Structural Progression Of Knee Osteoarthritis Research Articles

Walking, running, and recreational sports for knee osteoarthritis: An overview of the evidence.

We provided an overview of narrative reviews, systematic reviews, and meta-analyses that summarize primary evidence of how physical activity (PA) relates to structural progression of knee osteoarthritis (OA). This overview can serve as a resource for healthcare providers when recommending PA to patients with, or at risk, for knee OA. We searched the PubMED database for publications on "exercise" [MeSH Terms] and "knee osteoarthritis" [MeSH Terms]. We restricted our search to review articles, originally published in English, from 2005 to 2020. We then added several original studies to provide more detailed support of the findings of the review articles, based on the authors familiarity with the literature. We summarized the findings of 20 reviews and an additional 12 original studies. We found consistent evidence that common forms of PA (walking, running, and certain recreational sports) are not related to structural progression of knee OA, and can be safely recommended to patients with, or at risk, for knee OA. Healthcare providers can refer to this overview of the evidence, as well as current PA guidelines, when recommending PA to their patients with, or at risk for, knee OA. Future studies can support PA guidelines that target preserving the structural integrity of the knees.

Meniscus position and size in knees with versus without structural knee osteoarthritis progression: data from the osteoarthritis initiative

ObjectiveTo explore whether and which quantitative 3D measures of medial and/or lateral meniscus position and size are associated with subsequent medial femorotibial structural progression of knee osteoarthritis and to determine the correlation between central slice and total meniscus measures.Materials and MethodsKnees with radiographic osteoarthritis from Osteoarthritis Initiative participants with longitudinal medial MRI-based cartilage thickness and radiographic joint space width (JSW) loss over 12 months were selected. These 37 structural progressor knees (64.7 ± 8.0y, 30.2 ± 4.6 kg/m2, 35% men) were matched 1:1 to 37 non-progressor knees (64.6 ± 9.8y, 30.2 ± 4.4 kg/m2, 35% men) without cartilage thickness or JSW loss. Quantitative measures of meniscus position and size were computed from manual segmentations of coronal baseline MRIs. Cohen’s D was used as measure of effect size.ResultsMaximum extrusion distance of the total medial meniscus and mean extrusion in the central 5 and in the central slice were greater for progressor than non-progressor knees (Cohen’s D 0.58–0.66). No significant differences were observed for medial tibial coverage or mean extrusion (entire meniscus). Among medial meniscus morphology measures, only mean height differed between progressor vs non-progressor knees (Cohen’s D 0.40). Among lateral meniscus measures, height and volume were greater in progressor vs. non-progressor knees (Cohen’s D 0.46–0.83). Mean extrusion measures were highly correlated between the entire meniscus and the central (r = 0.88) or the central 5 (r = 0.93) slices.Conclusions3D maximum and central medial meniscus extrusion may serve as predictors for subsequent structural progression. Central meniscus extrusion measures could substitute 3D extrusion measurement across the entire meniscus.

The association between vitamin K and medial tibial-femoral knee osteoarthritis progression: Data from the osteoarthritis initiative

ObjectiveWe sought to examine the prospective association of vitamin K with radiographic progression of knee osteoarthritis. MethodsIn OAI, 1977 participants with radiographic knee OA and having dietary data at baseline were followed up to 12, 24, 36 and 48 months. Vitamin K was assessed with a Block Brief Food Frequency Questionnaire completed at baseline. To evaluate knee OA progression, we used quantitative medial tibiofemoral joint space width (JSW) based on plain radiographs. Progression was defined by measured Joints Space Width (JSW). The generalized linear mixed model was used to test the association of vitamin K and change in JSW over time, while adjusting for baseline KL grade and other potential confounding factors. ResultsWe found a relationship between dietary Vitamin K with structural progression of knee osteoarthritis measured by quantitative JSW in a dose response manner. When stratified among KL groups, a significant trend was seen in the KL2 (p ​< ​0.025) ConclusionOur results suggest that decreased vitamin K intake from food may be associated with increased progression of knee OA. Replication of these findings in other studies validating decreased vitamin K intake leading to increased knee OA progression are needed. SignificanceThis study provides insight into a potential novel risk factor for the progression of knee OA. These findings have may have clinical implications given the potential for Vitamin K to be a simple therapy for knee OA.

Effect of atorvastatin on knee structure and pain in patients with knee osteoarthritis: a randomised controlled trial

Purpose: Observational studies have shown an effect of oral statin on reducing structural progression of knee osteoarthritis. However, no randomised controlled trials have been performed. This study examined the effect of atorvastatin compared to placebo on reducing structural progression and improving symptoms in participants with symptomatic knee osteoarthritis. Methods: A multicentre, randomised, parallel-group, double-blind, placebo-controlled trial was conducted in Melbourne, Hobart, and Adelaide, Australia. Participants aged 40-70 years with symptomatic knee osteoarthritis assessed by the American College of Rheumatology criteria were randomly assigned in a 1:1 ratio to receive oral atorvastatin 40 mg (n=151) or inactive matching placebo (n=153) once daily over two years. The primary outcome was annual percentage change in tibial cartilage volume assessed using magnetic resonance imaging (MRI) over two years. Secondary outcomes were worsening of tibiofemoral cartilage defects and bone marrow lesions (BMLs) assessed using MRI and change in knee pain and function assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) over two years. Intention-to-treat analyses were performed. Analysis of intervention effects according to the absence or presence of BMLs at baseline was pre-specified. Results: Of 304 participants (mean age 55.7 years, 55.6% female), 248 (81.6%) completed the trial. Annual change in tibial cartilage volume was not significantly different between groups [atorvastatin: -0.26% (95% CI -0.92% to 0.41%) vs. placebo: -0.91% (95% CI -1.52% to -0.30%), p=0.15]. No significant between-group differences were observed in worsening of cartilage defects (atorvastatin: 59.6% vs. placebo: 63.4%, p=0.56) or BMLs (57.6% vs. 57.5%, p=0.99), or change in WOMAC pain (-35.9 vs. -31.6, p=0.78) or function score (-90.7 vs. -92.8, p=0.97). In those without BMLs at baseline (n=105), annual change in tibial cartilage volume was significantly different between the atorvastatin and placebo groups [0.50% (95% CI -0.88% to 1.87%) vs. -1.19% (95% CI -2.09% to -0.30%)] where significant cartilage volume loss was observed in the placebo group but not in the atorvastatin group with a between-group difference of -1.69% (95% CI -3.36% to -0.02%, p=0.047) (Table 1). There were no significant differences in adverse events between groups. Conclusions: Among participants with symptomatic knee osteoarthritis, oral atorvastatin 40 mg once daily did not reduce knee cartilage loss or knee pain over two years. However, atorvastatin reduced cartilage loss in those without BMLs, suggesting atorvastatin may have a disease-modifying effect in those with knee osteoarthritis and without BMLs.Table 1Change in cartilage volume, cartilage defects, bone marrow lesions, knee pain and functionWithin-group change, mean (95% CI)Between-group difference Atorvastatin - PlaceboP for interaction between BMLs and treatmentAtorvastatin (n=151)Placebo (n=153)Mean difference (95% CI)PAnnual % change in tibial cartilage volume-0.26 (-0.92 to 0.41)-0.91 (-1.52 to -0.30)0.66 (-0.24 to 1.55)0.15Without BMLs0.50 (-0.88, 1.87)-1.19 (-2.09, -0.30)-1.69 (-3.36, -0.02)0.0470.11With BMLs-0.61 (-1.37, 0.16)-0.75 (-1.54, 0.04)-0.14 (-1.19, 0.91)0.79Change in WOMAC pain (0-500)-35.9 (-60.1 to -11.7)-31.6 (-49.2 to -14.0)-4.3 (-34.9 to 26.4)0.78Without BMLs-36.0 (-84.1, 12.2)-26.9 (-59.0, 5.1)-9.0 (-69.4, 51.4)0.760.83With BMLs-35.9 (-62.6, -9.1)-34.4 (-56.2, -12.6)-1.4 (-36.4, 33.5)0.94Change in WOMAC function (0-1700)-90.7 (-169.5 to -11.9)-92.8 (-152.3 to -33.4)2.1 (-99.7 to 103.9)0.97Without BMLs-80.3 (-234.5, 73.8)-58.8 (-168.7, 51.1)-21.5 (-226.1, 183.0)0.830.74With BMLs-95.6 (-182.9, -8.2)-113.0 (-185.4, -40.7)17.4 (-97.5, 132.4)0.77No (%)No (%)Odds ratio (95% CI)Atorvastatin vs. PlaceboPP for interaction between BMLs and treatmentWorsening of cartilage defects90 (59.6)97 (63.4)0.86 (0.51, 1.44)0.56Without BMLs25 (52.1)34 (59.6)0.72 (0.30, 1.69)0.440.64With BMLs65 (63.1)63 (65.6)0.92 (0.49, 1.72)0.79Worsening of BMLs87 (57.6)88 (57.5)1.00 (0.62, 1.63)0.99Without BMLs18 (37.5)30 (52.6)0.50 (0.20, 1.29)0.150.09With BMLs70 (68.0)58 (60.4)1.38 (0.74, 2.55)0.31 Open table in a new tab

Quantitative measures of the medial meniscus are associated with progression of knee osteoarthritis - data from the fnih biomarker study

Purpose: Menisci are important fibrocartilage structures that protect the articular cartilage during joint mobility and help distributing mechanical load in the joint. Meniscal tears and extrusion, as scored semi-quantitatively by expert radiologists, have been shown to predict and be associated with clinical and structural progression of knee osteoarthritis (KOA). More recently, MRI-based quantitative measurement technology has been developed to determine the 3D position and size of the menisci, including tibial coverage by the meniscus.

Association of walking cadence with knee adduction angular impulse while controlling for speed in patients with knee osteoarthritis

Purpose: Walking cadence and speed are correlated and may affect knee loading in different ways. Previous research suggests higher walking cadence at baseline is associated with less structural progression of knee osteoarthritis (OA), presumably due to lower cumulative knee loading. The knee adduction angular impulse during walking is a surrogate measure of medial compartment load throughout stance and is associated with greater knee OA progression and knee pain. Thus, we aimed to test the hypothesis that higher walking cadence is associated with lower knee adduction angular impulse, while controlling for walking speed, in patients with medial knee OA. Methods: We analyzed existing data from 691 patients with medial compartment knee OA and varus alignment who participated in studies investigating rehabilitative and surgical interventions. The mean age and body mass index were 47±9 years and 30±5 kg/m2, respectively. All patients had undergone a baseline 3D quantitative gait analysis at preferred walking speed and cadence. Analyses included spatiotemporal characteristics and external knee joint moments. We used multivariate linear regression to test the association of cadence with knee adduction angular impulse while controlling for walking speed. We repeated the regression analyses while sequentially replacing the dependent variable knee adduction angular impulse with the first peak knee adduction moment, second peak knee adduction moment, peak knee flexion moment and peak vertical ground reaction force. We also repeated these analyses separately for females (n=163) and males (n=528). Lastly, we split the cohort into higher (n=462) and lower (n=229) cadence groups based on a cut-point of 100 steps/min - the minimum recommended walking cadence for adults - and plotted their adjusted means using analysis of covariance controlling for walking speed. Results: Mean ± SD for cadence, speed and knee adduction angular impulse were 1.10±0.19 m/s, 103±10 steps/min, 1.59±0.56 %BW.Ht.s; respectively. While controlling for walking speed, cadence was negatively associated with knee adduction angular impulse (unstandardized B [95% CI], p-value = -0.020 [-0.027 to -0.015], p<0.001), suggesting every 1 step/min increase in cadence was associated with a 0.02 %BW.Ht.s decrease in knee adduction angular impulse. For example, an increase in cadence of 20 steps/min (e.g. from 100 to 120 steps/min) was associated with a decrease in knee adduction angular impulse of 0.4 %BW.Ht.s (e.g. from 1.6 to 1.2 %BW.Ht.s), and when described in terms of the percent changes from the present sample means, this translated to a 20% increase in cadence associated with a 25% decrease in knee adduction angular impulse. The association was slightly higher in females (-0.028 [-0.039 to -0.016], p<0.001) than males (-0.017 [-0.024 to -0.009], p<0.001). While controlling for walking speed, cadence was also negatively associated with other surrogate measures of knee loading (Table 1). Adjusted means for higher and lower cadence groups are shown in Figure 1, illustrating that patients with medial knee OA walking with higher cadence (109±6 steps/min) have lower knee adduction angular impulse than patients walking at the same speed but with lower cadence 92±7 steps/min) (adjusted knee adduction angular impulse mean difference [95% confidence interval]: -0.27 %BW.Ht.s [-0.37 to -0.16]). Conclusions: In patients with medial knee OA, when controlling for walking speed, higher walking cadence is associated with lower knee adduction angular impulse. Although lower in size, the negative association of cadence remained with other surrogate measures of knee loading while controlling for walking speed. Future prospective studies should investigate the hypothesis that gait retraining to increase cadence at a given walking speed has beneficial biomechanical and clinical effects in patients with knee OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Meniscus position and size in knees with versus without structural knee osteoarthritis progression - data from the osteoarthritis initiative

To explore whether and which quantitative 3D measures of medial and/or lateral meniscus position and size are associated with subsequent medial femorotibial structural progression of knee osteoarthritis and to determine the correlation between central slice and total meniscus measures. Knees with radiographic osteoarthritis from Osteoarthritis Initiative participants with longitudinal medial MRI-based cartilage thickness and radiographic joint space width (JSW) loss over 12 months were selected. These 37 structural progressor knees (64.7 ± 8.0y, 30.2 ± 4.6 kg/m2, 35% men) were matched 1:1 to 37 non-progressor knees (64.6 ± 9.8y, 30.2 ± 4.4 kg/m2, 35% men) without cartilage thickness or JSW loss. Quantitative measures of meniscus position and size were computed from manual segmentations of coronal baseline MRIs. Cohen’s D was used as measure of effect size. Maximum extrusion distance of the total medial meniscus and mean extrusion in the central 5 and in the central slice were greater for progressor than non-progressor knees (Cohen’s D 0.58–0.66). No significant differences were observed for medial tibial coverage or mean extrusion (entire meniscus). Among medial meniscus morphology measures, only mean height differed between progressor vs non-progressor knees (Cohen’s D 0.40). Among lateral meniscus measures, height and volume were greater in progressor vs. non-progressor knees (Cohen’s D 0.46–0.83). Mean extrusion measures were highly correlated between the entire meniscus and the central (r = 0.88) or the central 5 (r = 0.93) slices. 3D maximum and central medial meniscus extrusion may serve as predictors for subsequent structural progression. Central meniscus extrusion measures could substitute 3D extrusion measurement across the entire meniscus.

Biomechanical factors related to clinical vs. structural progression of knee OA

Purpose: The purpose of this presentation is to provide an overview of the in vivo human gait studies investigating biomechanical factors related to clinical (i.e. evidence of structural damage and symptoms) versus structural severity/progression in knee osteoarthritis (OA). Background: Biochemical responses, commonly triggered by biomechanical factors, are related to changes in the homeostatic balance of articular cartilage synthesis and degradation associated with OA. Historically, cartilage degradation has been the hallmark for OA; however, its effects on other structures such as muscles, ligaments, synovium and nerves are gaining recognition. The presence of symptoms is also fundamental in diagnosing OA (e.g. pain, stiffness, swelling, etc.), with pain as the most common symptom for seeking clinical care. Importantly, the level of pain and degree of structural damage are not well correlated in individuals with knee OA and suggest that each component may progress using different pathways. Much of our existing knowledge about OA mechanisms comes from fundamental in vitro or animal model studies that link biomechanical loading to biochemical responses related to OA processes (i.e. cartilage damage, inflammation and pain). In human models, gait (i.e. walking) studies have been the primary source of information for understanding knee joint-level loading in knee OA, and much of the work to date has examined joint moments from biomechanical models. Over the past 10 years an increasing number of studies have examined muscle activation patterns, including the contribution of muscles when modelling joint contact loads associated with OA processes. Summary: Differences in joint moment and muscle activation patterns have been associated with the level of structural severity, and evidence exists that associates specific pattern features with increased risk of structural progression defined using radiography and magnetic resonance imaging. Although fewer studies have focused on biomechanical and muscle activation patterns associated with clinical severity and risk of clinical progression, interesting trends are emerging and differ from features observed for structural outcomes. These gait studies provide information related to the magnitude, distribution, pattern and duration of joint loading. Features associated with the magnitude of joint moments are related to structural processes, whereas muscle function features and patterns of loading are linked with clinical outcomes such as joint replacement surgery. A critical evidence gap exists among these human studies related to the effect of loading frequency on OA progression. Aerobic exercise, particularly increasing walking frequency, is recommended across international non-surgical, non-pharmacological knee OA management guidelines based on pain relief, improved general health (i.e. cardiovascular outcomes), and the response of healthy cartilage to physical activity and exercise, but less on the effects on damaged tissue. The few human studies that link joint loading features during locomotion to biomarkers related to cartilage damage and pain processes in individuals with knee OA provide early evidence of a causal effect. Conclusions: Collectively, the work to date suggests that different biomechanical targets exist for structural versus clinical OA processes and should be considered when tailoring person-specific interventions.

Long-term effects of vitamin d supplementation and maintaining vitamin d sufficiency on knee osteoarthritis over 5 years

Purpose: Epidemiological studies suggest that vitamin D deficiency is associated with knee symptom and structural progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) failed to demonstrate a significant effect of vitamin D supplementation on OA, probably due to selecting OA participants with and without vitamin D deficiency, short duration of the studies and a large proportion of participants in the placebo group reaching vitamin D sufficiency (61.3% of patients in the placebo group achieved a serum 25-hydroxyvitamin D [25(OH)D] level of > 60 nmol/l at 3 months of a clinical trial). We conducted the Vitamin D Effect on Osteoarthritis (VIDEO) clinical trial by selecting knee OA participants with vitamin D insufficiency and reported that there was no significant effect of vitamin D supplementation over 2 years on cartilage volume loss and knee pain assessed using the WOMAC scale. However, there was a significant reduction in knee pain evaluated by VAS knee pain scale, an improvement in physical function and a decrease in joint effusion-synovitis volume and bone marrow oedema compared to the placebo group. We aimed to describe the effect of vitamin D supplementation for 2 years on knee symptoms compared to placebo after 3 years of cessation of treatment, and to examine whether those maintaining sufficient serum vitamin D levels over 5 years had reduced knee symptoms compared with those who did not maintain adequate vitamin D levels over 5 years in patients with knee OA. Methods: Participants with symptomatic knee OA and low 25(OH)D (12.5-60 nmol/l) were enrolled in the VIDEO clinical trial. Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years. 172 participants who enrolled in the study from Hobart were followed up after 3 years (5 years from baseline) of the cessation of the treatment to assess knee symptoms and vitamin D levels. Participants with serum 25(OH)D measurements at month 0, 3, 24 and 60 and were included in the post-hoc analyses. The incidence of total knee replacement was recorded and they were excluded from the symptom analyses. Participants were classified as maintaining sufficient vitamin D group if they maintained serum 25(OH)D >50 nmol/l at month 3, 24 and 60 (n = 79), and not maintaining sufficient vitamin D group (25[OH]D ≤50 nmol/l at month 3, 24 and 60, n = 62). Knee symptoms were assessed at baseline, 3, 6, 12, 24 and 60 months using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results: The level of 25(OH)D dropped in the vitamin D group (from 87.0 nmol/l to 53.3 nmol/l) over 3 years after the cessation of the treatment. Placebo group slightly increased the vitamin D level (53.3 nmol/l to 61.7 nmol/l) over 3 years. Knee pain increased from the end of the study (2nd year) to 5 years of follow-up in the treatment (81.8 to 91.7) and placebo (75.8 to 101.1) groups. 16.7% of the participants in vitamin D and 18.5% of the participants in placebo group underwent total knee replacement surgery. There were no significant differences in WOMAC pain, stiffness or dysfunction scores and total knee replacement surgery rates or change in symptom between Vitamin D and placebo groups after 3 years of cessation of the supplementation. However, participants who maintained adequate vitamin D levels over 5 years had significantly less WOMAC knee pain (β: −38.4, 95% CI: −69.2, −7.7) and physical dysfunction (β: −98.5, 95% CI: −193.8, −3.1) than participants with vitamin D deficiency over 5 years in multivariable analyses after adjusting for age, sex and BMI.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusions: Vitamin D supplementation over 2 years did not result in significant differences in change in knee symptom score over 5 years compared to placebo. However, knee OA patients maintaining sufficient serum vitamin D levels over long-term had more improvement in knee pain and physical function than those who did not maintain adequate vitamin D levels, suggesting a beneficial effect of maintaining sufficient serum vitamin D for knee OA.

Dynamic and static knee alignment at baseline predict structural abnormalities on MRI associated with medial compartment knee osteoarthritis after 2 years

BackgroundDynamic and static varus alignment, both, have been reported as risk factors associated with structural progression of knee osteoarthritis. However the association of none of the static and dynamic alignment with structural, clinical, and functional progression associated with knee osteoarthritis has not been assessed yet in a longitudinal study. MethodsForty-seven women with early and established medial knee osteoarthritis were evaluated. Static and dynamic alignment as well as MRI detected structural features, clinical, and functional characteristics of patients were assessed at baseline and at 2 years follow-up. Associations between baseline static and dynamic alignment with structural, functional, and clinical characteristics at the time of entry, as well as the changes over 2 years were evaluated. FindingsBoth static and dynamic varus alignment at baseline were significantly associated with osteoarthritis related tibio-femoral joint structural abnormalities detected on MRI, at the time of entry. Only the magnitude of varus thrust at baseline was predictive of the changes in the presence of meniscal maceration over two years. None of the static or dynamic measures of knee joint alignment were associated with clinical characteristics associated with medial knee osteoarthritis. InterpretationThe key finding of this study is that both frontal plane dynamic and static alignment, are associated with structural abnormalities in patients with medial knee osteoarthritis.

Development of a clinical prediction algorithm for knee osteoarthritis structural progression in a cohort study: value of adding measurement of subchondral bone density

BackgroundRisk prediction algorithms increase understanding of which patients are at greatest risk of a harmful outcome. Our goal was to create a clinically useful prediction algorithm for structural progression of knee osteoarthritis (OA), using medial joint space loss as a proxy; and to quantify the benefit of including periarticular bone mineral density (BMD) in the algorithm.MethodsParticipants were from the Osteoarthritis Initiative (OAI) Progression Cohort, with X-ray readings of medial joint space at 36- and 48-month visits, and a 30- or 36-month medial-to-lateral tibial BMD ratio (M:L BMD ratio) value. Loss of medial joint space was the outcome and clinically available factors associated with OA progression were employed in the base prediction algorithm, with M:L BMD ratio added to an enhanced prediction algorithm. The benefit of adding M:L BMD ratio was evaluated by change in area under the ROC curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).ResultsFive hundred thirty-three participants were included; 51 (14%) had medial joint space loss; 47% were female; the mean (SD) age was 64.6 (9.2) years and BMI was 29.6 (4.8) kg/m2. The base algorithm model included age, BMI, gender, recent injury, knee pain, and hand OA as predictors and had an AUC value of 0.65. The algorithm adding M:L BMD ratio had an AUC value of 0.73, and the AUC, NRI and IDI were all significantly improved (p ≤ 0.002).ConclusionsThis clinical prediction algorithm predicts structural progression in individuals with OA using only clinically available predictors supplemented by the M:L BMD ratio, a biomarker that could be made available at clinical sites.

Location-independent analysis of structural progression of osteoarthritis—Taking it all apart, and putting the puzzle back together makes the difference

The metric accepted by regulatory bodies for determining structural progression in clinical trials of knee osteoarthritis (OA) remains change in radiographic joint space width in the medial femorotibial compartment. However, magnetic resonance imaging has revealed that cartilage loss is spatially heterogeneous, and that it is enigmatic which knee will lose cartilage at which location. Whereas previous reviews have focused on imaging in general, the purpose of this particular perspective is to highlight availability and applications of location-independent analysis methodology in measuring structural progression in epidemiological and interventional clinical trials, and to highlight its specific advantages over existing methodologies. Narrative review/perspective based on a Pubmed search of original articles from 2009 to current. Ordering longitudinal change in subregion cartilage thickness by magnitude and direction, and averaging such ordered values or sums of negative and positive changes across knees is shown to be superior in detecting risk factors and interventional effects on structural progression of knee OA. Further, the methodology permits exploration of cartilage loss and gain simultaneously, phenomena that are missed when measurements are confined to cartilage volume or thickness loss in plates or compartments. Given spatial heterogeneity of cartilage loss in knee OA, location-independent analysis by MRI may provide opportunity for a paradigm shift. The authors recommend use of a location-independent metrices as the structural endpoints in epidemiological and intervention trials, particularly when examining anabolic and catabolic drug effects. Location-independent methods may be translated to analysis of cartilage composition and other articular tissues.

Does (change in) infra-patellar fat pad volume and MRI signal predict symptomatic and structural progression of knee osteoarthritis? – Data from the fNIH biomarker consortium cohort

Does (change in) infra-patellar fat pad volume and MRI signal predict symptomatic and structural progression of knee osteoarthritis? – Data from the fNIH biomarker consortium cohort

Baseline and persistent knee symptoms are independent predictors of structural progression of knee osteoarthritis

Baseline and persistent knee symptoms are independent predictors of structural progression of knee osteoarthritis

Relationship Between Medial Meniscal Extrusion and Cartilage Loss in Specific Femorotibial Subregions: Data From the Osteoarthritis Initiative.

Medial meniscal extrusion is known to be related to structural progression of knee osteoarthritis. However, it is unclear whether medial meniscal extrusion is more strongly associated with cartilage loss in certain medial femorotibial subregions than in others. Segmentation of the medial tibial and femoral cartilage (baseline; 1-year followup) and the medial meniscus (baseline) was performed in 60 participants with frequent knee pain (mean ± SD ages 61.3 ± 9.2 years, body mass index 31.3 ± 3.9 kg/m(2) ) and with unilateral medial radiographic joint space narrowing (JSN) grades 1-3, using double-echo steady-state magnetic resonance images. Medial meniscal extrusion distance and extrusion area (percentage) between the external meniscal and tibial margin at baseline, and longitudinal medial cartilage loss in 8 anatomic subregions were determined. A significant association (Pearson's correlation coefficient) was seen between medial meniscal extrusion area in JSN knees and cartilage loss over 1 year throughout the entire medial femorotibial compartment. The strongest correlation was with cartilage loss in the external medial tibia (r =-0.34, P < 0.01 in JSN; r =-0.30, P = 0.02 in knees without JSN). Medial meniscal extrusion was associated with subsequent medial cartilage loss. The external medial tibial cartilage may be particularly vulnerable to thinning once the meniscus extrudes and its surface is exposed to direct, nonphysiological, cartilage-to-cartilage contact.

Quantitative relationship of thigh adipose tissue with pain, radiographic status, and progression of knee osteoarthritis: longitudinal findings from the osteoarthritis initiative.

The aim of this study was to explore the relationship of thigh subcutaneous fat (SCF) and intermuscular fat (IMF) content with knee osteoarthritis (KOA) cross-sectionally and longitudinally, using quantitative magnetic resonance imaging. Specifically, we examined relationships with frequent knee pain, various radiographic strata, and structural progression status of KOA. Subjects who showed between-knee discordance of frequent versus no pain (n = 48), osteophyte versus no radiographic KOA (n = 55), and radiographic joint space narrowing versus no joint space narrowing (n = 44) were selected from the Osteoarthritis Initiative. Knees with structural progression of KOA (n = 23) were compared with knees without progression. Axial thigh magnetic resonance images were used to determine IMF and SCF. Differences between knees and between baseline and 2-year follow-up were examined using paired t tests. Women displayed similar amounts of IMF, but twice the SCF of men. Limbs of women with frequently painful knees had statistically significant greater IMF areas (+4.2%; P = 0.05) than contralateral pain-free limbs did. No significant cross-sectional differences were observed between other strata. Men with structural progression appeared to have a greater longitudinal increase in SCF (+13.2%; P < 0.05) than did men without progression (-1.9%), and women with progression appeared to have a greater increase in IMF (+11.6%) than did those without progression (+1.5%). In women, painful knees display greater IMF content than do contralateral pain-free knees. Other between-knee comparisons did not reveal a regional association between radiographic KOA and thigh adipose tissue status. Structural progression of KOA may be associated with greater longitudinal increases in SCF in men and greater increases of IMF in women, compared with nonprogressive controls.

The Influence of Joint Loading on Bone Marrow Lesions in the Knee

Background: Bone marrow lesions (BMLs) are considered as predictors of pain, disability, and structural progression of knee osteoarthritis. The relationship between knee loading and BMLs is not yet completely understood. Purpose: To summarize the available evidence regarding the relationship between joint loading and the prevalence and progression of BMLs in the tibiofemoral joint. Study Design: Meta-analysis. Methods: Three databases (PubMed, Web of Science, and The Cochrane Library) were systematically screened for studies encompassing BMLs and changes in knee loading. A methodological quality assessment was conducted, and a meta-analysis computing overall odds ratios (ORs) was performed where possible. Results: A total of 29 studies involving 7641 participants were included. Mechanical loading was categorized as body weight and composition, compartmental load, structural lesion, and physical activity. High compartmental loads and structural lesions increased the risk for BMLs (overall ORs ranging from 1.56 [95% CI, 1.13-2.15] to 8.2 [95% CI, 4.4-15.1]; P = .006). Body weight increased the risk for BMLs to a lesser extent (overall OR, 1.03; 95% CI, 1.01-1.05; P = .007). Contradictory results for the effect of physical activity on BMLs were found. Conclusion: Augmented compartmental loads and structural lesions increased the risk of the presence or progression of BMLs. Body weight increased the risk for BMLs to a lesser extent. Contradictory results for the effect of physical activity on BMLs may be explained by a dose-response relationship, knee alignment, and structural lesions. Clinical Relevance: It has been shown that unloading the knee temporarily may induce beneficial effects on osteoarthritis-related structural changes. Therefore, an early recognition of BMLs in the aging athlete’s knee may provide information to counter the onset and aggravation of symptomatic knee osteoarthritis by reducing the knee load.

Vigorous but not moderate physical activity is related to structural progression of knee osteoarthritis over one year

s / Osteoarthritis and Cartilage 22 (2014) S7–S56 S20 was significantly associated with MCID in WOMAC pain worsening (Table). Conclusions: While measures of sensitization are associated with knee OA pain presence and severity cross-sectionally, they were not related longitudinally to development of new pain symptoms over 2 years; however, this is difficult to properly assess without carefully evaluating descending inhibitory effects concurrently. Baseline presence of temporal summation at the wrist may be associated with pain worsening, suggesting a potential trait-like phenomenon for this finding, while baseline PPT was not. However, decreases in PPT (i.e., increase in mechanical hyperalgesia) over 2 years were associated with clinically meaningful increased pain severity, suggesting a state-like phenomenon. Enhanced pain sensitivity coinciding with new/increased knee pain may be mediated by sensitization or an imbalance between descending facilitation and inhibition. These results suggest that such changes may not necessarily precede development of knee pain, but may influence the experience of pain and its severity once pain has been established.

FRI0301 Role of vitamin D in osteoarthritis knee: A six month double blind, randomized, placebo control trial

BackgroundThere is a putative role of vitamin D in osteoarthritis (OA) based on animal, epidemiological and human clinical studies. Short term clinical studies suggest beneficial influence of vitamin D on...

Effect of bisphosphonate use in patients with symptomatic and radiographic knee osteoarthritis: data from the Osteoarthritis Initiative

ObjectivesBisphosphonates have some reported beneficial effects in treating osteoarthritis (OA). This study examined the effects of bisphosphonate use on symptoms and structural progression of knee OA in participants from the...