therefore, in people with knee pain, the identification of specific signs or symptoms that are associated with OA, especially early-stage disease, would be clinically valuable because it would allow for the targeting of earlier intervention. Previous studies have reported variable success with finding specific clinical features associated with radiographic knee OA (7–9) or with MRI findings in those with radiographic disease (10). The association of clinical findings with MRI-identified pre-ROA has not been reported.
In this symptomatic population-based cohort study, we were interested in determining the prevalence of pre-ROA based on the presence of cartilage defects on MRI in the absence of osteoarthritic changes on radiograph, as well as the prevalence of ROA, and we evaluated the clinical correlates of pre-ROA and ROA. Specifically, our objective was to evaluate the association of clinical variables with prevalent cartilage defects, i.e., in subjects with pre-ROA or ROA (pre-ROA/ROA) compared with those with no cartilage defects or no OA, and to determine which variables were associated with subgroups of pre-ROA and ROA compared with no OA and compared with each other.
Subjects with knee pain were recruited as a random population sample in the Greater Vancouver area in Canada. Recruitment used a multistage screening process. A random list of households was obtained from the telephone directory listings, which included address and telephone information. Invitation letters were mailed to randomly selected households. This was followed by standardized telephone screening for preliminary eligibility, followed by in-person detailed eligibility screening. A summary of recruitment is shown in Figure 1. A total of 8,523 phone numbers were contacted. Of these, 2,337 (27.4%) were fax or business numbers, numbers not in service, or no contact was made, and 955 (11.2%) were non–English-speaking households. The high rate of non–English-speaking households is consistent with the large proportion of the Asian population of approximately 40% in the Greater Vancouver area. Of 5,231 English-speaking households, 3,269 (62.5%) agreed to participate in the screening survey. Of the 3,269 participating household members, 91.9% were not eligible, with the majority of exclusions being due to age (42.6%) and knee pain/knee exclusion criteria (26.1%). Less frequent exclusions were due to a full stratum (15.9%), no interest to attend the study center (5.0%), rheumatologic conditions (1.3%), inability to undergo MRI (0.3%), and miscellaneous other reasons (0.7%). Eligible subjects (n = 265) were invited to attend the study center. Of these, 255 were enrolled in the study and completed all of the study requirements. Inclusion required: 1) age 40–79 years, 2) pain, aching, or discomfort in or around the knee on most days of the month at any time in the past, and 3) any pain, aching, or discomfort in or around the knee in the past 12 months. Inclusion criteria 2 and 3 were based on a previous study by O'Reilly et al (11) evaluating the prevalence of knee pain in the population, and were determined to be the most appropriate for recruitment of subjects with earlier stages of OA. Exclusion criteria consisted of: 1) inflammatory arthritis or fibromyalgia, 2) knee arthroplasty, 3) knee injury or surgery within the past 6 months, 4) knee pain referred from the hips or back, and 5) inability to undergo MRI. A history of inflammatory arthritis or fibromyalgia was ascertained as a physician-diagnosed self-report and by clinical examination. Referred pain was assessed based on clinical examination. Knee injury was ascertained in the initial telephone screening and at the time of the study visit. In subjects with bilateral knee pain, the more symptomatic knee was used as the study knee. The target enrollment was 255 subjects. To ensure adequate representation from each age decade by sex stratum (8 subgroups in total), recruitment within each stratum was capped at 34 subjects. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Clinical Research Ethics Board, University of British Columbia. All of the subjects provided written informed consent.
Subjects were evaluated with a comprehensive questionnaire to assess knee symptoms and OA risk factors. Subjects were evaluated for duration of knee pain, frequency of pain (number of days over the past month), and pain location using a knee diagram (12). Knee pain location was classified as medial, lateral, patellar, and popliteal using a grid. Assessment of OA risk factors included self-reported weight and height, currently and at age 25 years. Body mass index (BMI) was calculated (weight [kg]/height squared [m2]). History of severe knee injury (requiring a walking aid for >1 week), mild knee injury (not requiring a walking aid for >1 week), and meniscectomy was ascertained, as well as the duration of regular sports activity (at least once weekly) after age 20 years. A standardized knee examination was performed by a rheumatologist (JC) previously shown to have high interobserver reliability (13). A random selection of 11% of subjects underwent a standardized knee examination by a second rheumatologist (JME). The agreement among the 2 examiners ranged from 62–100%, with the exception of quadriceps atrophy, crepitus, and bony swelling, where agreement was 59%, 54%, and 54%, respectively. Physical examinations included assessments for malalignment by inspection (normal, varus, valgus), gait by inspection (normal, abnormal), quadriceps atrophy (none, mild, severe), quadriceps strength (normal, mild weakness, severe weakness), effusion (absent, present), bony swelling (none, mild, moderate, severe), general passive crepitus (none, fine, coarse), anserine bursa tenderness (absent, present), flexion range of motion (ROM) by goniometer (degrees), and flexion contracture by goniometer (degrees). Quadriceps atrophy, quadriceps strength, bony swelling, and crepitus were dichotomized (normal, abnormal) for this analysis. The presence of hand OA was determined using the American College of Rheumatology criteria (14) and classified as symptomatic or asymptomatic. Subjects completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), version VA3.1, a validated instrument widely used in the assessment of knee OA (15).
Radiograph and MRI assessments were completed within a month of the clinic visit and have been described in detail previously (16). Briefly, knee radiographs were obtained using a fixed flexion technique with the SynaFlexer positioning frame (Synarc) (17) and a skyline view in the supine position. Radiographs were scored blinded to clinical and MRI information by 2 independent readers (JC, SN) using the K/L scale grading (range 0–4) (3) with adjudication of reading differences by consensus.
MRI was performed on a GE 1.5T magnet (GE Healthcare) using a transmitter–receiver extremity knee coil. The imaging protocol included 4 MRI sequences: 1) fat-saturated T1-weighted 3-dimensional spoiled gradient-recalled acquisition in the steady state sequence with images obtained in the sagittal plane with reformat images in the axial and coronal planes (repetition time [TR] 52 msec, time to echo [TE] 10 msec, flip angle 60°, field of view [FOV] 12 cm, matrix 256 × 128, section thickness 1–1.5 mm, with 1 signal averaged); 2) fat-saturated T2-weighted fast spin-echo (FSE) sequence with images obtained in the coronal plane (TR 3,000 msec, TE 54 msec, echo train length [ETL] 8, FOV 14 cm, matrix 256 × 192, section thickness 4 mm, with an intersection gap of 1 mm with 2 signals averaged); 3) T1-weighted FSE sequence with images obtained in the oblique sagittal plane (TR 450 msec, TE minimum full, ETL 2, band width 20 Hz/pixel, FOV 16 cm, matrix 384 × 224, section thickness 4 mm, with an intersection gap of 1 mm with 2 signals averaged); and 4) T2-weighted FSE sequence with images obtained in the oblique sagittal plane (TR 4,025 msec, TE 102 msec, ETL 17, band width 20 Hz/pixel, FOV 16 cm, matrix 320 × 288, section thickness 3 mm, with an intersection gap of 0 mm with 4 signals averaged).
Six joint areas were assessed, including medial and lateral tibial plateaus and femoral condyles, and patella and trochlear groove. Cartilage was graded on a 0–4 semiquantitative scale based on the following definitions, previously described by Disler et al (18): 0 = normal, 1 = abnormal signal without a cartilage contour defect, 2 = contour defect of <50% cartilage thickness, 3 = contour defect of 50–99% cartilage thickness, and 4 = 100% cartilage contour defect with subjacent bone signal abnormality (Figure 2). MRI was read by a single reader (AG) blinded to radiograph and clinical information. Intrarater reliability of cartilage readings was high, ranging from 0.84–1.0 for different cartilage surfaces.
Based on radiograph and MR cartilage (MRC) scores (using the worst cartilage lesion to determine the MRC score), subjects were classified into 3 subgroups, defined as follows: no OA = MRC score <2 and K/L grade <2, pre-ROA = MRC score ≥2 and K/L grade <2, and ROA = MRC score ≥2 and K/L grade ≥2. MRI has high sensitivity and specificity for the detection of cartilaginous defects (18–20). Isolated patellofemoral disease on radiograph was uncommon, affecting only 4 (1.6%) of 255 subjects. The inclusion of skyline view data from isolated patellofemoral disease did not change the findings from this study.
It should be noted that some variables, such as joint effusion or anserine bursitis, were also assessed on MRI. However, we elected to test only clinically assessed variables for their association with stage of disease, since these can be performed quickly and inexpensively in a clinical setting and therefore may prove useful in future developments of clinical diagnostic tools.
Data were summarized by OA subgroups using frequencies, means ± SDs, or medians (interquartile ranges), as appropriate. To determine the association of clinical variables with specific sets of OA states, logistic regression was used, adjusted for age, sex, and BMI, to determine the odds ratios (ORs) and 95% confidence intervals (95% CIs) of the variable's association with OA status for each of the following comparisons: 1) pre-ROA/ROA versus no OA, 2) ROA versus no OA, 3) pre-ROA versus no OA, and 4) ROA versus pre-ROA. For analyses that involved a zero cell count, ORs were obtained using Firth's penalized maximum likelihood method (21). All analyses incorporated stratum sampling weights and were performed using SAS, version 9.1.3 (SAS Institute).
Two hundred fifty-five subjects with knee pain were enrolled in the study. Of these, 33 (13%) had no OA, 124 (49%) had pre-ROA, and 98 (38%) had ROA. Demographic and clinical descriptive results for the no OA, pre-ROA, and ROA groups are shown in Table 1. Subjects with ROA were older and had higher BMI currently and at age 25 years, pain duration, pain frequency, and total WOMAC scores. Self-reported pain occurred most commonly in the medial and patellar locations in all 3 groups. A history of severe knee injury and a history of meniscectomy was significantly more common in the ROA group (P = 0.011 and P < 0.0001, respectively). Symptomatic and asymptomatic hand OA was more common in ROA and pre-ROA, but this was not statistically significant.
|No OA (n = 33)||Pre-ROA (n = 124)||ROA (n = 98)||P†|
|Median age, years||47||54||65||< 0.0001|
|Median current BMI, kg/m2||24.1||25.1||26.6||0.0045|
|Median BMI at age 25 years, kg/m2||22.0||21.6||22.8||0.026|
|Median pain duration, years||4.6||5.1||11.4||0.0016|
|Median knee pain frequency, days/month||20.0||18.5||30.0||0.0041|
|Median total WOMAC normalized (range 0–100)||10.2||7.9||19.7||0.0006|
|History of severe knee injury||9.1||10.5||23.5||0.011|
|History of mild knee injury||27.3||31.5||29.6||0.81|
|History of meniscectomy||0||0.8||10.2||< 0.0001|
|Median regular sports activity after age 20 years, years||10||20||10||0.04|
|Symptomatic hand OA||15||22||30||0.15|
|Asymptomatic hand OA||24||30||33||0.89|
|Any hand OA||39||52||69||0.14|
|Varus malalignment||0||1||11||< 0.0001|
|Any malalignment||15||6||37||< 0.0001|
|Abnormal gait||0||5||27||< 0.0001|
|Bony swelling||27||27||63||< 0.0001|
|Any crepitus||61||61||92||< 0.0001|
|Medial tibiofemoral tenderness||52||48||63||0.068|
|Lateral tibiofemoral tenderness||36||25||33||0.40|
|Patellar tendon tenderness||18||11||10||0.22|
|Anserine bursa tenderness||39||26||42||0.021|
|Patellofemoral grind test||24||16||26||0.16|
|Median flexion, degrees||136||136||130||< 0.0001|
|Median flexion contracture, degrees||0||1||3||< 0.0001|
On knee examination, valgus malalignment was most common in ROA (P = 0.002), whereas varus malalignment was seen almost exclusively in ROA (11% ROA, 1% pre-ROA, and 0% no OA; P < 0.0001) (Table 1). Other variables that were statistically significantly different in the 3 OA groups (Table 1) included abnormal gait (P < 0.0001), quadriceps atrophy (P = 0.0058), quadriceps weakness (P = 0.0014), effusion (P < 0.0001), bony swelling (P < 0.0001), and coarse crepitus (P = 0.0002). Anserine bursa tenderness was least prevalent in the pre-ROA group (39% no OA, 26% pre-ROA, and 42% ROA; P = 0.021). Flexion ROM was reduced and degree of flexion contracture increased significantly in ROA (P < 0.0001 for both).
The prevalence of cartilage defects (pre-ROA/ROA) compared with no cartilage defects (no OA) increased with age (OR 2.89, 95% CI 1.59–5.26 for each 10-year increase), regular sports activity after age 20 years (OR 1.35, 95% CI 1.07–1.70 for each 10-year increase), abnormal gait (OR 10.86, 95% CI 1.46–1,388.40), presence of effusion (OR 16.58, 95% CI 2.22–2,120.51), and flexion contracture (OR 2.37, 95% CI 1.50–3.73 for each 3.7° increase).
The prevalence of ROA compared with no OA significantly increased with age (OR 4.77, 95% CI 2.43–9.36), BMI (OR 1.69, 95% CI 1.06–2.71), higher knee pain frequency (OR 1.75, 95% CI 1.16–2.65) and knee pain duration (OR 1.60, 95% CI 1.14–2.25), regular sports activity after age 20 years (OR 1.32, 95% CI 1.02–1.72), history of severe knee injury (OR 5.08, 95% CI 1.34–19.2), abnormal gait (OR 23.26, 95% CI 3.06–2,984.41), effusion (OR 37.46, 95% CI 5.01–4,793.05), bony swelling (OR 4.12, 95% CI 1.66–10.2), crepitus (OR 8.09, 95% CI 2.89–22.7), and flexion contracture (OR 4.96, 95% CI 2.67–9.21), and ROA prevalence decreased with greater degree of knee flexion (OR 0.30, 95% CI 0.15–0.61).
The prevalence of pre-ROA compared with no OA significantly decreased with valgus malalignment (OR 0.23, 95% 0.06–0.83) and increased with age (OR 2.24, 95% CI 1.18–4.25), regular sports activity after age 20 years (OR 1.36, 95% CI 1.07–1.73), effusion (OR 13.14, 95% CI 1.72–1,687.79), and flexion contracture (OR 1.73, 95% CI 1.05–2.85).
The prevalence of ROA compared with pre-ROA was statistically significantly associated with all variables except regular physical activity (Table 2). The strongest associations were seen for history of meniscectomy, malalignment, abnormal gait, and crepitus, although these point estimates were not precise, as can be seen from the large confidence intervals.
|Unit for the OR||Pre-ROA/ROA vs. no OA, OR (95% CI)||ROA vs. no OA, OR (95% CI)||Pre-ROA vs. no OA, OR (95% CI)||ROA vs. pre-ROA, OR (95% CI)|
|Age, years||Per 10 years||2.89 (1.59–5.26)†||4.77 (2.43–9.36)†||2.24 (1.18–4.25)†||2.13 (1.62–2.79)†|
|BMI, kg/m2||Per 5 units||1.33 (0.86–2.05)||1.69 (1.06–2.71)†||1.10 (0.68–1.77)||1.54 (1.16–2.05)†|
|Severe knee injury||Yes vs. no||2.99 (0.84–10.7)||5.08 (1.34–19.2)†||1.81 (0.47–7.03)||2.80 (1.24–6.31)†|
|History of meniscectomy||Yes vs. no||3.64 (0.46–472)‡||7.95 (0.97–1,032)‡||0.81 (0.04–120)‡||9.77 (2.23–91.68)†|
|Regular sports activity after age 20 years||Per 10 years||1.35 (1.07–1.70)†||1.32 (1.02–1.72)†||1.36 (1.07–1.73)†||0.97 (0.81–1.17)|
|Knee pain duration, years||Per 10 years||1.33 (0.96–1.84)||1.60 (1.14–2.25)†||1.14 (0.79–1.64)||1.40 (1.12–1.76)†|
|Knee pain frequency, days||Per 10 days||1.33 (0.92–1.92)||1.75 (1.16–2.65)†||1.13 (0.77–1.66)||1.55 (1.16–2.07)†|
|WOMAC total (range 0–100)||Per 10 points||1.06 (0.82–1.36)||1.30 (0.99–1.71)||0.87 (0.64–1.17)||1.50 (1.21–1.85)†|
|Alignment||Varus vs. nonvarus||2.93 (0.36–382)‡||7.18 (0.84–940)‡||0.73 (0.04–107)‡||9.86 (2.15–94.1)†|
|Alignment||Valgus vs. nonvalgus||0.75 (0.26–2.20)||1.77 (0.58–5.41)||0.23 (0.06–0.83)†||7.79 (2.96–20.5)†|
|Alignment||Any malalignment vs. normal||0.95 (0.33–2.74)||2.27 (0.76–6.80)||0.27 (0.08–0.94)†||8.53 (3.49–20.8)†|
|Abnormal gait||Yes vs. no||10.86 (1.46–1,388)§||23.26 (3.06–2,984)§||3.49 (0.39–460.3)‡||6.66 (2.84–17.92)†|
|Quadriceps weakness||Yes vs. no||2.31 (0.53–10.2)||4.53 (1.00–20.6)||1.07 (0.21–5.37)||4.22 (1.80–9.88)†|
|Effusion||Yes vs. no||16.58 (2.22–2,120.5)§||37.46 (5.01–4,793.1)§||13.14 (1.72–1,687.8)§||2.85 (1.54–5.41)†|
|Bony swelling||Yes vs. no||1.78 (0.77–4.11)||4.12 (1.66–10.2)†||0.90 (0.37–2.20)||4.58 (2.52–8.33)†|
|Crepitus||Any vs. none||1.91 (0.87–4.18)||8.09 (2.89–22.7)†||1.04 (0.46–2.35)||7.77 (3.38–17.9)†|
|Anserine bursa tenderness||Yes vs. no||0.65 (0.30–1.40)||1.01 (0.44–2.33)||0.46 (0.20–1.04)||2.22 (1.22–4.05)†|
|Flexion, degrees||10.8¶||0.57 (0.33–1.00)||0.30 (0.15–0.61)†||0.92 (0.46–1.84)||0.32 (0.22–0.49)†|
|Flexion contracture, degrees||3.7¶||2.37 (1.50–3.73)†||4.96 (2.67–9.21)†||1.73 (1.05–2.85)†||2.87 (1.76–4.76)†|
It is of interest to note that significant variables for ROA compared with pre-ROA are not all the same as those for pre-ROA compared with no OA, and in some cases, the associations are opposite. For example, anserine bursa tenderness is associated with a trend toward a reduced prevalence of pre-ROA versus no OA (OR 0.46, 95% CI 0.20–1.04), but is associated with an increased risk of ROA versus pre-ROA. This is not surprising because anserine bursa tenderness is a periarticular pain syndrome that is likely contributing to the symptomatic status of the no OA group and is also a finding commonly seen in ROA. Also of note is the fact that with the small number of subjects with no OA, there are relatively larger ORs involving that group that are not significant, whereas relatively smaller ORs do show up as significant in the ROA versus pre-ROA comparison.
In this population-based cohort of middle-aged and elderly people with knee pain, MRI-based pre–radiographic knee OA was highly prevalent, affecting 49% of this cohort, whereas ROA affected 38%. We have demonstrated that several clinical findings are associated with cartilage defects on MRI. Specifically, age, abnormal gait, effusion, flexion contracture, and increased duration of regular sports activity after age 20 years were associated with cartilage defects on MRI. Age, BMI, pain frequency, pain duration, regular sports activity after age 20 years, history of severe knee injury, abnormal gait, effusion, bony swelling, crepitus, flexion, and flexion contracture were associated with ROA versus no OA. Age, regular sports activity after age 20 years, presence of effusion and flexion contracture, and absence of valgus malalignment were associated with pre-ROA versus no OA. All variables except one were significantly associated with ROA compared with pre-ROA.
Our findings are in keeping with findings from earlier studies that have evaluated clinical features in relation to prevalent radiographic disease (7, 8). An association of 14 of 18 clinical variables with ROA was reported by Claessens et al (7), including flexion pain, soft tissue swelling, bony enlargement, bony tenderness, effusion, and Heberden's nodes, as well as several variables on history. Peat et al (8) reported that effusion, crepitus, flexion contracture, and flexion ROM on physical examination together with other clinical variables such as age and BMI were useful for estimating the probability of ROA in a community sample of adults. However, both studies concluded that clinical variables were not sufficient as a diagnostic tool. Similarly, LaValley et al (9), who evaluated clinical historical variables, reported that ROA could not be diagnosed adequately using these features. In contrast, a recent study by Marra et al (22) found that a simple screening questionnaire administered by pharmacists could identify a large proportion of patients with knee pain who had undiagnosed knee OA based on the American College of Rheumatology clinical criteria (14). The majority of these patients had no evidence of radiographic knee OA, suggesting that clinical features may be able to detect earlier stages of disease. In a recent MRI study, Link et al (10) found higher WOMAC pain and function scores in subjects with cartilage lesions compared with those without cartilage lesions, although this study was limited to the radiographic stage of disease.
To our knowledge, our study is the first to evaluate the association of a broad range of clinical variables with OA using MRI-based determination of disease, and is the first to include the entire range of OA severity. We found that the risk of prevalent cartilage defects was increased with age, regular sports activity after age 20 years, and 3 knee examinations, including abnormal gait, effusion, and flexion contracture. This suggests that physical examination findings in combination with historical information may be more suitable for the identification of OA, as has been reported in previous research (8).
The result from our comparison of pre-ROA versus no OA highlights some differences that may relate to the earliest manifestations of disease or to the nonarticular nature of pain in those with no OA. Specifically, the findings of increased prevalence of pre-ROA compared with no OA with effusion and flexion contracture are novel. These may be subtle manifestations of early disease. In contrast, for anserine bursa tenderness, there was a trend toward a reduced prevalence of pre-ROA compared with no OA, suggesting that extraarticular sources of pain are contributing to the symptomatic status of subjects without OA. Similarly, valgus malalignment was associated with a reduced risk of pre-ROA compared with no OA. This finding is unexpected. It is not clear whether the higher prevalence of valgus malalignment in subjects without OA is a feature that contributes to pain in that group. It should be noted that malalignment was assessed clinically rather than on full-extremity radiographs. Although measurements from these two methodologies correlate highly (23), it is possible that the latter methodology would have yielded different results.
In our comparison of ROA with no OA, such extraarticular sources of pain were not of value to differentiate groups, likely related to the fact that those with ROA frequently experience anserine bursitis and may have other extraarticular sources of pain. However, other features that are usually thought of in relation to OA, such as age, pain frequency, pain duration, history of severe knee injury, effusion, bony swelling, crepitus, flexion, and flexion contracture, were clearly different in ROA compared with no OA.
There are some limitations to our study. Our study did not include an asymptomatic control group. As such, our findings are only applicable to symptomatic populations. However, the utility of clinical variables to differentiate symptomatic non-OA subjects from those with early or advanced OA is more important clinically, since subjects with pain are those likely to present to the health care professional. The agreement for quadriceps atrophy, crepitus, and bony swelling on knee examination was only moderate in this study, which may limit our ability to detect an association. In contrast, agreement for all other knee examinations was good, including gait, effusion, and flexion contracture, the 3 examinations associated with the presence of cartilage defects. Our findings of cartilage defects are based on MRI evaluations rather than arthroscopy as the gold standard. A further limitation is that our symptomatic control group was small. Although this limits the power to detect weaker associations, such weaker associations are less important clinically. Finally, a large number of analyses was performed, and this increases the likelihood that one or more associations may have occurred simply due to chance. However, as an early study in this field, our findings should serve as a guide for further research.
The strengths of this study include the evaluation of a population-based sample of subjects with knee pain. This allows for generalizability of our results to the population at large. Our study is unique in that it includes the full spectrum of knee OA severity, including established radiographic disease, early pre–radiographic disease, and symptomatic control subjects. The finding of historical as well as a broad range of physical examination variables in relation to MRI-based disease has not been previously reported, but might prove useful as a diagnostic tool and will require further development.
In conclusion, in this population-based cohort of people with knee pain, MRI-based cartilage defects were highly prevalent, affecting 87% of the cohort, with the majority of subjects (49%) having pre–radiographic disease and approximately one-third of subjects (38%) having ROA. We found that the risk of prevalent cartilage defects was significantly increased with age, regular adult sports activity, abnormal gait, effusion, and flexion contracture. Several clinical variables were associated with the subgroups of OA. The utility of these clinical variables for diagnostic purposes requires further validation.
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Cibere had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Cibere, Thorne, Wong, Singer, Kopec, Peterfy, Nicolaou, Esdaile.
Acquisition of data. Cibere, Guermazi, Peterfy, Nicolaou, Munk, Esdaile.
Analysis and interpretation of data. Cibere, Zhang, Thorne, Wong, Singer, Kopec, Guermazi, Peterfy, Nicolaou, Esdaile.
The authors thank all of the participants and staff of the Development of a Model for the Diagnosis of Early Knee Osteoarthritis Study.