A Decline in Walking Speed is Associated with Incident Knee Replacement in Adults with and at Risk for Knee Osteoarthritis

OBJECTIVE: To determine if a one-year change in walking speed is associated with receiving an incident knee replacement during the following year in adults with and at risk for knee osteoarthritis (OA). METHODS: Using data from the Osteoarthritis Initiative, we determined a one-year change in 20- meter walk speed from three observation periods (i.e., 0-12, 12-24, and 24-36 month). We operationally defined one-year change in walking speed as either: 1) decline: \u3c -0.1 m/s change, 2) no change: between -0.1 and 0.1 m/s change, 3) increase: \u3e 0.1 m/s change. Incident knee replacement was defined using each subsequent one-year period (i.e., 12-24, 24- 36, and 36-48 month). Combining data from the three observation periods, we performed a Poisson regression with robust error variance to determine the relative risk between a change in walking speed (exposure) and incident knee replacement over the following year (outcome). RESULTS: Of the 4,264 participants included within this analysis (11,311 total person visits), 115 (3%) adults received a knee replacement. Decline in walking speed was associated with a 104% increase in risk [adjusted relative risk (RR)=2.04; 95% confidence interval (CI)= 1.40-2.98], while an increase in walking speed associated with a 55% decrease in risk (RR=0.45; 95% CI=0.22-0.93) of incident knee replacement in the following year compared to a person with no change in walking speed. CONCLUSION: A one-year decline in walking speed is associated with an increased risk, while one-year increase in walking speed is associated with a decreased risk of future incident knee replacement

Early pre-radiographic structural pathology precedes the onset of accelerated knee osteoarthritis.

BACKGROUND: Accelerated knee osteoarthritis (AKOA) is characterized by more pain, impaired physical function, and greater likelihood to receive a joint replacement compared to individuals who develop the typical gradual onset of disease. Prognostic tools are needed to determine which structural pathologies precede the development of AKOA compared to individuals without AKOA. Therefore, the purpose of this manuscript was to determine which pre-radiographic structural features precede the development of AKOA. METHODS: The sample comprised participants in the Osteoarthritis Initiative (OAI) who had at least one radiographically normal knee at baseline (Kellgren-Lawrence [KL] grade  3) and No AKOA. The index visit was the study visit when participants met criteria for AKOA or a matched timepoint for those who did not develop AKOA. Magnetic resonance (MR) images were assessed for 12 structural features at the OAI baseline, and 1 and 2 years prior to the index visit. Separate logistic regression models (i.e. OAI baseline, 1 and 2 years prior) were used to determine which pre-radiographic structural features were more likely to antedate the development of AKOA compared to individuals not developing AKOA. RESULTS: At the OAI baseline visit, degenerative cruciate ligaments (Odds Ratio [OR] = 2.2, 95% Confidence Interval [CI] = 1.3,3.5), infrapatellar fat pad signal intensity alteration (OR = 2.0, 95%CI = 1.2,3.2), medial/lateral meniscal pathology (OR = 2.1/2.4, 95%CI = 1.3,3.4/1.5,3.8), and greater quantitative knee effusion-synovitis (OR = 2.2, 95%CI = 1.4,3.4) were more likely to antedate the development of AKOA when compared to those that did not develop AKOA. These results were similar at one and two years prior to disease onset. Additionally, medial meniscus extrusion at one year prior to disease onset (OR = 3.5, 95%CI = 2.1,6.0) increased the likelihood of developing AKOA. CONCLUSIONS: Early ligamentous degeneration, effusion/synovitis, and meniscal pathology precede the onset of AKOA and may be prognostic biomarkers

Composite quantitative knee structure metrics predict the development of accelerated knee osteoarthritis:data from the osteoarthritis initiative

BACKGROUND: We aimed to determine if composite structural measures of knee osteoarthritis (KOA) progression on magnetic resonance (MR) imaging can predict the radiographic onset of accelerated knee osteoarthritis. METHODS: We used data from a nested case-control study among participants from the Osteoarthritis Initiative without radiographic KOA at baseline. Participants were separated into three groups based on radiographic disease progression over 4 years: 1) accelerated (Kellgren-Lawrence grades [KL] 0/1 to 3/4), 2) typical (increase in KL, excluding accelerated osteoarthritis), or 3) no KOA (no change in KL). We assessed tibiofemoral cartilage damage (four regions: medial/lateral tibia/femur), bone marrow lesion (BML) volume (four regions: medial/lateral tibia/femur), and whole knee effusion-synovitis volume on 3 T MR images with semi-automated programs. We calculated two MR-based composite scores. Cumulative damage was the sum of standardized cartilage damage. Disease activity was the sum of standardized volumes of effusion-synovitis and BMLs. We focused on annual images from 2 years before to 2 years after radiographic onset (or a matched time for those without knee osteoarthritis). To determine between group differences in the composite metrics at all time points, we used generalized linear mixed models with group (3 levels) and time (up to 5 levels). For our prognostic analysis, we used multinomial logistic regression models to determine if one-year worsening in each composite metric change associated with future accelerated knee osteoarthritis (odds ratios [OR] based on units of 1 standard deviation of change). RESULTS: Prior to disease onset, the accelerated KOA group had greater average disease activity compared to the typical and no KOA groups and this persisted up to 2 years after disease onset. During a pre-radiographic disease period, the odds of developing accelerated KOA were greater in people with worsening disease activity [versus typical KOA OR (95% confidence interval [CI]): 1.58 (1.08 to 2.33); versus no KOA: 2.39 (1.55 to 3.71)] or cumulative damage [versus typical KOA: 1.69 (1.14 to 2.51); versus no KOA: 2.11 (1.41 to 3.16)]. CONCLUSIONS: MR-based disease activity and cumulative damage metrics may be prognostic markers to help identify people at risk for accelerated onset and progression of knee osteoarthritis

Risk factors and the natural history of accelerated knee osteoarthritis: a narrative review.

BACKGROUND: Osteoarthritis is generally a slowly progressive disorder. However, at least 1 in 7 people with incident knee osteoarthritis develop an abrupt progression to advanced-stage radiographic disease, many within 12 months. We summarize what is known - primarily based on findings from the Osteoarthritis Initiative - about the risk factors and natural history of accelerated knee osteoarthritis (AKOA) - defined as a transition from no radiographic knee osteoarthritis to advanced-stage disease < 4 years - and put these findings in context with typical osteoarthritis (slowly progressing disease), aging, prior case reports/series, and relevant animal models. Risk factors in the 2 to 4 years before radiographic manifestation of AKOA (onset) include older age, higher body mass index, altered joint alignment, contralateral osteoarthritis, greater pre-radiographic disease burden (structural, symptoms, and function), or low fasting glucose. One to 2 years before AKOA onset people often exhibit rapid articular cartilage loss, larger bone marrow lesions and effusion-synovitis, more meniscal pathology, slower chair-stand or walking pace, and increased global impact of arthritis than adults with typical knee osteoarthritis. Increased joint symptoms predispose a person to new joint trauma, which for someone who develops AKOA is often characterized by a destabilizing meniscal tear (e.g., radial or root tear). One in 7 people with AKOA onset subsequently receive a knee replacement during a 9-year period. The median time from any increase in radiographic severity to knee replacement is only 2.3 years. Despite some similarities, AKOA is different than other rapidly progressive arthropathies and collapsing these phenomena together or extracting results from one type of osteoarthritis to another should be avoided until further research comparing these types of osteoarthritis is conducted. Animal models that induce meniscal damage in the presence of other risk factors or create an incongruent distribution of loading on joints create an accelerated form of osteoarthritis compared to other models and may offer insights into AKOA. CONCLUSION: Accelerated knee osteoarthritis is unique from typical knee osteoarthritis. The incidence of AKOA in the Osteoarthritis Initiative and Chingford Study is substantial. AKOA needs to be taken into account and studied in epidemiologic studies and clinical trials

Accelerated knee osteoarthritis is associated with pre-radiographic degeneration of the extensor mechanism and cruciate ligaments: data from the Osteoarthritis Initiative

Abstract: Background: To determine if adults with incident accelerated knee osteoarthritis (KOA) are more likely to have degenerative knee ligaments or tendons compared to individuals with typical or no KOA. Methods: We identified 3 sex-matched groups among Osteoarthritis Initiative participants who had a knee without radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2): 1) accelerated KOA: at least 1 knee had KL grade ≥ 3 in ≤48 months, 2) typical KOA: at least 1 knee increased in radiographic scoring within 48 months, 3) no KOA: both knees had the same KL grade at baseline and 48 months. We evaluated knee magnetic resonance images up to 2 years before and after a visit when the accelerated or typical KOA criteria were met (index visit). Radiologists reported degenerative signal changes for cruciate and collateral ligaments, and extensor mechanism and proximal gastrocnemius tendons. We used generalized linear mixed models with 2 independent variables: group and time. Results: Starting at least 2 years before onset, adults with accelerated KOA were twice as likely to have degenerative cruciate ligaments than no KOA (odds ratio = 2.10, 95% CI = 1.18, 3.74). A weaker association (not statistically significant) was detected for adults with accelerated versus typical KOA (OR = 1.72, 95%CI = 0.99, 3.02). Regardless of time, adults with accelerated (odds ratio = 2.13) or typical KOA (odds ratio = 2.16) were twice as likely to have a degenerative extensor mechanism than no KOA. No other structural features were statistically significant. Conclusions: Degenerative cruciate ligaments or extensor mechanism antedate radiographic onset of accelerated KOA. Hence, knee instability may precede accelerated KOA, which might help identify patients at high-risk for accelerated KOA and novel prevention strategies

Associations between knee kinematics during gait and quadriceps corticomotor excitability following anterior cruciate ligament reconstruction

American College of Sports MedicineBackground: Impaired quadriceps function is associated with a more extended knee throughout the stance phase of gait in individuals with anterior cruciate ligament reconstruction (ACLR). This stiffened knee strategy may alter tibiofemoral loading and hasten joint breakdown and osteoarthritis development. Altered quadriceps corticomotor excitability may influence knee kinematic during gait; yet it is unknown if quadriceps corticomotor excitability associates with gait kinematics. Purpose: To determine associations between quadriceps corticomotor excitability and sagittal plane knee kinematics during walking for ACLR individuals. Methods: Thirty-three individuals with unilateral ACLR participated in this cross-sectional study (72% female, 22.2 ± 3.5years; 72.5 ± 17.2kg; 1.7 ± 0.1m; 49.9 ± 40.4 months postACLR). Quadriceps corticomotor excitability was assessed as active motor threshold (AMT) from the vastus medialis of the ACLR limb using transcranial magnetic stimulation. Three dimensional biomechanics were collected during over ground walking at a self-selected speed and extracted from the first 50% of stance. We evaluated sagittal plane knee kinematics for the current study including (knee flexion angle at heel strike [HS]; peak knee flexion angle; knee flexion excursion [peak angle – HS angle]). Partial Pearson product-moment correlations were used to assess associations between kinematic variables and corticomotor variables in the ACLR limb controlling for gait speed (α = 0.05). Results: AMT was not associated with sagittal plane knee kinematics in the ACLR limb during walking (angle at HS r= -0.13 P=0.47; peak knee flexion angle r= -0.22 P=0.22; knee flexion excursion r= -0.19 P=0.29). Conclusions: No associations were found between quadriceps corticomotor excitability and sagittal plane knee kinematics during gait in individuals with ACLR. Central pattern generators, and not cortical excitability, may more strongly influence gait kinematics. Further work is necessary to determine the influence of altered corticomotor excitability on other gait outcomes including kinetics and lower limb muscle activity patterns.Science Foundation IrelandInsight Research Centr

Associations between knee kinematics during gait and quadriceps corticomotor excitability following anterior cruciate ligament reconstruction

American College of Sports MedicineBackground: Impaired quadriceps function is associated with a more extended knee throughout the stance phase of gait in individuals with anterior cruciate ligament reconstruction (ACLR). This stiffened knee strategy may alter tibiofemoral loading and hasten joint breakdown and osteoarthritis development. Altered quadriceps corticomotor excitability may influence knee kinematic during gait; yet it is unknown if quadriceps corticomotor excitability associates with gait kinematics. Purpose: To determine associations between quadriceps corticomotor excitability and sagittal plane knee kinematics during walking for ACLR individuals. Methods: Thirty-three individuals with unilateral ACLR participated in this cross-sectional study (72% female, 22.2 ± 3.5years; 72.5 ± 17.2kg; 1.7 ± 0.1m; 49.9 ± 40.4 months postACLR). Quadriceps corticomotor excitability was assessed as active motor threshold (AMT) from the vastus medialis of the ACLR limb using transcranial magnetic stimulation. Three dimensional biomechanics were collected during over ground walking at a self-selected speed and extracted from the first 50% of stance. We evaluated sagittal plane knee kinematics for the current study including (knee flexion angle at heel strike [HS]; peak knee flexion angle; knee flexion excursion [peak angle – HS angle]). Partial Pearson product-moment correlations were used to assess associations between kinematic variables and corticomotor variables in the ACLR limb controlling for gait speed (α = 0.05). Results: AMT was not associated with sagittal plane knee kinematics in the ACLR limb during walking (angle at HS r= -0.13 P=0.47; peak knee flexion angle r= -0.22 P=0.22; knee flexion excursion r= -0.19 P=0.29). Conclusions: No associations were found between quadriceps corticomotor excitability and sagittal plane knee kinematics during gait in individuals with ACLR. Central pattern generators, and not cortical excitability, may more strongly influence gait kinematics. Further work is necessary to determine the influence of altered corticomotor excitability on other gait outcomes including kinetics and lower limb muscle activity patterns.Science Foundation IrelandInsight Research Centr

Femoral Cartilage Ultrasound Echo Intensity Associates with Arthroscopic Cartilage Damage

This study compared quantitative cartilage ultrasound metrics between people with (n=12) and without (n=12) arthroscopic cartilage damage after anterior cruciate ligament injury (age, 24.9 +/- 3.7 y; sex, 33% female, 67% male; days since injury=50 +/- 52). A transverse suprapatellar ultrasound assessment imaged the femoral cartilage in participants\u27 injured knees before a clinical arthroscopy. A custom program automatically separated a manual cartilage segmentation into standardized medial and lateral femoral regions and calculated mean thickness (i.e., cross-sectional area/length of cartilage-bone interface), mean echo intensity and echo-intensity heterogeneity. An orthopedic surgeon assessed arthroscopic cartilage damage in the medial and lateral femoral condyles using the Outerbridge grading system (cartilage damage=Outerbridge \u3e /= 1). Separate logistic regressions for medial and lateral femoral cartilage were used to determine the association between each ultrasound metric and arthroscopic cartilage damage. In medial femoral cartilage, for every 1 standard deviation decrease in echo-intensity mean and heterogeneity, there is, respectively, a 91% (adjusted odds ratio, 0.09; 95% confidence interval, 0.01-0.69) and 97% (adjusted odds ratio, 0.03; 95% confidence interval, 0.002-0.50) increase in the odds of having arthroscopic cartilage damage. Lateral cartilage ultrasound metrics are not associated with lateral arthroscopic cartilage damage. This study provides preliminary evidence that femoral cartilage ultrasound echo intensity is a non-invasive measure associated with medial femoral cartilage health after anterior cruciate ligament injury

The Inverse OARSI-OMERACT Criteria Is a Valid Indicator of the Clinical Worsening of Knee Osteoarthritis: Data From the Osteoarthritis Initiative

OBJECTIVE: We assessed if the inverse Osteoarthritis Research Society International (OARSI) and Outcome Measures in Rheumatology (OMERACT) criteria relate to concurrent radiographic knee osteoarthritis (KOA) progression and decline in walking speed, as well as future knee replacement. METHODS: We conducted knee-based analyses of data from the Osteoarthritis Initiative. All knees had symptomatic OA: at least doubtful radiographic KOA (Kellgren-Lawrence grade \u3e /= 1) and knee pain \u3e /= 10/100 (Western Ontario and McMaster Universities Osteoarthritis Index pain) at the 12-month visit. The inverse of the OARSI-OMERACT responder criteria depended on knee pain and function, and global assessment of knee impact. We used generalized linear mixed models to assess the relationship of the inverse OARSI-OMERACT criteria over 2 years (i.e., 12-month and 36-month visits) with worsening radiographic severity (any increase in Kellgren-Lawrence grade from 12 months to 36 months) and decline in self-selected 20-m walking speed of \u3e /= 0.1m/s (from 12 months to 36 months). We used a Cox model to assess time to knee replacement during the 6 years after the 36-month visit as an outcome. RESULTS: Among the 1746 analyzed, 19% met the inverse OARSI-OMERACT criteria. Meeting the inverse OARSI-OMERACT criteria was associated with almost double the odds of experiencing concurrent worsening in radiographic KOA severity (OR 1.89, 95% CI 1.32-2.70) or decline in walking speed (OR 1.82, 95% CI 1.37-2.40). A knee meeting the inverse OARSI-OMERACT criteria was more likely to receive a knee replacement after the 36-month visit (23%) compared with a nonresponder (10%; HR 2.54, 95% CI 1.89-3.41). CONCLUSION: The inverse OARSI-OMERACT criteria for worsening among people with KOA had good construct validity in relation to clinically relevant outcomes

Radiomic features of the medial meniscus predicts incident destabilizing meniscal tears: Data from the osteoarthritis initiative

Publication status: PublishedFunder: Merck Research LaboratoriesFunder: Novartis Pharmaceuticals CorporationFunder: GlaxoSmithKlineFunder: Pfizer, IncAbstractThe objective of this study was to determine the optimal meniscal radiomic features to classify people who will develop an incident destabilizing medial meniscal tear. We used magnetic resonance (MR) images from an existing case–control study that includes images from the first 4 years of the Osteoarthritis Initiative (OAI). For this exploratory analysis (n = 215), we limited our study sample to people with (1) intact menisci at the OAI baseline visit, (2) 4‐year meniscal status data, and (3) complete meniscal data from each region of interest. Incident destabilizing meniscal tear was defined as progressing from an intact meniscus to a destabilizing tear by the 48‐month visit using intermediate‐weighted fat‐suppressed MR images. One reader manually segmented each participant's anterior and posterior horn of the medial menisci at the OAI baseline visit. Next, 61 different radiomic features were extracted from each medial meniscus horn. We performed a classification and regression tree (CART) analysis to determine the classification rules and important variables that predict incident destabilizing meniscal tear. The CART correctly classified 24 of the 34 cases and 172 out of 181 controls with a sensitivity of 70.6% and a specificity of 95.0%. The CART identified large zone high gray level emphasis (i.e., more coarse texture) from the posterior horn as the most important variable to classify who would develop an incident destabilizing medial meniscal tear. The use of radiomic features provides sensitive and quantitative measures of meniscal alterations, allowing us to intervene and prevent destabilizing meniscal tears.</jats:p