Summary Objective To determine whether women experience greater knee pain severity than men at equivalent levels of radiographic knee osteoarthritis (OA). Design and methods A cross-sectional ...analysis of 2712 individuals (60% women) without knee replacement or a recent steroid injection. Sex differences in pain severity at each Kellgren–Lawrence (KL) grade were assessed by knee using visual analog scale (VAS) scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) with and without adjustment for age, analgesic use, Body mass index (BMI), clinic site, comorbid conditions, depression score, education, race, and widespread pain (WSP) using generalized estimating equations. Effect sizes (Cohen's d ) were also calculated. Analyses were repeated in those with and without patellofemoral OA (PFOA). Results Women reported higher VAS pain at all KL grades in unadjusted analyses ( d = 0.21–0.31, P < 0.0001–0.0038) and in analyses adjusted for all covariates except WSP ( d = 0.16–0.22, P < 0.0001–0.0472). Pain severity differences further decreased with adjustment for WSP ( d = 0.10–0.18) and were significant for KL grade ≤2 ( P = 0.0015) and 2 ( P = 0.0200). Presence compared with absence of WSP was associated with significantly greater knee pain at all KL grades ( d = 0.32–0.52, P < 0.0001–0.0008). In knees with PFOA, VAS pain severity sex differences were greater at each KL grade ( d = 0.45–0.62, P = 0.0006–0.0030) and remained significant for all KL grades in adjusted analyses ( d = 0.31–0.57, P = 0.0013–0.0361). Results using WOMAC were similar. Conclusions Women reported greater knee pain than men regardless of KL grade, though effect sizes were generally small. These differences increased in the presence of PFOA. The strong contribution of WSP to sex differences in knee pain suggests that central sensitivity plays a role in these differences.
Osteoarthritis (OA) and diabetes mellitus (DM) share common risk factors with a potential underlying relationship between both diseases. The purpose of this study was to investigate the longitudinal ...effects of DM on cartilage deterioration over 24-months with MR-based T2 relaxation time measurements.
From the Osteoarthritis Initiative (OAI) cohort 196 diabetics were matched in small sets for age, sex, BMI and Kellgren–Lawrence score with 196 non-diabetic controls. Knee cartilage semi-automatic segmentation was performed on 2D multi-slice multi-echo spin-echo sequences. Texture of cartilage T2 maps was obtained via grey level co-occurrence matrix analysis. Linear regression analysis was used to compare cross-sectional and changes in T2 and texture parameters between the groups.
Both study groups were similar in age (63.3 vs 63.0 years, P = 0.70), BMI (30.9 vs 31.2 kg/m2, P = 0.52), sex (female 53.6% vs 54.1%, P = 0.92) and KL score distribution (P = 0.97). In diabetics, except for the patella, all compartments showed a significantly higher increase in mean T2 values when compared to non-diabetic controls. Global T2 values increased almost twice as much; 1.77ms vs 0.98ms (0.79ms CI: 0.39,1.19) (P < 0.001). Additionally, global T2 values showed a significantly higher increase in the bone layer (P = 0.006), and in a separate analysis of the texture parameters, diabetics also showed consistently higher texture values (P < 0.05), indicating a more disordered cartilage composition.
Cartilage T2 values in diabetics show a faster increase with a consistently more heterogeneous cartilage texture composition. DM seems to be a risk factor for developing early OA with an accelerated degeneration of the articular cartilage in the knee.
To determine the relationship of meniscal damage to magnetic resonance imaging (MRI) features of compartment-specific patellofemoral joint (PFJ) osteoarthritis (OA) at baseline and 2 years later.
...Individuals from a prospective cohort of individuals aged 50–79 with or at risk of knee OA were included. At the 60-month and 84-month study visit, Whole-Organ MRI Score (WORMS) was used to assess meniscal tears and extrusions as well as cartilage damage and bone marrow lesions (BMLs) in the medial and lateral patella and trochlea. Worsening of structural features was defined as any increase in WORMS score from 60 to 84 months. Logistic regression was used to determine the cross-sectional and longitudinal relation of meniscus damage to features of compartment-specific PFJ OA.
Relative to knees without lateral meniscal pathology at baseline, those with grades 3–4 lateral meniscal tear and extrusion had greater risk of worsening of cartilage damage in the lateral PFJ 2 years later (Risk ratio: 1.7 95% CI: 1.1–2.7) and (1.7 1.2–2.5), respectively. Relative to those without medial meniscal pathology at baseline, those with grades 1–2 (0.6 0.4–0.9) and 3–4 (0.7 0.5–1.0) medial meniscal tears had lower risk of worsening of BMLs in the medial PFJ 2 years later.
Meniscal tear and extrusion are associated with increased risk of medial and lateral PFJ OA and more severe meniscal pathology is associated with worsening of PFJ OA 2 years later. Lateral meniscal pathology appears to be more detrimental to the lateral PFJ.
Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Saturated and n-6 fatty acids (FAs) increase, whereas n-3 FAs reduce inflammation. We examined whether FA levels ...affected the development of OA.
We studied participants from the Multicenter Osteoarthritis study (MOST) at risk of developing knee OA. After baseline, repeated knee x-rays and MRIs were obtained and knee symptoms queried through 60 month follow-up. Using baseline fasting samples, serum FAs were analyzed with standard assays. After excluding participants with baseline OA, we defined two sets of cases: those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage loss and synovitis and of knee pain using WOMAC and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of saturated, n-3 and n-6 FAs adjusting for age, sex, BMI, education, race, baseline pain and depressive symptoms.
We studied 260 cases with incident symptomatic and 259 with incident radiographic OA. Mean age was 61 years (61% women). We found no signficant nor suggestive associations of FA levels with incident OA (e.g., for incident symptomatic OA, OR per s.d. increase in n-3 FA 1.00 (0.85, 1.18) nor with any OA outcome in knee or hand.
Despite previously described effects on systemic inflammation, blood levels of FAs were not associated with risk of later knee OA or other OA outcomes.
Summary Background Vitamin K-dependent (VKD) proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies ...suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence. Objective To clarify what joint tissues vitamin K is relevant to in OA, we investigated the cross-sectional and longitudinal association between vitamin K status and knee OA structural features measured using magnetic resonance imaging (MRI). Methods Plasma phylloquinone (PK, vitamin K1) and dephosphorylated-uncarboxylated MGP ((dp)ucMGP) were measured in 791 older community-dwelling adults who had bilateral knee MRIs (mean ± SD age = 74 ± 3 y; 67% female). The adjusted odds ratios (and 95% confidence intervals) OR (95%CI) for presence and progression of knee OA features according to vitamin K status were calculated using marginal models with generalized estimating equations (GEEs), adjusted for age, sex, body mass index (BMI), triglycerides and other pertinent confounders. Results Longitudinally, participants with very low plasma PK (<0.2 nM) were more likely to have articular cartilage and meniscus damage progression after 3 years OR (95% CIs): 1.7(1.0–3.0), 2.6(1.3–5.2) respectively compared to sufficient PK (≥1.0 nM). Higher plasma (dp)ucMGP (reflective of lower vitamin K status) was associated with higher odds of meniscus damage, osteophytes, bone marrow lesions, and subarticular cysts cross-sectionally ORs (95% CIs) comparing highest to lowest quartile: 1.6(1.1–2.3); 1.7(1.1–2.5); 1.9(1.3–2.8); 1.5(1.0–2.1), respectively. Conclusion Community-dwelling men and women with very low plasma PK were more likely to have progression of articular cartilage and meniscus damage. Plasma (dp)ucMGP was associated with presence of knee OA features but not progression. Future studies are needed to clarify mechanisms underlying vitamin Ks role in OA.
The purpose of this study was to assess the associations between serum/urine biomarkers for osteoarthritis and magnetic resonance (MR) imaging measures of cartilage composition and joint structure ...(cartilage, meniscus, and bone marrow), using MR imaging data from the Osteoarthritis Initiative (OAI).
141 subjects with Kellgren Lawrence (KL) grades 0–3 in the right knee and with available serum/urine biomarker assays were selected from the OAI. Cartilage magnetic resonance imaging (MRI) T2 measurements were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. Compartment-specific knee morphologic grading whole-organ magnetic resonance imaging score (WORMS) in the cartilage, meniscus, and bone marrow was also performed. We focused on associations of serum hyaluronan (sHA), serum cartilage oligomeric matrix protein (sCOMP), serum matrix metalloproteinase-3 (sMMP3), and Urine Carboxy-Terminal Telepeptides of Type II Collagen (uCtX-II)) with MRI parameters (T2, WORMS), assessed using partial correlations adjusted for age, gender, body mass index (BMI), KL grade in both knees, and diabetes status.
Higher levels of sHA, sMMP3 and sCOMP were correlated (P < 0.05) with T2 of the lateral femur (r = 0.18 to 0.32) and lateral tibia (r = 0.17 to 0.23), and with average T2 of all knee regions (r = 0.23). uCTXII was correlated with patellar T2 (r = 0.19, P = 0.04). Among the morphologic measures, sHA and sMMP3 was positively correlated (r = 0.17 to 0.21, P < 0.05) with meniscal damage.
This study suggests weak, but statistically significant, correlations between serum biomarkers of OA (sHA, sCOMP, and sMMP3) and MRI T2 measures of cartilage extra-cellular matrix degeneration.
Summary Objective To determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years. Methods The Multicenter Osteoarthritis Study (MOST) is a longitudinal ...study of 50–79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants. Results Analyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI} = 1.01 {0.78–1.32}, P = 0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI} = 1.28 {1.08–1.52}, P = 0.0052). Conclusion Quadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men.
To investigate change in knee cartilage composition over 96 months in overweight and obese participants with constant weight compared to those with weight loss (WL), and to assess how different WL ...regimens are associated with these changes.
We studied right knees of 760 participants (age 62.6 ± 9.0y; 465 females) with a baseline body mass index (BMI) >25 kg/m2 from the Osteoarthritis Initiative with mild to moderate or with risk factors for knee osteoarthritis. Participants losing weight (>5% of baseline BMI over 72 months; N = 380) were compared to controls with stable weight (SW, N = 380). Participants losing weight were categorized based on WL method (diet and exercise, diet only, exercise only) and compared to those with stable weight. Magnetic resonance imaging (MRI) at 3T was performed at baseline, 48- and 96-months. The association of WL and WL method with change in cartilage composition, measured with T2 mapping, was analyzed using mixed random effects models.
Compared to SW, WL was associated with a significantly slower increase in global (averaged over all compartments) cartilage T2 (adjusted mean difference of change in T2 ms/year 95% CI between the groups: 0.24 0.20, 0.41 ms/year; P < 0.001) and global deep layer cartilage T2 0.35 0.20, 0.42 ms/year; P < 0.001), suggesting slower cartilage deterioration. Compared to the SW group, slower increases in global T2 were observed in the diet and diet and exercise groups, but not in the exercise only group (P = 0.042, P = 0.003 and P = 0.85, respectively).
Our results suggest that WL may slow knee cartilage degeneration over 96 months, and that these potential benefits may differ by method of WL.
Summary Objectives To provide a comprehensive simultaneous relation of various semiquantitative knee OA MRI features as well as the presence of baseline radiographic osteoarthritis (OA) to ...quantitative longitudinal cartilage loss. Methods We studied Multicenter OA Study (MOST) participants from a longitudinal observational study that included quantitative MRI measurement of cartilage thickness. These subjects also had Whole Organ MRI Score (WORMS) scoring of cartilage damage, bone marrow lesions (BMLs), meniscal pathology, and synovitis, as well as baseline radiographic evaluation for Kellgren and Lawrence (KL) grading. Knee compartments were classified as progressors when exceeding thresholds of measurement variability in normal knees. All potential risk factors of cartilage loss were dichotomized into “present” (score ≥2 for cartilage, ≥1 for others) or “absent”. Differences in baseline scores of ipsi-compartmental risk factors were compared between progressor and non-progressor knees by multivariable logistic regression, adjusting for age, sex, body mass index, alignment axis (degrees) and baseline KL grade. Odds ratios (OR) and 95% CIs were calculated for medial femorotibial compartment (MFTC) and lateral femorotibial compartment (LFTC) cartilage loss. Cartilage loss across both compartments was studied using Generalized Estimating Equations. Results 196 knees of 196 participants were included (age 59.8 ± 6.3 years mean ± SD, BMI 29.5 ± 4.6, 62% women). For combined analyses of MFTC and LFTC, baseline factors related to cartilage loss were radiographic OA (KL grade ≥2: aOR 4.8 2.4–9.5, cartilage damage (aOR 2.3 1.2–4.4)), meniscal damage (aOR 3.9 2.1–7.4) and extrusion (aOR 2.9 1.6–5.3), all in the ipsilateral compartment, but not BMLs or synovitis. Conclusion Baseline radiographic OA and semiquantitatively (SQ) assessed MRI-detected cartilage damage, meniscal damage and extrusion, but not BMLs or synovitis is related to quantitatively measured ipsi-compartmental cartilage thinning over 30 months.
BACKGROUND:Patients with knee osteoarthritis may undergo total knee replacement too early or may delay or underuse this procedure. We quantified these categories of total knee replacement utilization ...in 2 cohorts of participants with knee osteoarthritis and investigated factors associated with each category.
METHODS:Data were pooled from 2 multicenter cohort studies that collected demographic, patient-reported, radiographic, clinical examination, and total knee replacement utilization information longitudinally on 8,002 participants who had or were at risk for knee osteoarthritis and were followed for up to 8 years. Validated total knee replacement appropriateness criteria were longitudinally applied to classify participants as either potentially appropriate or likely inappropriate for total knee replacement. Participants were further classified on the basis of total knee replacement utilization into 3 categoriestimely (indicating that the patient had total knee replacement within 2 years after the procedure had become potentially appropriate), potentially appropriate but knee not replaced (indicating that the knee had remained unreplaced for >2 years after the procedure had become potentially appropriate), and premature (indicating that the procedure was likely inappropriate but had been performed). Utilization rates were calculated, and factors associated with each category were identified.
RESULTS:Among 8,002 participants, 3,417 knees fulfilled our inclusion and exclusion criteria and were classified into 1 of 3 utilization categories as follows290 knees (8% of the total and 9% of the knees for which replacement was potentially appropriate) were classified as “timely”, 2,833 knees (83% of the total and 91% of those for which replacement was potentially appropriate) were classified as “potentially appropriate but not replaced”, and 294 knees (comprising 9% of the total and 26% of the 1,114 total knee replacements performed) were considered to be “likely inappropriate” yet underwent total knee replacement and were classified as “premature”. Of the knees that were potentially appropriate but were not replaced, 1,204 (42.5%) had severe symptoms. Compared with the patients who underwent timely total knee replacement, the likelihood of being classified as potentially appropriate but not undergoing total knee replacement was greater for black participants and the likelihood of having premature total knee replacement was lower among participants with a body mass index of >25 kg/m and those with depression.
CONCLUSIONS:In 2 multicenter cohorts of patients with knee osteoarthritis, we observed substantial numbers of patients who had premature total knee replacement as well as of patients for whom total knee replacement was potentially appropriate but had not been performed >2 years after it had become potentially appropriate. Further understanding of these observations is needed, especially among the latter group.
CLINICAL RELEVANCE:Undergoing total knee replacement too early may result in little or no benefit while exposing the patient to the risks of a major operation, whereas waiting too long may cause limitations in physical activity that in turn increase the risk of additional disability and chronic disease; however, little is known about timing of this surgery. We quantified the extent of premature, timely, and delayed use, and found a high prevalence of both premature and delayed use.
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