Abstract
Background:
Focal chondral defects (FCDs) of the knee are believed to contribute to the development of osteoarthritis (OA), resulting in pain and dysfunction.
Purpose:
To investigate whether untreated FCDs of the knee progress to radiographically evident OA over time.
Study Design:
Systematic review; Level of evidence, 3.
Methods:
A literature review was performed by searching the PubMed, Embase, and Cochrane Library databases to locate studies evaluating clinical and/or radiological outcomes of patients with FCDs that were diagnosed by arthroscopic surgery or magnetic resonance imaging (MRI) and were left untreated with a minimum 2-year follow-up. Additionally, studies were included if there was a radiographic assessment of OA. Search terms used were “knee,” “focal,” “isolated,” “chondral,” “cartilage,” and “osteoarthritis.” Studies were evaluated based on clinical/radiological outcomes and OA risk factors. The study methodology was assessed using the modified Coleman Methodology Score.
Results:
Eight studies comprising 1425 knees met the inclusion criteria. All studies were of level 3 evidence. The risk of incident cartilage damage (enlargement of original FCDs or incidence of additional FCDs) at latest follow-up was assessed in 3 studies, while 1 study only reported the incidence of cartilage damage at follow-up. All 4 studies noted an increased progression of cartilage damage at follow-up. The progression of cartilage damage was most commonly seen in the patellofemoral joint and medial femoral condyle but was not associated with the development of knee OA based on the Kellgren-Lawrence grade. MRI of the FCDs revealed increased water content, cartilage deterioration, and proteoglycan loss within the medial and lateral compartments.
Conclusion:
Patients with untreated FCDs of the knee joint are more likely to experience a progression of cartilage damage, although the studies included in this review did not demonstrate the development of radiographically evident OA within 2 years of follow-up.
Focal chondral defects (FCDs) of the knee joint are common, occurring in over 60% of patients undergoing knee arthroscopic surgery. 1,7,9,13,18,26 FCDs have limited regenerative potential in response to injuries, as articular cartilage is relatively avascular and aneural. 12,13,26 Untreated FCDs within the knee joint can result in mechanical symptoms that impair function or cause pain and effusion, especially when located on weightbearing surfaces of the medial or lateral compartments. 13 In contrast, osteoarthritis (OA) of the knee joint is characterized by progressive loss of articular cartilage, osteophytes, subchondral cysts, joint space narrowing, and intermittent inflammation of the joint tissues. 30,32 Because FCDs can be seen in both radiographically healthy knees and arthritic knees, detecting their presence and progression is important for monitoring the natural disease course of these defects. 5,10,15 Some believe that FCDs progress to OA and cause permanent knee deterioration. 30 To date, there is a lack of knowledge regarding the correlation between the presence of an isolated FCD and possible eventual progression to OA. The purpose of this review was to determine if untreated FCDs of the knee joint result in radiographically evident OA changes within 2 years or if no such association exists.
Methods
Literature Search
A literature review of multiple databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two independent reviewers searched PubMed, Embase, and the Cochrane Library up to October 9, 2017. The electronic search strategy used was the following: knee AND (focal OR isolated) AND (chondral OR cartilage) AND osteoarthritis. A total of 2512 studies were reviewed by title and/or abstract to determine study eligibility based on inclusion and exclusion criteria. Inclusion criteria included (1) studies that reported clinical and/or radiological outcomes of patients with untreated FCDs, (2) a radiological or arthroscopic diagnosis of FCDs, (3) studies that reported clinical and radiological outcomes with a minimum 2-year follow-up, and (4) studies that reported a radiographic assessment of OA. Exclusion criteria included (1) non-English publications, (2) studies unrelated to the knee, (3) patients with FCDs who underwent surgical treatment, and (4) studies with no radiographic assessment of OA at follow-up. Eight studies were determined to meet inclusion and exclusion criteria (Figure 1).
The electronic search strategy is outlined using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. FCD, focal chondral defect; OA, osteoarthritis.
Reporting Outcomes
Radiographic and magnetic resonance imaging (MRI) scores, clinical outcome scores, and OA risk factors were recorded. Baseline OA risk factors included knee symptoms (pain, aching, or stiffness in or around the knee, or frequent use of pain medication for at least 1 month but not most days in the past 12 months), overweight or obesity, prior knee injury, prior knee surgery, history of knee replacement in a parent or sibling, Heberden nodes, frequent knee bending (repetitive activities involving bending, squatting, kneeling, climbing, or lifting), or radiographic OA (Kellgren-Lawrence grade ≥2). 16,20 Overweight was defined as a body mass index (BMI) between 25 and 29.9 kg/m2, and obesity was defined as a BMI ≥30 kg/m2. 20
Study Methodology
The Modified Coleman Methodology Score (MCMS) was used to evaluate study methodology quality. 8 The MCMS has a scaled potential score ranging from 0 to 100. Scores ranging from 85 to 100 are excellent, 70 to 84 are good, 55 to 69 are fair, and <55 are poor.
Statistical Analysis
For continuous variables, means and SDs were calculated. Categorical variables were totaled and reported as percentages. Because of the significant heterogeneity of the included studies, statistical comparisons could not be made, and therefore, the data were primarily descriptive.
Results
Literature Search
Eight studies 2, 11, 15, 20,28 –31 met the inclusion and exclusion criteria (all level 3 evidence). Table 1 shows the MCMS values from the 8 included studies. Five studies achieved a good score, 11,15,20,29,30 while 3 studies achieved a fair score. 2,28,31 The mean score was 70.9 ± 3.7.
Modified Coleman Methodology Scores
Patient and Lesion Characteristics
Table 2 depicts the patient demographics from the included studies. A total of 1425 knees were included. The mean patient age was 47.6 ± 13.9 years, with a mean BMI of 26.8 ± 2.7 kg/m2. The minimum follow-up ranged from 24 months 2,15 to 158.4 months. 30 Overall, there were a total of 1851 chondral lesions, 682 meniscal lesions, and 745 bone marrow lesions (BMLs) (Table 3). Table 4 presents the OA risk factors met by patients in the included studies.
Population Demographics a
a BMI, body mass index; ICRS, International Cartilage Repair Society 6 ; NR, not reported; OB, Outerbridge classification; WORMS, Whole-Organ Magnetic Resonance Imaging Score.
Baseline Lesion Characteristics a
a BML, bone marrow lesion; ICRS, International Cartilage Repair Society 6 ; LA, lateral anterior; LB, lateral body; LFC, lateral femoral condyle; LP, lateral posterior; LTFJ, lateral tibiofemoral joint; LTP, lateral tibial plateau; MA, medial anterior; MB, medial body; MFC, medial femoral condyle; MP, medial posterior; MTFJ, medial tibiofemoral joint; MTP, medial tibial plateau; Multi, multiple locations; NR, not reported; OB, Outerbridge classification; P, patella; PFJ, patellofemoral joint; T, trochlea; TFJ, tibiofemoral joint; WORMS, Whole-Organ Magnetic Resonance Imaging Score.
Baseline Osteoarthritis Risk Factors (n = 1167 Patients) a
a “+” indicates that the risk factor was present but that no exact number was available. BMI, body mass index, NR, not reported.
b Repetitive activities involving bending, squatting, kneeling, climbing, or lifting.
c Kellgren-Lawrence grade ≥2.
A wide variety of imaging assessment tools was used in each of the studies (Table 5). The most commonly used imaging parameters were the Kellgren-Lawrence grade 19 (all 8 studies), the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) 25 (5 studies 2,15,20,28,29 ), and MRI T2 values (4 studies 2,11,20,31 ). The most commonly used outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 3 (Table 6).
Imaging Assessment Tools a
a “+/–” indicates that the outcome measure was/was not performed. BMEP, bone marrow edema pattern; dGEMRIC, delayed gadolinium-enhanced magnetic resonance imaging of cartilage; ICRS, International Cartilage Repair Society 6 ; KL, Kellgren-Lawrence; OB, Outerbridge classification; WORMS, Whole-Organ Magnetic Resonance Imaging Score.
Outcome Measures Used a
a “+/–” indicates that the outcome measure was/was not performed. KOOS, Knee Injury and Osteoarthritis Outcome Score; PASE, Physical Activity Scale for the Elderly; VAS, visual analog scale for physical function; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.
Three studies 2,20,29 examined middle-aged patients (45-55 years old) with OA risk factors, such as history of knee injury or surgery, but no radiographic OA from the Osteoarthritis Initiative (OAI) database. Two studies 15,28 assessed patients aged 50 to 79 years at baseline with or at high risk for knee OA using participants from the Multicenter Osteoarthritis Study (MOST). Of the 5 multicenter studies, 2,15,20,28,29 3 studies 15,28,29 reported the risk of incident cartilage defects, while 1 study 20 only reported the incidence of cartilage damage at follow-up (Table 7).
Risk for Incident Cartilage Damage at Latest Follow-up a
a The reference group for 2 studies 15,28 was patients with no cartilage damage (WORMS = 0) at baseline, while the reference group for 1 study 29 was patients without FKB. BMI, body mass index; FKB, frequent knee bending; inf, infinity; NR, not reported; OR, odds ratio; PFJ, patellofemoral joint; TFJ, tibiofemoral joint; WORMS, Whole-Organ Magnetic Resonance Imaging Score.
b Statistical significance (P < .05) between the study groups.
c Statistical significance (P < .05) between the study group and reference group.
One of the MOST studies 15 found that patients with baseline partial- and full-thickness FCDs had a significantly higher risk of incident cartilage damage in other subregions within the same compartment of the tibiofemoral joint (TFJ), regardless of depth, over a 30-month follow-up. This study also found that partial- and full-thickness defects are similarly relevant to the development of cartilage damage in the OA disease process. 15 Another MOST study 28 found that compared to knees without full-thickness cartilage damage, those with isolated TFJ or patellofemoral joint (PFJ) full-thickness damage had 2.7 and 5.8 times the odds, respectively, of developing mixed full-thickness cartilage damage. Similarly, compared to patients without any BMLs, those with isolated TFJ or PFJ BMLs had 4.2 and 5.4 times the odds, respectively, of developing mixed BML damage. 28 Interestingly, this study found that in most knees that developed cartilage damage in multiple compartments, the damage was initially isolated to the PFJ at 7-year follow-up. 28 One study 29 found that patients who participated in frequent knee bending had a significantly higher risk of incident cartilage lesions, especially in the PFJ compartment, and had an increased risk of overall progression of cartilage damage and meniscal abnormalities over 36 months. Another study 20 found a statistically significant progression in the number of knees with cartilage lesions of any grade in obese patients over a 36-month follow-up. However, obesity did not increase the relative risk of the progression of meniscal lesions or high-grade cartilage defects (Table 7). This study 20 suggested that this finding may be because of lower activity levels of very obese people.
Using data from the OAI database, Baum et al 2 demonstrated that neither the presence of OA risk factors nor the presence of cartilage lesions at baseline were associated with increases in cartilage T2 values at 24-month follow-up. However, significantly increased cartilage T2 values were seen in the medial femoral condyle (MFC) of patients with OA risk factors. Additionally, patients with cartilage lesions had significantly higher T2 values compared to patients without cartilage lesions at both baseline and 24 months, but there was no accelerated T2 increase over 24 months. Furthermore, this study suggested that because elevated T2 values indicate increased water content and deterioration of the collagen network, 4,21 elevated T2 values may be a more sensitive biomarker for cartilage degeneration in the initial stages of OA. 2,24
In a natural history study by Engen et al, 11 the authors evaluated the articular cartilage of 11 patients with untreated FCDs and 10 patients with FCDs that were treated with cartilage repair at a mean 12-year follow-up. Uninjured knees served as a control group. While there were no significant differences in delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) values between groups, this study found degenerative changes (Kellgren-Lawrence grade >0) in 13 of the 21 knees. However, these changes did not correlate with cartilage quality assessed using dGEMRIC and T2 values. The authors concluded that there were no more degenerative changes in the injured knees than in the uninjured knees based on dGEMRIC.
At a mean follow-up of 15.3 years, Widuchowski et al 30 found that among young, active patients with a single FCD on the weightbearing surface of the TFJ, tibiofemoral OA with coexisting patellofemoral involvement was common. However, there was no correlation between the presence of an FCD and coexisting OA when the FCD was located on the patella. Additionally, in patients with an FCD within the TFJ, there was no correlation between clinical outcome scores and lesion size, whereas in patients with an FCD in the patella, a significant negative correlation was observed in each outcome score. OA changes were found in 39% of the patients, with no difference in OA severity between knees with a full-thickness FCD and an uninjured knee. This study concluded that severe FCDs with no treatment have a limited influence on clinical outcomes and the development of OA. 30 Finally, Williams et al 31 found that in patients with partial-thickness cartilage lesions, cartilage thickness within the TFJ decreased by 0.85% per year and that the most significant change was seen within the MFC, which decreased by 2.43% per year over a mean follow-up of 37 months.
Discussion
This review of the literature is the first to investigate if untreated FCDs of the knee joint progress to OA or if no such association exists. Based on this review, patients with untreated FCDs are more likely to experience a progression of cartilage damage within the same joint compartment, especially when located in the PFJ and on the MFC. This is apparent based on the radiological findings at follow-up, which have demonstrated an increased incidence of cartilage damage and worsening T2 and dGEMRIC values. Additionally, more specific MRI analyses have demonstrated increased water content and deterioration of the collagen network as well as tissue swelling due to proteoglycan loss in patients with FCDs within the TFJ. These findings may be associated with the cartilage matrix degeneration seen in the initial stages of OA, although it is difficult to draw strong conclusions from the currently available data to determine whether untreated FCDs influence the development of knee OA.
There are distinct biochemical and mechanical properties of cartilage seen in the patella compared with that of the tibia and femur. 17,30 Femoral cartilage has been shown to have a higher compressive aggregate modulus, lower permeability, lower water content, and higher proteoglycan content than patellar cartilage. 14,17,27 Two studies 2,11 in this review demonstrated elevated T2 values in patients with FCDs located on the MFC compared to patients without FCDs, while another study 31 found an apparent lack of change in global measures of volume because of significant decreases in cartilage thickness, especially of the MFC region, as well as appreciable gains in thickness in other regions. The authors of these studies 2,11 suggested that because elevated T2 values indicate increased water content and deterioration of the collagen network, 4,21 these findings may be associated with the cartilage matrix degeneration and proteoglycan loss seen in the initial stages of OA. However, Williams et al 31 included patients with baseline radiographic OA. Although findings such as these are apparent in the initial stages of OA, these results may also be explained by the distinct biochemical and mechanical properties of the cartilage within the TFJ. Therefore, the presence of FCDs may have limited influence on the development of OA.
It is important to distinguish between FCDs and knee OA. FCDs are often isolated injuries that can range from small partial-thickness lesions to large full-thickness lesions. 9,23,25 While knee OA is associated with progressive loss of articular cartilage, OA is a pathological process that differs from isolated FCDs. 5,10,15 Radiographic evidence of knee OA is characterized by the formation of osteophytes, narrowing of articular cartilage associated with sclerosis of subchondral bone, appearance of subchondral cysts, and deformity of the bone contour. 19 In contrast, FCDs may be visualized as isolated regions of the knee joint with partial- or full-thickness loss of cartilage, with normal, undamaged cartilage in the surrounding regions. Over time, an FCD may worsen in the sense that the lesion may expand in terms of the surface area and/or depth, although the expansion of these isolated injuries differs from the disease process of OA.
Of the 8 studies included in this review, the knees with FCDs showed an increased progression of cartilage damage on the MFC, 2,11,31 the PFJ, 20,28,30 the same subregion of the medial or lateral compartments, 15 and the entire knee joint in obese patients. 20 Multiple studies demonstrated that specific risk factors in combination with FCDs, such as a high BMI, 20 frequent knee bending, 29 malalignment, 15 and knee symptoms or injury, 2,11,20,28,30 can have meaningful effects on the progression of cartilage damage.
There are several limitations to this review. Most importantly, the mean follow-up time of the included studies was 64.8 months, and it may often take longer than this for knee OA to develop after an injury. 22 Only 8 studies were included (all level 3 evidence), and the high heterogeneity of the included studies and population made it difficult to draw strong conclusions from the currently available data. Additionally, older patients who have an FCD are likely to have concomitant knee OA, and ideally, this review would have included exclusively younger patients. Although 1425 knees were included in this review, not all knees were evaluated using the same outcome measures, and therefore, sample sizes were limited when comparing outcomes between studies. The inconsistency of reporting outcome measures is another limitation of the included studies. Furthermore, the overall quality of the currently available data on this topic was limited. Two studies 15,28 used data from the same multicenter study (MOST), while the authors of 3 studies 2,20,29 worked at the same research center and used data from the same multicenter OAI database. Therefore, it is likely that there is some overlap in patients, although this was not specified in these articles.
Conclusion
Patients with untreated FCDs of the knee joint are more likely to experience the progression of cartilage damage, although the studies included in this review did not demonstrate the development of radiographically evident OA within 2 years of follow-up.
Footnotes
One or more of the authors has declared the following potential conflict of interest or source of funding: R.M.F. has received educational funding from Smith & Nephew and Arthrex. E.C.M. receives royalties from Biomet and Elsevier; is a consultant for Biomet and DePuy; and receives research support from Biomet, Mitek, Smith & Nephew, and Stryker. J.T.B. is a consultant for DJ Orthopaedics, Shukla Medical, Encore Medical, and Smith & Nephew; receives royalties from Shukla Medical; receives research support from Stryker; has received hospitality payments from Encore Medical and Smith & Nephew; and has received fellowship funding from Smith & Nephew, Mitek, and Stryker. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.