Meniscal and articular cartilage changes in knee osteoarthritis: a cross-sectional double-contrast macroradiographic study

OBJECTIVE: In knee osteoarthritis (OA) damage to meniscal cartilage is associated with the changes in articular cartilage. Using double-contrast macroradiographs we determined whether the degree of meniscal cartilage damage was similar to or different from that at the corresponding regions of the articular cartilage on the tibia and femur. DESIGN: Double-contrast microfocal macroradiographs,x7-x9 magnification, were obtained of the tibio-femoral joint in 20 osteoarthritic knee patients with medial compartment disease (Kellgren and Lawrence grades I-III). The appearance of the meniscus and the femoral and tibial articular cartilage were graded separately using a 5-point scale. RESULTS: In the medial diseased compartment, articular cartilage damage on the tibia was similar to that of the meniscus, which had significantly greater (P<0.02) degenerative changes than the cartilage on the femur. In the lateral compartment, meniscal damage was significantly worse than in either tibial (P<0.04) or femoral articular cartilages (P<0.01), respectively; none was as severe as that in the medial osteoarthritic compartment. CONCLUSION: Although the cross-sectional nature of this study precluded definite aetiological inferences, this study showed that degenerative changes in the meniscal and articular cartilages were not totally variable. Because of its larger articular surface, changes in the medial femoral cartilage were less marked than at the meniscal and tibial cartilages in the osteoarthritic compartment. In the lateral compartment, meniscal damage precedes tibial and femoral articular cartilage changes. In knees with medial compartment OA, combined meniscal and articular cartilage damage would account for detection of radiographic joint space loss and not meniscal extrusion only.     

Longitudinal study of the relationship between knee angle and tibiofemoral cartilage volume in subjects with knee osteoarthritis

OBJECTIVES: There is emerging evidence that knee alignment is associated with progression of osteoarthritis (OA). The aim of this study was to examine the relationship between baseline knee angle and the rate of cartilage loss in subjects with knee OA. METHODS: One hundred and seventeen subjects with knee OA had standing radiographs and MRI on their symptomatic knee at baseline and at the 1.9+/-0.2 yr follow-up. Knee cartilage volume was measured at baseline and follow-up. Knee angle was defined as the angle subtended by a line drawn through the mid-shaft of the femur with respect to one drawn through the mid-shaft of the tibia. RESULTS: At baseline, in the medial compartment, as the angle decreased (i.e. was less varus) the tibial and femoral cartilage volume increased. In the lateral compartment, as the angle became more valgus, there was a reduction in tibial and femoral cartilage volume. In the longitudinal study, for every 1 degrees increase in baseline varus angulation there was an average annual loss of medial femoral cartilage of 17.7 micro l [95% confidence interval (CI) 6.5-28.8]. Although not statistically significant, there was a trend for a similar relationship between loss of medial tibial cartilage volume and baseline knee angle. In the lateral compartment, there was an average loss of tibial cartilage volume of 8.0 micro l (95% CI 0.0-16.0) for every 1 degrees increase in valgus angle. CONCLUSIONS: Baseline knee angle is associated with the rate of cartilage loss in the knee. Further work will be needed to determine whether therapies aimed at modifying the knee angle will reduce the progression of knee OA.     

The relationship between body composition and knee cartilage volume in healthy, middle-aged subjects

OBJECTIVE: Although obesity is widely accepted as a risk factor for knee osteoarthritis, it is not clear whether individual components of body composition, such as the mass and distribution of muscle and fat, are associated with development of the disease. This study examined the effect of measures of body composition on the longitudinal change in tibial cartilage volume. METHODS: Body composition, assessed via dual x-ray absorptiometry, and tibial cartilage volume, assessed via magnetic resonance imaging, were measured in 86 healthy men and women who were mid-life in age. Change in tibial cartilage volume was assessed by imaging each knee 2 years after the baseline measurement and determining the difference from baseline in tibial cartilage volume. Correlations were determined between the muscle and fat mass of the arm, leg, and total body and the volume of the lateral- and medial-tibial cartilage, as well as the change in tibial cartilage volume over 2 years, after adjusting for confounders. RESULTS: There was a significant association between muscle mass and the medial-tibial cartilage volume, independent of age, sex, body mass index, tibial bone area, and level of physical activity. Although there was a positive association between muscle mass and the lateral-tibial cartilage volume, this did not persist after adjustment for confounders. Loss of muscle mass was associated with an increased loss of medial- and lateral-tibial cartilage over 2 years, after adjusting for confounders. No relationship was apparent between fat mass and either medial- or lateral-tibial cartilage volume, or between fat mass and change in either medial- or lateral-tibial cartilage volume over 2 years, after adjusting for confounders. CONCLUSION: Muscle mass is an independent predictor of medial-tibial cartilage volume in healthy people in mid-life and is associated with a reduction in the rate of loss of tibial cartilage. This suggests that increased muscle mass may be protective against the onset of osteoarthritis.     

The clinical correlates of articular cartilage defects in symptomatic knee osteoarthritis: a prospective study

OBJECTIVES: To determine whether articular cartilage defects are associated with cartilage loss and joint replacement in subjects with symptomatic knee osteoarthritis (OA). METHODS: One hundred and seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of their dominant knee at baseline and 2 yr later. Cartilage defects were identified as prevalent (defect score > or =2) in each knee compartment. Occurrence of joint replacement by 4 yr was documented. RESULTS: Cartilage defects were present in 81% of medial, 64% of lateral tibiofemoral compartments and 55% of patellar cartilages. Annual patellar cartilage loss was highest in those with defects compared with no defects (5.5% vs 3.2%, P = 0.01). Tibial cartilage loss was not associated with defects in the medial (4.6% vs 5.8%, P = 0.42) or lateral (4.7% vs 6.5%, P = 0.21) tibial cartilages. Higher total cartilage defect scores (8-15) were associated with a 6.0-fold increased risk of joint replacement over 4 yr compared with those with lower scores (2-7) (95% confidence interval 1.6, 22.3), independently of potential confounders. CONCLUSIONS: Articular cartilage defects are associated with disease severity in knee OA and predict patellar cartilage loss and knee replacement.     

Phonoarthrography,musculoskeletal ultrasonography,and biochemical biomarkers for the evaluation of knee cartilage in osteoarthritis

The aim of this study was to examine the relationship among three different parameters used to assess cartilage in osteoarthritis (OA) of the knee. These parameters are phonoarthrography (Phono-A), musculoskeletal ultrasonography (MSUS) from the 4 condyles, and biochemical markers; notably, matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of proteinase (TIMP-1). A total of 100 knees with chronic idiopathic OA diagnosed according to the American College of Rheumatology (ACR) criteria were studied, together with 50 normal knees. The knee sounds were recorded by Phono-A and the cartilage thickness was measured by MSUS. All patients and controls had MMP-3 and TIMP-1 measured in a blood sample, using an enzyme-linked immunosorbent assay (ELISA). Conventional knee X-rays were obtained for diagnosis and for Kellgren–Lawrence (K-L) grading purposes. The results showed that Phono-A values were inversely correlated with cartilage thickness, both of these being sensitive parameters for cartilage degeneration. Phono-A values were higher in patients than in controls, denoting more degeneration of cartilage, and the cartilage thickness of all 4 condyles showed significant reductions in patients compared with normal controls. Most of the patients were categorized as grade 2 (36%) and grade 3 (30%) of the K-L classification. Mean levels of MMP-3 and TIMP-1 were significantly elevated in both groups but they were not correlated with each other. MMP-3 continued to rise with increasing radiological grades until grade 4, where it fell unexpectedly. In conclusion, Phono-A and cartilage thickness measured by MSUS seem to support each other. They can be used as parameters for following up cartilage in OA of the knees. The first deals with the roughness of the cartilage surface and the second with its thickness, complementing each other. MMP-3 continues to rise in early and middle grades of OA, denoting cartilage destruction.     

Longitudinal study of changes in tibial and femoral cartilage in knee osteoarthritis

OBJECTIVE: Despite the increasing interest in knee cartilage volume as an outcome measure in studies of osteoarthritis (OA), it is unclear what components of knee cartilage will be most useful as markers of structural change in the tibiofemoral joint. This study was undertaken to longitudinally compare changes in femoral and tibial cartilage volume in patients with OA. METHODS: One hundred seventeen patients with knee OA (58.1% women; mean +/- SD age 63.7 +/- 10.2 years) were examined. Femoral and tibial cartilage volumes (medial and lateral tibiofemoral joints) were determined from T1-weighted fat-saturated magnetic resonance images of the knee from coronal views. RESULTS: The study population was followed up for a mean +/- SD of 1.9 +/- 0.2 years. In the medial tibiofemoral joint, the mean +/- SD loss of cartilage was 0.15 +/- 0.30 ml/year for femoral cartilage and 0.10 +/- 0.25 ml/year for tibial cartilage. In the lateral tibiofemoral joint, the average loss was 0.15 +/- 0.22 and 0.12 +/- 0.16 ml/year for femoral and tibial cartilage, respectively. There was a significant correlation between the degree of loss of tibial cartilage and the degree of loss of femoral cartilage, in both tibiofemoral joints (r = 0.81, P < 0.001 at the medial tibiofemoral joint; r = 0.71, P < 0.001 at the lateral tibiofemoral joint). CONCLUSION: Longitudinal changes in tibial cartilage and those in femoral cartilage are strongly related to one another. This suggests that in tibiofemoral disease, measuring tibial cartilage alone may be adequate, given the facts that measurements of the total femoral cartilage are less reproducible and there are difficulties inherent in identifying the most appropriate component of femoral cartilage to measure.     

Assessing bone loss on radiographs of the knee in osteoarthritis: a cross-sectional study

OBJECTIVE: The only established system to grade subchondral bone attrition in knee osteoarthritis (OA) has low interobserver reliability. In this study, our aim was to convert this system into a reliable tool for the assessment of subchondral bone loss in knee OA. METHODS: Templates that were designed to outline the normal contours of the knee were overlaid onto conventional radiographs of a random sample of 100 knees of OA patients who were awaiting total knee replacement (TKR). Seventy-five films from individuals with chronic knee pain who were not awaiting TKR and 75 films from asymptomatic control subjects were also assessed. Bone loss was graded from 0 (no attrition) to 3 (severe attrition of >10 mm); other established radiologic features were also graded. Spearman's rho was used to determine the correlation of attrition scores with other features, and logistic regression was used to explore whether definite bone attrition was associated with night pain. RESULTS: The inter- and intraobserver reliability values were high for attrition scores and for the presence of definite attrition (score > or =2). Bone attrition was evident in 62% of films from patients awaiting TKR, in 9% of films from individuals with chronic knee pain who were not awaiting TKR, and in 1% of films from controls. In all groups, the correlation between attrition and other features was weak to moderate. There was a nonsignificant association between definite bone attrition and night pain. CONCLUSION: Bone attrition is an additional dimension of knee OA that can be measured reliably. Definite attrition may be associated with night pain.     

Tibial and femoral cartilage changes in knee osteoarthritis

BACKGROUND: Despite the increasing interest in using knee cartilage volume as an outcome measure in studies of osteoarthritis (OA), it is unclear what components of knee cartilage will be most useful as markers of structure in the tibiofemoral (TF) joint. OBJECTIVE: To compare the changes that occur in femoral and tibial cartilage volume in normal and osteoarthritic knees and how they relate to radiological grade. METHODS: 82 subjects (44 female, 38 male, age range 35-69 years) with a spectrum of radiological knee OA were examined. Each subject had femoral and tibial cartilage volume in the medial and lateral TF joint determined from T(1) weighted fat saturated magnetic resonance images of the knee. Radiological grade of OA was determined from standing knee radiographs. RESULTS: There was strong correlation between femoral and tibial cartilage volume measured in both the medial (R=0.75, p<0.001) and lateral TF joint (R=0.77, p<0.001). Similar correlations persisted when those with normal and those with OA joints were examined separately at both the medial and lateral TF joint. For each increase in radiological grade of joint space narrowing (0-3), there was a mean (SD) reduction in tibial cartilage volume of 1.00 (0.32) ml in the medial compartment and 0.53 (0.25) ml in the lateral compartment, after adjusting for differences in bone size. Similar changes were seen in the femoral cartilage. CONCLUSIONS: The amounts of tibial and femoral cartilage are strongly related. It may be that for TF joint disease, measuring tibial cartilage alone may be adequate, given that measurements of the total femoral cartilage are less reproducible and the difficulties inherent in identifying the most appropriate component of femoral cartilage to measure.     

Intra-articular hyaluranic acid compared with progressive knee exercises in osteoarthritis of the knee: a prospective randomized trial with long-term follow-up

The goal of this study was to determine whether hyaluronic acid (HA) or progressive knee exercises (PE) can improve functional parameters in patients with osteoarthritis (OA) of the knee. In a prospective clinical trial 200 knees (105 patients) with radiographic Kellgren Lawrence grade III OA were randomized and received either three intra-articular injections of hyaluronic acid (Hylan G-F 20) at one-week intervals or PE for 6 weeks. Patients were evaluated by use of the Hospital for Special Surgery (HSS) Knee Score and followed-up for 18 months. Total HSS score for HA and PE patients improved from 62.6±13.8 to 88.8±11.1 and from 65.4±12.3 to 88.3±9.1, respectively, at the end of the trial (P<0.01). There were no statistically significant differences between the groups. Twenty-one patients of the HA group were excluded from the study because they had received another form of therapy. All patients in the PE group completed the trial. The patients who dropped out had also significant improvement from 57.0±12.9 to 76.7±11.9 (P<0.01). This prospective randomized trial confirmed that both HA injections and PE result in functional improvement. HA injections also increase the levels of satisfaction of the OA patients.     

Obesity,metabolic abnormality,and knee osteoarthritis: A cross-sectional study in Korean women

Abstract

Background. This study aimed to analyze the association between knee osteoarthritis and four body size phenotypes defined by the presence or absence of metabolic abnormality and obesity.

Mehods. This was a cross-sectional study using data from 1,549 female participants of the Fifth Korean National Health and Nutrition Examination Survey. Knee osteoarthritis was defined as a Kellgren–Lawrence grade of ≥ 2. Metabolically abnormal state was defined as presence of more than one abnormality among five metabolic risk factors. Obesity was defined using body mass index. Participants were grouped into one of the four body size phenotypes: metabolically healthy normal weight (MHNW), metabolically abnormal but normal weight (MANW), metabolically healthy obesity (MHO), and metabolically abnormal obesity (MAO).

Results. The distribution of each body size phenotype was as follows: MHNW 54.7%, MANW 30.7%, MHO 4.3%, and MAO 10.3%. Prevalence of symptomatic knee osteoarthritis was higher in MANW than in MHNW, and in MAO than in MHO. In multivariable analysis, the association between symptomatic knee osteoarthritis and the body size phenotypes was as follows (OR [95% CI]): MHNW 1.00 (reference), MANW 1.54 (1.15–2.07), MHO 1.61 (0.83–3.13), and MAO 3.47 (2.35–5.14).

Conclusions. Obesity showed closest association with knee osteoarthritis when accompanied by metabolic abnormality.     

Correction to: Associations between serumIL-8 and knee symptoms,joint structures,and cartilage or bone biomarkers in patients with knee osteoarthritis

Clinical Rheumatology - There were overlaps between the article recently published in this journal [1] and the previous publications from the authors’ group [2-4] that they did not cite.]     

Glucosamine sulfate and cartilage type II collagen degradation in patients with knee osteoarthritis: randomized discontinuation trial results employing biomarkers

OBJECTIVE: To determine whether glucosamine sulfate has an effect on cartilage type II collagen degradation in patients with knee osteoarthritis (OA). METHODS: A randomized, double blind, placebo controlled glucosamine discontinuation trial was conducted in 137 subjects with knee OA, who had had at least moderate relief of knee pain after starting glucosamine. Subjects were randomized to glucosamine at prestudy dose or placebo at an equivalent dose. Treatment was continued to Week 24 or disease flare, whichever occurred first. Serum and urine samples were collected at Weeks 0, 4, 12, and 24 or flare visit. Samples were analyzed in triplicate for 2 type II collagen degradation biomarkers: C2C epitope (COL2-3/4C(long)) and C1,2C epitope (COL2-3/4C(short)). The primary outcome was the mean change in serum and urine C1,2C/C2C ratio in the glucosamine and placebo groups from baseline to final (flare or Week 24) visit. Linear regression analyses were conducted to adjust for potential confounders. Due to non-normal distributions, the data were log-transformed (lnC1,2C/C2C). Secondary outcomes included comparison of mean change scores at final visit compared to baseline for serum and urine C1,2C and C2C in the 2 treatment groups and in Flare versus No-Flare groups. RESULTS: Baseline and final visit samples were available in 130 subjects for serum analysis and 126 subjects for urinalysis. No significant difference was seen between placebo and glucosamine groups in the serum C1,2C/C2C ratio, with a mean (SD) change from baseline to final visit of 0.8 (27.8) and -0.1 (1.8), respectively (mean difference 0.9; 95% CI -6.0, 7.7, p = 0.80). Similarly, no differences between treatment groups were seen for mean change in urine C1,2C/C2C (p = 0.82), or for mean change in C2C or C1,2C. In linear regression analysis, after adjustment for sex, radiographic severity, baseline lnC1,2C/C2C ratio, WOMAC function, and flare status, treatment was not a significant predictor of final serum or urine lnC1,2C/C2C ratio. When those who experienced flare were contrasted with those without flare, there was a nonsignificant trend toward a difference in mean baseline to final visit change score for serum C1,2C/C2C ratio (p = 0.12). In addition, in the multivariable linear regression analysis, flare status showed a borderline association with final visit serum lnC1,2C/C2C ratio (p = 0.16). CONCLUSION: No statistically significant effect of glucosamine sulfate on type II collagen fragment levels in serum or urine was observed for knee OA over 6 months. Further research is necessary to elucidate which biopathologic systems, if any, are affected by glucosamine treatment. While collagen degradation products may be of value in predicting progression, at least as defined by clinical flare, a larger dataset would be needed to prove this.     

Associations between serum IL-8 and knee symptoms,joint structures,and cartilage or bone biomarkers in patients with knee osteoarthritis

Clinical Rheumatology - The aim of this study was to investigate cross-sectional associations between serum levels of IL-8 and the above outcomes in patients with knee osteoarthritis (OA). A total...     

The relationship between the knee adduction moment and knee pain in middle-aged women without radiographic osteoarthritis

OBJECTIVE:. An abnormally high knee adduction moment increases the medial tibiofemoral compartment load at the knee during gait, and is an important biomechanical marker of joint pathology. This cross-sectional study examines the relationship between the knee adduction moment and knee pain in middle-aged women without radiographic knee osteoarthritis (OA). METHODS: Three-dimensional Vicon gait analyses were performed on 20 women who had knee pain but no radiological evidence of joint pathology. RESULTS: In multivariate analysis, the peak knee adduction moment during the late stance phase of gait was inversely associated with knee pain [beta: -10.1 (95% CI -17.6, -2.7), p = 0.01] after adjustment for body mass index (BMI) and age. This explained that the knee adduction moment during late stance contributed 32% of the variance in knee pain. The peak knee adduction moment during early stance was not significantly associated with knee pain prior to and after adjustment for BMI and age. CONCLUSION: There is a significant inverse association between the peak knee adduction moment during late stance and the amount of knee pain experienced by women without radiographic evidence of joint pathology. This may represent a compensatory mechanism to reduce medial tibiofemoral joint load in the setting of knee pain.     

Radiographic osteoarthritis and pain are independent predictors of knee cartilage loss: a prospective study

Background: There is controversy about whether pain and radiographic osteoarthritis (ROA) predict subsequent cartilage loss. The aim of this study was to describe the relationship between ROA, pain and cartilage loss in the knee. Methods: We studied randomly selected subjects at baseline and approximately 2.9 years later (n= 399). The presence of ROA was assessed at baseline with a standing anteroposterior semiflexed radiograph scored using the Osteoarthritis Research Society International atlas for osteophytes (OP) and joint space narrowing (JSN). Pain was assessed by the Western Ontario McMaster Osteoarthritis Index. Subjects' medial and lateral tibial cartilage volumes were determined by magnetic resonance imaging at both time points. Results: In cross‐sectional analysis, both medial and lateral tibial cartilage volumes were lower in those with ROA. Any medial ROA predicted medial tibial cartilage loss (3.2% (standard deviation (SD) 5.6) vs 1.9% (SD 5.3) per annum) while any lateral ROA predicted both medial (4.0% (SD 6.0) vs 2.2% (SD 5.3) per annum) and lateral (3.5% (SD 5.8) vs 1.6% (SD 4.2) per annum) tibial cartilage loss (all P < 0.05). In multivariate analysis, JSN and OP at both medial and lateral sites had independent dose–response associations with tibial cartilage loss at both sites. Pain was an independent predictor of lateral, but not medial, tibial cartilage loss after taking ROA into account. Conclusions: Subjects with ROA (either JSN or OP) and, to a lesser extent, pain lose cartilage faster than subjects without ROA and the more severe the ROA the greater the rate of loss. These findings have implications for the design of clinical trials.     

Quantitative measurement of cartilage volume with automatic cartilage segmentation in knee osteoarthritis

Clinical Rheumatology - To determine the reproducibility of the automatic cartilage segmentation method using a prototype KneeCaP software (version 1.3; Siemens Healthcare, Erlangen, Germany) and...     

Biochemical/immunochemical biomarkers of osteoarthritis: utility for prediction of incident or progressive osteoarthritis

In this brief review the authors endeavored to show how methods developed for molecular studies of the development, onset, and progression of OA have been used to develop biomarker assays that might be of use in the detection of incident OA and in progression of established OA (Fig. 2). These assays involve analyses of specific molecular products in body fluids that result from the cleavage and synthesis of molecules in specific skeletal tissues and from inflammatory processes associated with OA joint disease. These assays are proving to be of value in the detection, study, and treatment of OA, especially with respect to improving understanding of the pathology of the disease and how it can best be detected and managed. Such assays also offer the potential to develop much shorter, more efficient, and cost effective clinical trials for the evaluation of potential disease-modifying therapies for OA.