Tibiofemoral articular cartilage composition differs based on serum biochemical profiles following anterior cruciate ligament reconstruction.

OBJECTIVE: Biochemical joint changes contribute to posttraumatic osteoarthritis (PTOA) development following anterior cruciate ligament reconstruction (ACLR). The purpose of this longitudinal cohort study was to compare tibiofemoral cartilage composition between ACLR patients with different serum biochemical profiles. We hypothesized that profiles of increased inflammation (monocyte chemoattractant protein-1 [MCP-1]), type-II collagen turnover (type-II collagen breakdown [C2C]:synthesis [CPII]), matrix degradation (matrix metalloproteinase-3 [MMP-3] and cartilage oligomeric matrix protein [COMP]) preoperatively to 6-months post-ACLR would be associated with greater tibiofemoral cartilage T1ρ relaxation times 12-months post-ACLR. DESIGN: Serum was collected from 24 patients (46% female, 22.1 ± 4.2 years old, 24.0 ± 2.6 kg/m2 body mass index [BMI]) preoperatively (6.4 ± 3.6 days post injury) and 6-months post-ACLR. T1ρ Magnetic Resonance Imaging (MRI) was collected for medial and lateral tibiofemoral articular cartilage at 12-months post-ACLR. A k-means cluster analysis was used to identify profiles based on biomarker changes over time and T1ρ relaxation times were compared between cluster groups controlling for sex, age, BMI, concomitant injury (either meniscal or chondral pathology), and Marx Score. RESULTS: One cluster exhibited increases in MCP-1 and COMP while the other demonstrated decreases in MCP-1 and COMP preoperatively to 6-months post-ACLR. The cluster group with increases in MCP-1 and COMP demonstrated greater lateral tibial (adjusted mean difference = 3.88, 95% confidence intervals [1.97-5.78]) and femoral (adjusted mean difference = 12.71, 95% confidence intervals [0.41-23.81]) T1ρ relaxation times. CONCLUSION: Profiles of increased serum levels of inflammation and matrix degradation markers preoperatively to 6-months post-ACLR are associated with MRI changes consistent with lesser lateral tibiofemoral cartilage proteoglycan density 12-months post-ACLR.

Synovial fluid concentrations of matrix Metalloproteinase-3 and Interluekin-6 following anterior cruciate ligament injury associate with gait biomechanics 6 months following reconstruction.

OBJECTIVE: To compare gait biomechanics 6 months following anterior cruciate ligament (ACL) reconstruction (ACLR) between patients with the highest and lowest concentrations of synovial fluid (SF) interleukin-6 (IL-6) and matrix metalloproteinase-3 (MMP-3), as well as compared to uninjured controls. DESIGN: SF concentrations of IL-6 and MMP-3 were collected 7 ± 4 days post injury in 38 ACL injured patients (55% female, 21±4yrs, 25.3 ± 5.2BMI). ACL injured individuals were stratified into the lowest and highest quartiles based on IL-6 (IL-6Lowest and IL-6Highest) and MMP-3 (MMP-3Lowest and MMP-3Highest) concentrations. Gait biomechanics were collected on the injured limb 6 months post-ACLR and in 38 uninjured controls (50% female, 21±3yrs, 23.8 ± 2.8BMI). Functional analyses of variance were used to compare vertical ground reaction force (vGRF), knee flexion angle (KFA), and internal knee extension moment (KEM) waveforms throughout stance phase of gait to determine the proportions of stance differing between limbs and groups. RESULTS: Compared to uninjured controls, IL-6High and MMP-3High ACL subgroups demonstrated lesser vGRF (largest differences: IL-6, 7.88%BW; MMP-3, 11.05%BW) during early-stance and greater vGRF (largest differences: IL-6, 6.21%BW; MMP-3, 5.85%BW) in mid-stance, lesser KFA (largest differences: IL-6, 3.11°; MMP-3, 3.72°) and lesser KEM (largest differences: IL-6, 0.96%BW•m; MMP-3, 1.07%BW•m) in early-stance, as well as greater KFA in mid-stance (largest differences: IL-6, 1.5°; MMP-3, 2.95°). CONCLUSIONS: High SF concentrations of a proinflammatory cytokine and a degradative enzyme early post-ACL injury are associated with aberrant gait biomechanics in the injured limb at 6 months post-ACLR (i.e., lesser vGRF, KFA and KEM) linked to posttraumatic osteoarthritis development.

T1ρ MRI of the talar articular cartilage is increased in those with chronic ankle instability.

OBJECTIVE: To determine if individuals with chronic ankle instability (CAI) demonstrate different talar cartilage T1ρ relaxation times compared to uninjured controls. DESIGN: Fifteen CAI (21.13 ± 1.81 years, 4.00 ± 2.07 previous ankle sprains) and fifteen controls (21.07 ± 2.55 years, no previous ankle sprains) participated. CAI inclusion criteria was in accordance with the International Ankle Consortium guidelines. Greater T1ρ relaxation times were interpreted as greater degenerative changes. Participants were non-weight bearing for 30-minutes prior to scanning to unload the cartilage. Voxel by voxel T1ρ relaxation times were calculated from a five image sequence. Segmentation of the talar cartilage was performed manually using ITK-SNAP software. T1ρ relaxation time means and variability across the entire talus and in the anteromeidal, anterolateral, posteromedial, and posterolateral regions of interest (ROIs) were compared between groups using mean differences and effect sizes (ES) with their corresponding 95% confidence intervals (95%CI). RESULTS: Individuals with CAI demonstrated higher T1ρ relaxation times (mean ± standard deviation) across the entire talus (CAI: 65.97 ± 10.45 ms, Control: 58.84 ± 7.68 ms; ES = 0.76, 95%CI = 0.02-1.50), in the anterolateral (ES = 1.00, 95%CI = 0.24-1.48), posteromedial (ES = 0.74, 95%CI = 0.01-1.49), and posterolateral region of interest (ES = 3.84, 95%CI = 2.63-5.04). The T1ρ relaxation time variability (mean ± standard deviation) also differed across the overall talus (CAI: 32.78 ± 4.06 ms, Control: 28.23 ± 4.45 ms; ES = 1.04, 95%CI = 0.28-1.80), in the anteriolateral, (ES = 1.07, 95%CI = 0.31, 1.84) and posteriolateral (ES = 1.00, 95%CI = 0.24-1.75) ROIs. CONCLUSIONS: Individuals with CAI demonstrate greater T1ρ relaxation times and higher T1ρ variability compared to uninjured controls. This finding supports the existing literature illustrating early degenerative joint tissue changes consistent with early onset posttraumatic osteoarthritis in individuals with CAI.

Sagittal plane walking biomechanics in individuals with knee osteoarthritis after quadriceps strengthening.

OBJECTIVE: To compare sagittal walking gait biomechanics between participants with knee osteoarthritis (KOA) who increased quadriceps strength following a lower-extremity strengthening intervention (responders) and those who did not increase strength following the same strengthening protocol (non-responders) both at baseline and following the lower extremity strengthening protocol. DESIGN: Fifty-three participants with radiographic KOA (47% female, 62.3 ± 7.1 years, BMI = 28.5 ± 3.9 kg/m2) were enrolled in 10 sessions of lower extremity strengthening over a 28-day period. Maximum isometric quadriceps strength and walking gait biomechanics were collected on the involved limb at baseline and 4-weeks following the strengthening intervention. Responders were classified as individuals who increased quadriceps strength greater than the upper limit of the 95% confidence interval (CI) for the minimal detectable change (MDC) in quadriceps strength (29 Nm) determined in a previous study. 2 × 2 functional analyses of variance were used to evaluate the effects of group (responders and non-responders) and time (baseline and 4-weeks) on time-normalized waveforms for knee flexion angle (KFA), vertical ground reaction force (vGRF), and internal knee extension moment (KEM). RESULTS: A significant group x time interaction for KFA demonstrated greater KFA in the first half of stance at baseline and greater knee extension in the second half of stance at 4-weeks in responders compared to non-responders. There was no significant group x time interaction for vGRF or internal KEM. CONCLUSIONS: Quadriceps strengthening may be used to stimulate small changes in KFA in individuals with KOA.

Ultrasonographic assessment of medial femoral cartilage deformation acutely following walking and running.

OBJECTIVE: To determine the magnitude of medial femoral cartilage deformation using ultrasonography (US) following walking and running in healthy individuals. DESIGN: Twenty-five healthy participants with no history of osteoarthritis or knee injury volunteered for this study. Medial femoral cartilage thickness was assessed using US before and after three separate 30-min loading conditions: (1) walking at a self-selected speed, (2) running at a self-selected speed, and (3) sitting on a treatment table (i.e., control). Cartilage deformation was calculated as the percent change score from pre to post loading in each loading condition. The magnitude of cartilage deformation was compared between the three loading conditions. RESULTS: There was no difference in baseline cartilage thickness between the three sessions (F1,24 = 0.18, P = 0.68). Cartilage deformation was different between the loading conditions (F1,24 = 47.54, P < 0.001). The walking (%Δ = -6.7, t24 = 6.90, P < 0.001, d = -1.92) and running (%Δ = -8.9, t24 = 8.14, P < 0.001, d = -1.85) conditions resulted in greater cartilage deformation when compared to the control condition (%Δ = +3.4). There was no difference in cartilage deformation between the running and walking conditions (t24 = 1.10, P = 0.28, d = 0.33). US measured medial femoral cartilage thickness demonstrated reliability and precision within a single session (ICC2,k = 0.966, SEM = 0.07 mm) and between additional sessions separated by seven (ICC2,k = 0.964, SEM = 0.08 mm) and 16 days (ICC2,k = 0.919, SEM = 0.11 mm). CONCLUSIONS: US demonstrated to be a reliable and sensitive imaging modality at quantifying medial femoral cartilage deformation in healthy individuals. Both walking and running conditions created greater cartilage deformation when compared to the control conditions, but no difference was observed between the walking and running conditions.

Quantifying levels of function between different subgroups of chronic ankle instability.

The purpose of this original investigation was to determine if selected sensorimotor, mechanical, and self-reported measures are different among chronic ankle instability (CAI) subgroups, healthy control participants, and lateral ankle sprain copers (LAS-Copers). Ninety-four participants volunteered and were categorized into perceived ankle instability (PI) alone (n = 13), recurrent ankle sprains (RAS) alone (n = 12), PI in combination with RAS (PI-RAS; n = 25), LAS-Copers (n = 18), and controls (n = 26). Participants completed self-assessed global, regional, and psychological health-related quality-of-life (HRQOL) questionnaires and assessments of sensorimotor function and mechanical joint laxity. One-way ANOVAs were performed with the intention of reducing the number of original outcomes into a smaller number of predictor variables. Discriminant functional analysis was used to establish which specific measures best differentiate between groups. Eight outcome measures from neural excitability, postural control, static postural control, and HRQOL showed a significant differentiation between five groups (Wilk's λ = 0.26, χ232  = 114 45, P < 0.001, canonical correlation = 0.80) and correctly determined only 58.1% of group membership, and the PI-RAS and control groups were the only fit in the proposed model. A different model or other sensorimotor outcomes from more dynamic and complex tasks may be needed for the PI, RAS, and LAS-Coper groups.

Quadriceps neural alterations in anterior cruciate ligament reconstructed patients: A 6-month longitudinal investigation.

The purpose of this investigation was to evaluate differences in quadriceps corticospinal excitability, spinal-reflexive excitability, strength, and voluntary activation before, 2 weeks post and 6 months post-anterior cruciate ligament reconstruction (ACLr). This longitudinal, case-control investigation examined 20 patients scheduled for ACLr (11 females, 9 males; age: 20.9 ± 4.4 years; height:172.4 ± 7.5 cm; weight:76.2 ± 11.8 kg) and 20 healthy controls (11 females, 9 males; age:21.7 ± 3.7 years; height: 173.7 ± 9.9 cm; weight: 76.1 ± 19.7 kg). Maximal voluntary isometric contractions (MVIC), central activation ratio (CAR), normalized Hoffmann spinal reflexes, active motor threshold (AMT), and normalized motor-evoked potential (MEP) amplitudes at 120% of AMT were measured in the quadriceps muscle at the specific time points. ACLr patients demonstrated bilateral reductions in spinal-reflexive excitability compared with controls before surgery (P = 0.02) and 2 weeks post-surgery (P ≤ 0.001). ACLr patients demonstrated higher AMT at 6 months post-surgery (P ≤ 0.001) in both limbs. No MEP differences were detected. Quadriceps MVIC and CAR were lower in both limbs of the ACLr group before surgery and 6 months post-surgery (P ≤ 0.05) compared with controls. Diminished excitability of spinal-reflexive and corticospinal pathways are present at different times following ACLr and occur in combination with clinical deficits in quadriceps strength and activation. Early rehabilitation strategies targeting spinal-reflexive excitability may help improve postoperative outcomes, while later-stage rehabilitation may benefit from therapeutic techniques aimed at improving corticospinal excitability.

Osteoarthritis-related biomarkers following anterior cruciate ligament injury and reconstruction: a systematic review.

OBJECTIVE: There is an increased risk of developing knee osteoarthritis (OA) following anterior cruciate ligament (ACL) injury. Biomarkers may provide diagnostic, prognostic, or burden of disease indicators of OA before radiographic changes become apparent. Unfortunately, there has been no systematic review to clarify which biomarkers may be most informative following injury. Therefore, this review critically investigated existing studies of OA-related biomarkers in ACL-deficient (ACL-D) and reconstructed (ACL-R) patients to summarize the current evidence and identify knowledge gaps. DESIGN: A systematic review of the literature in Web of Science and PubMed databases (1960-June 2014) was performed. All English-language case-control and longitudinal studies assessing OA-related biomarkers in ACL-D and ACL-R patients were considered. Data regarding biomarker changes over time within ACL-D and ACL-R patients as well as differences in ACL-D/ACL-R patients compared with a control group were extracted from pertinent studies. RESULTS: A descriptive summary of 20 included studies was produced. In ACL-D patients compared with controls, synovial fluid biomarkers indicated elevated collagen turnover, while the inflammatory cytokine response was inconclusive. In ACL-R patients, serum concentrations indicated decreased collagen breakdown, but urine concentrations were indicative of greater collagen breakdown when compared to controls. Compared to preoperative values, the overall inflammatory cytokine response measured with synovial fluid biomarkers increased while plasma biomarkers did not change following reconstruction. CONCLUSION: Patients with ACL-D or ACL-R have altered biomarkers indicative of OA. More research with standardized reporting is needed to effectively determine which biomarkers are the most indicative for OA development and progression following ACL injury.