SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. SUBJECTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Objective

To describe the association between prevalent and incident knee cartilage defects and loss of knee cartilage in male and female adults.

Methods

A convenience sample of 325 subjects (mean age 45 years; age range 26–61 years) was evaluated at baseline and ∼2 years later. Knee cartilage volume, cartilage defect scores (0–4 scale), and joint surface area were determined using T1-weighted fat-suppression magnetic resonance imaging techniques. Height, weight, and radiographic evidence of osteoarthritis were measured by standard protocols.

Results

Multivariable analysis revealed that baseline cartilage defect scores at the medial tibia, lateral tibia, and patella had a dose-response association with the annual rate of change in knee cartilage volume at the corresponding site (β = –1.3% to –1.2% per grade; P < 0.05 for all comparisons). In addition, an increase in knee cartilage defect score (change of ≥1) was associated with higher rates of knee cartilage volume loss at all sites (β = –1.9% to –1.7% per year; P < 0.01 for all comparisons). Furthermore, a decrease in the knee cartilage defect score (change of less than or equal to −1) was associated with an increase in knee cartilage volume at all sites (β = 1.0% to 2.7% per year; P < 0.05 for all comparisons).

Conclusion

Prevalent knee cartilage defects are predictive of compartment-specific cartilage loss over 2 years. Both increases and decreases in knee cartilage defects are associated with changes in knee cartilage volume, which implies a potential for reversal of knee cartilage loss.

Knee cartilage defects are commonly found by magnetic resonance imaging (MRI) in healthy subjects (1) and by arthroscopy in symptomatic subjects (2). The defects are thought to occur through sports injury, trauma, osteoarthritis (OA), and osteochondritis (3). Multiple treatments have been used to repair cartilage defects (3–6), based on the assumption that such defects will increase cartilage loss and will progress to OA (3). However, there is limited evidence to support this contention.

The prevalence and severity of chondral defects increase with increasing age (7), body mass index (BMI) (8), and genetic factors (9). In our recent cross-sectional study, we found that the severity and prevalence of knee cartilage defects were negatively associated with knee cartilage volume and were positively associated with urinary levels of the C-terminal crosslinking telopeptide of type II collagen, suggesting that knee cartilage defects may play a key role in cartilage loss (1). A smaller longitudinal study of healthy middle-age adults living in Melbourne, which was recently conducted by our group, suggested that baseline cartilage defects were associated with greater loss of cartilage from the medial tibial compartment, but not the lateral tibial compartment (10). This inconsistency may reflect the small sample size in the study, or it may reflect compartment-specific effects. An association between patellar cartilage defects at baseline and patellar cartilage loss has not been reported. Furthermore, it is unknown whether increases or decreases in knee cartilage defects lead to changes in cartilage volume. These uncertainties indicated the need to validate our findings in a larger independent sample.

MRI techniques can be used to visualize joint structures directly and noninvasively, and MRI is recognized as a valid, accurate, and reproducible tool with which to measure articular cartilage defects (1, 7–11) and cartilage volume (12–14). The aim of this longitudinal study, therefore, was to describe the association between prevalent and incident knee cartilage defects and knee cartilage loss in a convenience sample of male and female adults.

SUBJECTS AND METHODS

  1. Top of page
  2. Abstract
  3. SUBJECTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Study subjects.

The study was conducted in Southern Tasmania, primarily in the capital city of Hobart, from June 2000 until December 2001, and the followup evaluation was conducted ∼2 years later. Subjects were selected from 2 sources. One hundred sixty-two subjects were the adult children (offspring) of subjects who had undergone knee replacement surgery for primary knee OA at any Hobart hospital during the years 1996–2000. This diagnosis was confirmed by reference to the medical records of the orthopedic surgeon and the original radiograph where possible. One hundred sixty-three subjects were randomly selected controls. These subjects were selected by computer-generated random numbers from the most up-to-date version of the electoral roll at the time (for the year 2000).

Subjects were excluded from either group if they had contraindications for MRI, including metal sutures, shrapnel, iron filings in the eye, and claustrophobia. None of the women were taking hormone replacement therapy at the time of the study. This study was approved by the Southern Tasmanian Health and Medical Human Research Ethics Committee, and all subjects provided informed written consent.

Anthropometric assessments.

Weight was measured to the nearest 0.1 kg (with shoes, socks, and bulky clothing removed) using the same set of electronic scales (Seca Delta model 707) for all subjects and all assessments. Scales were calibrated using a known weight at the beginning of each clinic. Height was measured to the nearest 0.1 cm (with shoes and socks removed) using a stadiometer. The BMI (in kg/m2) was calculated for each study subject.

Radiographic assessment of the knee.

A standing, anteroposterior view of the right knee in semiflexed position was performed on all subjects at baseline. The presence of tibiofemoral radiographic OA was then assessed using the Altman atlas (15). Each of the following 4 features was scored individually on a scale of 0–3 (0 = normal and 3 = severe): medial joint space narrowing, lateral joint space narrowing, medial osteophytes (femoral and tibial combined), and lateral osteophytes (femoral and tibial combined). Each score was reached by consensus, with 2 readers (GJ and FS) simultaneously assessing the radiograph with immediate reference to the atlas. Reproducibility was assessed and yielded an intraclass correlation coefficient of 0.99 for osteophytes and 0.98 for joint space narrowing (16).

Measurement of knee cartilage volume.

MRI scans of the right knees were performed at baseline and followup. Knees were imaged in the sagittal plane with a 1.5T whole-body magnetic resonance unit (Picker, Cleveland, OH) using a commercial transmit–receive extremity coil. The following image sequence was used: a T1-weighted fat-suppressed 3-dimensional gradient-recall acquisition in the steady state, flip angle 55°, repetition time 58 msec, echo time 12 msec, field of view 16 cm, 60 partitions; 512 × 512–pixel matrix, acquisition time 11 minutes 56 seconds, and 1 acquisition. Sagittal images were obtained at a partition thickness of 1.5 mm and an in-plane resolution of 0.31 × 0.31 mm (512 × 512 pixels).

Knee cartilage volume was determined by means of image processing on an independent computer work station using Osiris software (University of Geneva, Geneva, Switzerland) as previously described (16–19). The volumes of individual cartilage plates (medial tibia, lateral tibia, and patella) were isolated from the total volume by manually drawing disarticulation contours around the cartilage boundaries on a section-by-section basis. These data were then resampled by means of bilinear and cubic interpolation (area of 312 × 312 μm and thickness of 1.5 mm, using continuous sections) for the final 3-dimensional rendering. The volume of the particular cartilage plate was then determined by summing all the pertinent voxels within the resultant binary volume. Femoral cartilage volume was not assessed in this study, since we have previously found that the 2 tibial sites and the patellar site correlate strongly with this site (20). There was high intraobserver and interobserver reproducibility with this method. The coefficient of variation for the 3 cartilage volume measures was previously determined to be 2.1% for the medial tibia, 2.2% for the lateral tibia, and 2.6% for the patella (17).

Measurement of knee bone size.

The tibial plateau bone area and the patellar bone volume were determined by means of image processing on an independent computer work station using Osiris software as previously described (1, 16, 17). To transform the images to the axial plane, the Analyze software package developed by the Mayo Clinic (Rochester, MN) was used. The bone area of the medial and lateral tibial plateau is uniform in nature and was directly measured from the reformatted axial images. Total volume was calculated for the patellar bone because of its irregular shape, which made it difficult to identify a simpler, representative measure of patellar size. The coefficients of variation for these measures in our experience are 2.2–2.6% (17).

Cartilage defect assessments.

Cartilage defects identified on 2 sagittal MRI scans (obtained on 2 different occasions) of the medial tibia, lateral tibia, and patella were graded as previously described (1), using a 0–4 scale, where 0 = normal cartilage, 1 = focal blistering and an intracartilaginous area of low signal intensity, with an intact surface and bottom, 2 = irregularities on the surface or bottom and a <50% loss of thickness, 3 = deep ulceration, with a >50% loss of thickness, and 4 = full-thickness chondral wear, with exposure of the subchondral bone. Cartilage was considered normal if the band of intermediate signal intensity had a uniform thickness. One month later, the cartilage defects were graded a second time, and the average scores for cartilage defects at the medial tibia, lateral tibia, and patella (average score for each site 0–4) were used in the study.

The intraobserver reliability (expressed as the intraclass correlation coefficient) was previously determined to be 0.89–0.94, and the interobserver reliability was 0.85–0.93 (1). Changes in cartilage defects were calculated by subtracting the cartilage defect scores at baseline from the cartilage defect scores at followup. A change in the cartilage defect score of ≥1 was defined as an increase in cartilage defects, and a change in the cartilage defect score of less than or equal to –1 was defined as a decrease in cartilage defects (Figure 1). We chose these levels of change because they are in excess of the least significant change in an individual as calculated by a standard formula (see below). All of the increases and decreases in knee cartilage defect scores were confirmed by paired readings in 150 of the study subjects.

thumbnail image

Figure 1. Change in knee cartilage defects over 2 years in 2 different subjects. A, In this subject, the patellar cartilage defect (long arrow) is grade 2 at baseline and grade 4 at followup. The tibial cartilage defect (short arrow) is grade 1 at baseline and grade 0 at followup. B, In this subject, the tibial cartilage defect (arrow) is grade 3 at baseline and grade 1 at followup.

Download figure to PowerPoint

Statistical analysis.

Rates of change in cartilage volume were calculated in 2 ways. The absolute change per year was calculated as follows:

  • equation image

The percentage change per year was calculated as follows:

  • equation image

To account for measurement error regarding the significance of individual changes, the least significant criterion (LSC) was used. Due to high within-subject correlation for knee cartilage volume (all >0.93), the most appropriate formula was as follows:

  • equation image

where σi2 is the within-subject variance and ρi is the correlation between serial measurements. A significant loss in cartilage volume was defined as a decrease in cartilage volume greater than the LSC at that site (21).

Linear regression analysis was used to examine the associations between the percentage loss per year and the knee cartilage defects at baseline or the change in cartilage defects before and after adjustment for age, sex, BMI, offspring/control status, tibiofemoral radiographic OA, baseline cartilage volume, past knee injury, and bone size. Logistic regression analysis was used to examine the associations between significant cartilage loss (significant cartilage loss versus no significant cartilage loss) and baseline knee cartilage defects or incident cartilage defects both before and after adjustment.

Residuals from the regression of cartilage loss, the baseline cartilage defect score, or changes in cartilage defect scores on age, sex, BMI, offspring/control status, and respective cartilage volume and bone size represent the component of cartilage loss or defect score not explained by these factors (13). We added to these residuals the mean cartilage loss, baseline defect score, or changes in cartilage defect scores for the respective joint site and plotted these “adjusted” cartilage loss values against the “adjusted” baseline cartilage defect score (0 if adjusted score was <0.5, 1 if adjusted score was ≥0.5 but <1.5, 2 if adjusted score was ≥1.5 but <2.5, 3 if adjusted score was ≥2.5 but <3.5, and 4 if adjusted score was ≥3.5) or against the “adjusted” changes in cartilage defect scores (–2 if adjusted score was less than –1.5, –1 if adjusted score was greater than or equal to –1.5 but less than –0.5, 0 if adjusted score was greater than or equal to –0.5 but less than 0.5, 1 if adjusted score was greater than or equal to 0.5 but less than 1.5, and 2 if adjusted score was greater than or equal to 1.5) for the respective joint site. The result of these manipulations was to achieve a defect score that had been adjusted for important covariates. P values less than 0.05 (2-tailed) or 95% confidence intervals not including the null point were regarded as statistically significant. All statistical analyses were performed with SPSS software (version 12.0 for Windows; SPSS, Chicago, IL).

RESULTS

  1. Top of page
  2. Abstract
  3. SUBJECTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

A total of 325 subjects (135 men and 190 women) completed the study (87% of those originally evaluated). This was a young sample, with an average age of 45 years at baseline (age range 26–61 years). Characteristics of the study subjects are presented in Table 1. Knee cartilage defects were common, varying from grade 1 to grade 4, but the mean defect score at each site was low. After an average of 2.3 years, the patellar cartilage defect score increased significantly (P < 0.01), whereas there were no significant changes in cartilage defect scores at the other 2 sites (P >0.05). However, 12%, 13%, and 22% of subjects had an increase in cartilage defect scores, whereas 13%, 12%, and 13% of subjects had a decrease in cartilage defect scores at the medial, lateral, and patellar sites, respectively. Knee cartilage volume decreased significantly from baseline (P < 0.001 for each site), with the annual rate of loss varying from 1.5% to 4.2%. There were 50%, 49%, and 71% of subjects who had significant cartilage loss at the medial tibial, lateral tibial, and patellar sites, respectively. There were 22%, 35%, and 10% of subjects who had an absolute increase in knee cartilage volume at the medial tibial, lateral tibial, and patellar sites, respectively.

Table 1. Characteristics of the study participants*
 Total (n = 325)Men (n = 135)Women (n = 190)
  • *

    Cartilage defects were scored on a scale of 0–4 (see Subjects and Methods for details). Except where indicated otherwise, values are the mean ± SD. BMI = body mass index.

Age, years45.2 ± 6.545.0 ± 6.545.3 ± 6.4
Height, cm169.0 ± 8.4176.0 ± 6.5164.1 ± 5.6
Weight, kg77.4 ± 15.384.6 ± 12.672.3 ± 15.1
BMI, kg/m227.0 ± 4.827.3 ± 3.726.9 ± 5.4
Past knee injury, %193111
Radiographic osteoarthritis, %181619
Medial tibial bone area, cm217.3 ± 2.719.8 ± 2.215.8 ± 1.7
Lateral tibial bone area, cm212.0 ± 2.013.6 ± 1.810.8 ± 1.3
Patellar bone volume, ml13.7 ± 3.316.5 ± 2.811.8 ± 2.1
Cartilage volume, ml   
 Medial tibia2.2 ± 0.52.6 ± 0.51.9 ± 0.4
 Lateral tibia2.6 ± 0.73.1 ± 0.62.2 ± 0.4
 Patella3.4 ± 1.04.2 ± 0.92.9 ± 0.7
Annual loss of cartilage volume, ml   
 Medial tibia0.06 ± 0.100.06 ± 0.110.06 ± 0.09
 Lateral tibia0.04 ± 0.090.05 ± 0.100.04 ± 0.09
 Patella0.15 ± 0.150.20 ± 0.170.12 ± 0.12
Annual loss of cartilage, %   
 Medial tibia2.5 ± 4.12.1 ± 4.22.8 ± 4.0
 Lateral tibia1.5 ± 3.41.4 ± 3.31.6 ± 3.5
 Patella4.2 ± 3.84.6 ± 4.04.0 ± 3.7
Cartilage defect score at baseline   
 Medial tibia1.2 ± 0.41.2 ± 0.51.2 ± 0.4
 Lateral tibia1.2 ± 0.41.2 ± 0.51.1 ± 0.4
 Patella1.2 ± 1.01.0 ± 0.91.4 ± 1.1
Change in cartilage defect score at followup   
 Medial tibia−0.06 ± 0.860.13 ± 0.87−0.20 ± 0.83
 Lateral tibia−0.04 ± 0.870.05 ± 0.86−0.11 ± 0.87
 Patella0.12 ± 0.730.10 ± 0.740.12 ± 0.71

In individual compartments, baseline cartilage defect scores were significantly associated with the rate of annual cartilage volume loss at the medial tibial, lateral tibial, and patellar sites after adjustment for confounders (Table 2). In women, baseline cartilage defect scores were significantly associated with the rate of annual cartilage volume loss at all sites, but only the patellar baseline cartilage defect scores were significantly associated with the rate of annual patellar cartilage volume loss in men (Figure 2). Changes in cartilage defect scores were also strongly associated with the rate of annual cartilage volume loss before and after adjustment for confounders in the total sample (Table 2), as well as in men and women separately (Figure 3).

Table 2. Association between knee cartilage defects and annual rate of change in cartilage volume (%), by site
 Univariable analysis β (95% CI)Multivariable analysis β (95% CI)*P
  • *

    Adjusted for age, sex, body mass index, offspring/control status, baseline cartilage volume, baseline bone size, and/or radiographic osteoarthritis. 95% CI = 95% confidence interval.

  • Statistically significant.

Change in medial tibial cartilage   
 Baseline defects, per grade−0.17 (−1.19, +0.85)−1.15 (−2.21, −0.09)0.034
 Change in defects, per grade−1.49 (−1.99, −0.99)−1.15 (−1.67, −0.63)<0.001
 Increase in defects, yes versus no−2.80 (−3.86, −1.75)−1.75 (−2.77, −0.72)0.001
 Decrease in defects, yes versus no+2.18 (+1.18, +3.17)+1.59 (+0.62, +2.56)0.001
Change in lateral tibial cartilage   
 Baseline defects, per grade−0.88 (−1.77, +0.01)−1.20 (−2.09, −0.31)0.009
 Change in defects, per grade−0.99 (−1.41, −0.56)−0.96 (−1.34, −0.54)<0.001
 Increase in defects, yes versus no−2.08 (−2.99, −1.16)−1.65 (−2.55, −0.75)<0.001
 Decrease in defects, yes versus no+1.07 (+0.20, +1.94)+0.99 (+0.13, +1.85)0.024
Change in patellar cartilage   
 Baseline defects, per grade−0.47 (−0.89, −0.06)−1.32 (−1.78, −0.85)<0.001
 Change in defects, per grade−1.66 (−2.21, −1.11)−1.79 (−2.31, −1.27)<0.001
 Increase in defects, yes versus no−2.04 (−3.03, −1.05)−1.92 (−2.84, −1.00)<0.001
 Decrease in defects, yes versus no+2.45 (+1.24, +3.67)+2.65 (+1.50, +3.80)<0.001
thumbnail image

Figure 2. Box plots of the annual change in cartilage volume (%) at the medial tibia, the lateral tibia, and the patella versus the corresponding cartilage defect score at baseline in A, men and B, women. Each box represents the 25th to 75th percentiles (interquartile range [IQR]). Lines inside the boxes represent the median. Vertical bars represent 1.5 times the IQR. Circles represent outliers. Data were adjusted for age, body mass index, offspring/control status, baseline cartilage volume, baseline bone size, and/or radiographic osteoarthritis, using residuals from the regression models and adding these to the mean cartilage volume change or change in defect scores. P values were determined after adjustment for the covariates.

Download figure to PowerPoint

thumbnail image

Figure 3. Box plots of the annual change in cartilage volume (%) at the medial tibia, the lateral tibia, and the patella versus the corresponding change in cartilage defect score at followup in A, men and B, women. Each box represents the 25th to 75th percentiles (interquartile range [IQR]). Lines inside the boxes represent the median. Vertical bars represent 1.5 times the IQR. Circles represent outliers. Data were adjusted for age, body mass index, offspring/control status, baseline cartilage volume, baseline bone size, and/or radiographic osteoarthritis, using residuals from the regression models and adding these to the mean cartilage volume change or change in defect scores. P values were determined after adjustment for the covariates.

Download figure to PowerPoint

When groups were split according to an increase or a decrease in cartilage defects, we found that increases in cartilage defects were positively associated, and decreases in cartilage defects were negatively associated, with the rate of annual cartilage loss before and after adjustment for confounders (Table 2). Increases in knee cartilage defect scores were all significantly associated with the rate of annual cartilage volume loss in women (medial tibia β = –1.51 [P = 0.03], lateral tibia β = –1.66 [P = 0.009], and patella β = –2.23 [P < 0.001]), with similar trends but borderline significant results in men (medial tibia β = –1.59 [P = 0.053], lateral tibia β = –1.68 [P = 0.014], and patella β = –1.40 [P = 0.079]). Furthermore, a decrease in knee cartilage defect scores was significantly associated with an increase in cartilage volume at all sites in men (medial tibia β = +2.98 [P = 0.001], lateral tibia β = +1.53 [P = 0.036], and patella β = +3.99 [P < 0.001]), but with inconsistent results in women (medial tibia β = +1.11 [P = 0.055], lateral tibia β = +0.55 [P = 0.33], and patella β = +1.71 [P = 0.018]).

Consistent associations were observed between prevalent and incident knee cartilage defects and significant cartilage loss in the whole sample (Table 3), with similar trends in men and women. When offspring and controls were analyzed separately or when subjects with tibiofemoral radiographic OA were excluded from the analyses, similar results were obtained (data not shown). Results remained unchanged after adjustment for past knee injury (data not shown).

Table 3. Association between knee cartilage defects and significant loss of cartilage, by site
 Univariable analysis OR (95% CI)Multivariable analysis OR (95% CI)*P
  • *

    Adjusted for age, sex, body mass index, offspring/control status, baseline cartilage volume, baseline bone size, and/or radiographic osteoarthritis. OR = odds ratio; 95% CI = 95% confidence interval.

  • Statistically significant.

Significant loss of medial tibial cartilage   
 Baseline defects, per grade1.26 (0.76, 2.09)2.48 (1.20, 5.14)0.015
 Change in defects, per grade1.88 (1.42, 2.49)1.59 (1.13, 2.23)0.008
 Increase in defects, yes versus no3.31 (1.84, 5.94)1.89 (1.00, 3.62)0.05
 Decrease in defects, yes versus no0.43 (0.25, 0.72)0.51 (0.27, 0.96)0.036
Significant loss of lateral tibial cartilage   
 Baseline defects, per grade1.94 (1.12, 3.36)2.35 (1.17, 4.71)0.017
 Change in defects, per grade1.59 (1.21, 2.09)1.61 (1.18, 2.20)0.002
 Increase in defects, yes versus no2.54 (1.44, 4.50)2.27 (1.21, 4.24)0.01
 Decrease in defects, yes versus no0.60 (0.36, 1.00)0.56 (0.31, 1.00)0.05
Significant loss of patellar cartilage   
 Baseline defects, per grade0.87 (0.68, 1.10)1.93 (1.31, 2.84)0.001
 Change in defects, per grade2.33 (1.60, 3.38)2.78 (1.76, 4.42)<0.001
 Increase in defects, yes versus no3.33 (1.58, 7.03)3.22 (1.40, 7.45)0.006
 Decrease in defects, yes versus no0.38 (0.20, 0.74)0.34 (0.15, 0.75)0.008

DISCUSSION

  1. Top of page
  2. Abstract
  3. SUBJECTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

In this study, we demonstrated consistent and significant associations between knee cartilage defects and knee cartilage loss in a relatively young population. Baseline cartilage defect scores were associated with higher cartilage loss at the medial tibial site, which is consistent with the findings of our previous study (10). However, this study is the first to demonstrate that baseline cartilage defect scores are associated with higher cartilage loss in the lateral tibial and patellar sites. These findings suggest that knee cartilage defects are predictive of knee cartilage loss over 2 years. Furthermore, this study is also the first to demonstrate that both increases and decreases in knee cartilage defect scores are associated with changes in cartilage volume.

Knee cartilage defects assessed by MRI are highly comparable to findings of arthroscopic (22–24) and histologic (25) assessments and have been significantly associated with radiographic evidence of knee OA (11, 26) as well as with knee pain (27). In our previous cross-sectional study (1), we found that knee cartilage defects are common, with 44% of our subjects having cartilage defects of grade 2 or more at any site of the knee. The prevalence and severity of knee cartilage defects increase with increasing risk factors for OA, such as increasing age (7) and BMI (8), and are significantly associated with tibiofemoral osteophytes, increased tibial bone area, decreased knee cartilage volume, and increased urine levels of a type II collagen biomarker that may reflect hyaline cartilage breakdown (1). This suggests an important role for knee cartilage defects in early knee OA.

We recently reported an association between knee cartilage defects and medial tibial cartilage loss in healthy middle-age adults, but the sample size in that study was small, and the association in the lateral compartment was not significant (10). However, this may represent a compartment-specific effect, since OA is much more common in the medial compartment. There have been no previous reports of an association between baseline cartilage defects and patellar cartilage loss. In this longitudinal study, we found that the rate of cartilage loss increased by 1.2–1.3% per year per grade of baseline cartilage defects in a dose-response manner, suggesting that knee cartilage defects are precursors of knee cartilage loss and are relevant in all knee compartments. The results were independent of baseline cartilage volume, bone size, risk factors for OA (sex, age, and BMI), past knee injury, and tibiofemoral radiographic OA itself, suggesting a direct link. When our analyses were repeated excluding those with tibiofemoral radiographic OA, the magnitude or direction of our findings did not change, suggesting that the findings are unlikely to be due to significant tibiofemoral radiographic OA, but it remains possible that they reflect early pathophysiologic changes of OA.

The relationship between change in knee cartilage defects and knee cartilage loss has not previously been reported, although an increase in knee cartilage defect score is often defined as cartilage loss (28, 29). However, a change in cartilage defects, as measured in our study, does not account for the much larger change in cartilage volume we observed. These are not necessarily the same process, and therefore, they do not have to directly correspond. Indeed, in the current study, there was no significant change in cartilage defect score overall, whereas there was an overall decrease in cartilage volume. Furthermore, the scoring of volume is fully quantitative, while the scoring of defects is semiquantitative and, thus, cannot be as accurate. Knee cartilage defects are not static (28). A recent report suggested that increases in knee cartilage defects were associated with a loss of joint space over a period of 30 months in subjects with symptomatic OA (29); however, joint space measurements on radiographs do not measure cartilage alone, since the radiographic joint space includes the menisci and is dependent on positioning of the knee.

In the present study, we found that changes in knee cartilage defects were significantly and strongly associated with changes in knee cartilage volume in all 3 compartments. For every increase in the grade of change in cartilage defect scores, the annual loss of cartilage increased by 1.0–1.8% and the significant cartilage loss increased 1.6–2.8-fold. Moreover, increases in knee cartilage defects over 2.3 years were associated with 1.7–1.9% per year higher cartilage loss and 1.9–3.2-fold higher significant cartilage loss in all 3 knee compartments. This most likely reflects a real change in cartilage volume, since volume averaging or the presence of focal and non–full-thickness cartilage defects itself has little effect on the overall volume measurement. The magnitude of this loss is substantial. For example, it can be estimated from the data in Table 2 that subjects with a stable grade 3 medial tibial defect will lose 60% of their cartilage, which represents end-stage OA (30, 31), in 17 years.

In this sample, 12–13% of the subjects had a decrease in knee cartilage defects in each of the individual compartments. Although this may be due to partial volume averaging, it seems unlikely, since to minimize this possibility, we required that defects had to be present on 2 consecutive slices. The decrease in cartilage defects may therefore represent cartilage repair and healing, since it was greater than what would be expected due to measurement error alone. We further found that decreases in knee cartilage defects were associated with increases in knee cartilage volume. While interventions such as weight loss (Ding C, et al: unpublished observations), surgical treatment (3, 4), and gene therapy (5, 6) can improve knee cartilage defects, the results of our study suggest that knee cartilage defects are potential targets for reversing the loss of knee cartilage.

The association between baseline cartilage defects and annual cartilage loss was more consistent in women, which may suggest that women with knee cartilage defects are more susceptible to cartilage loss. In contrast, the association between a decrease in knee cartilage defects and an increase in knee cartilage volume was more consistent in men, which suggests that men who have a decrease in knee cartilage defects are more likely to gain cartilage volume. This variability may reflect actual sex differences due to differences in sex hormones, joint loading, or size, or, more likely, it reflects random statistical variation due to sample size issues. Overall, the results are more consistent than inconsistent across the sexes, but even larger studies will be required to resolve these inconsistencies.

There are several potential limitations of this study. First, the study was primarily designed to examine genetic mechanisms of knee OA and used a matched design. The matching was broken for the current study, but adjustment for family history did not alter the results. Indeed, while there was a reduction in power, the results otherwise did not differ when examined separately in offspring and controls, showing similar associations in these two groups. While the study population is a convenience sample, Miettinen (32) states that for associations to be generalizable to other populations, 3 key criteria need to be met: selection (inclusion/exclusion criteria for both offspring and controls are explicitly defined), sample size, and adequate distribution of study factors. All of them were met by our study.

Second, measurement error may have influenced the results. However, scoring of knee cartilage defects and measurements of volume, bone size, and tibiofemoral radiographic OA were highly reproducible, suggesting that measurement error is unlikely.

Third, we used tibial cartilage, rather than femoral cartilage, as the measure of joint cartilage at the tibiofemoral joint. However, we have previously shown both in cross-sectional (33) and longitudinal (20) studies a strong correlation between the tibial and femoral cartilage in the medial and lateral tibiofemoral compartments. Since the femoral cartilage articulates with 3 joints (the medial and lateral tibiofemoral and the patellofemoral joints), it is more difficult to clearly identify the relevant component of the femoral joint when assessing the medial and lateral tibiofemoral joints, since this requires arbitrary definitions. In contrast, each of the tibial cartilage plates examined in this study forms only part of 1 joint (either the medial or the lateral tibiofemoral joint).

Fourth, knee alignment is associated with the rate of knee cartilage loss (34); thus, the absence of leg alignment data (varus/valgus) in this study represents a potential limitation for the interpretation of these data. Last, we did not have patellofemoral radiographic views in this study, so we cannot comment on the influence of patellofemoral radiographic OA.

In conclusion, the findings of this longitudinal study suggest that prevalent knee cartilage defects are predictive of compartment-specific cartilage loss over 2 years at all sites in women and at the patellar site in men, whereas both increases and decreases in knee cartilage defects are associated with changes in knee cartilage volume, which implies a potential for the reversal of knee cartilage loss.

Acknowledgements

  1. Top of page
  2. Abstract
  3. SUBJECTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

A special thanks to the study subjects and the orthopedic surgeons who made this study possible. We would also like to thank Martin Rush for performing the MRI scans and Kevin Morris for technical support.

REFERENCES

  1. Top of page
  2. Abstract
  3. SUBJECTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES