Modifying loading during gait leads to biochemical changes in serum cartilage oligomeric matrix protein concentrations in a subgroup of individuals with anterior cruciate ligament reconstruction.

PURPOSE: Strong observational evidence has linked changes in limb loading during walking following anterior cruciate ligament reconstruction (ACLR) to posttraumatic osteoarthritis (PTOA). It remains unknown if manipulating peak loading influences joint tissue biochemistry. Thus, the purpose of this study is to determine whether manipulating peak vertical ground reaction force (vGRF) during gait influences changes in serum cartilage oligomeric matrix protein (sCOMP) concentrations in ACLR participants. METHODS: Forty ACLR individuals participated in this randomized crossover study (48% female, age = 21.0 ± 4.4 years, BMI = 24.6 ± 3.1). Participants attended four sessions, wherein they completed one of four biofeedback conditions (habitual loading (no biofeedback), high loading (5% increase in vGRF), low loading (5% decrease in vGRF), and symmetrical loading (between-limb symmetry in vGRF)) while walking on a treadmill for 3000 steps. Serum was collected before (baseline), immediately (acute post), 1 h (1 h post), and 3.5 h (3.5 h post) following each condition. A comprehensive general linear mixed model was constructed to address the differences in sCOMP across all conditions and timepoints in all participants and a subgroup of sCOMP Increasers. RESULTS: No sCOMP differences were found across the entire cohort. In the sCOMP Increasers, a significant time × condition interaction was found (F9,206 = 2.6, p = 0.009). sCOMP was lower during high loading than low loading (p = 0.009) acutely (acute post). At 3.5 h post, sCOMP was higher during habitual loading than symmetrical loading (p = 0.001). CONCLUSION: These data suggest that manipulating lower limb loading in ACLR patients who habitually exhibit an acute increase in sCOMP following walking results in improved biochemical changes linked to cartilage health. Key Points • This study assesses the mechanistic link between lower limb load modification and joint tissue biochemistry at acute and delayed timepoints. • Real-time biofeedback provides a paradigm to experimentally assess the mechanistic link between loading and serum biomarkers. • Manipulating peak loading during gait resulted in a metabolic effect of lower sCOMP concentrations in a subgroup of ACLR individuals. • Peak loading modifications may provide an intervention strategy to mitigate the development of PTOA following ACLR.

Sustained Limb-Level Loading: A Ground Reaction Force Phenotype Common to Individuals at High Risk for and Those With Knee Osteoarthritis.

OBJECTIVE: The objective of this study was to compare the vertical (vGRF), anterior-posterior (apGRF), and medial-lateral (mlGRF) ground reaction force (GRF) profiles throughout the stance phase of gait (1) between individuals 6 to 12 months post-anterior cruciate ligament reconstruction (ACLR) and uninjured matched controls and (2) between ACLR and individuals with differing radiographic severities of knee osteoarthritis (KOA), defined as Kellgren and Lawrence (KL) grades KL2, KL3, and KL4. METHODS: A total of 196 participants were included in this retrospective cross-sectional analysis. Gait biomechanics were collected from individuals 6 to 12 months post-ACLR (n = 36), uninjured controls matched to the ACLR group (n = 36), and individuals with KL2 (n = 31), KL3 (n = 67), and KL4 osteoarthritis (OA) (n = 26). Between-group differences in vGRF, apGRF, and mlGRF were assessed in reference to the ACLR group throughout each percentage of stance phase using a functional linear model. RESULTS: The ACLR group demonstrated lower vGRF and apGRF in early and late stance compared to the uninjured controls, with large effects (Cohen's d range: 1.35-1.66). Conversely, the ACLR group exhibited greater vGRF (87%-90%; 4.88% body weight [BW]; d = 0.75) and apGRF (84%-94%; 2.41% BW; d = 0.79) than the KL2 group in a small portion of late stance. No differences in mlGRF profiles were observed between the ACLR and either the uninjured controls or the KL2 group. The magnitude of difference in GRF profiles between the ACLR and OA groups increased with OA disease severity. CONCLUSION: Individuals 6 to 12 months post-ACLR exhibit strikingly similar GRF profiles as individuals with KL2 KOA, suggesting both patient groups may benefit from targeted interventions to address aberrant GRF profiles.

Delayed cartilage oligomeric matrix protein response to loading is associated with femoral cartilage composition post-ACLR.

PURPOSE: To determine associations between immediate and delayed response of serum cartilage oligomeric matrix protein (sCOMP) to loading (i.e., 3000 walking steps) and femoral cartilage interlimb T1ρ relaxation times in individual's post-anterior cruciate ligament reconstruction (ACLR). METHODS: This cross-sectional study included 20 individuals 6-12 months following primary ACLR (65% female, 20.5 ± 4.0 years old, 24.9 ± 3.0 kg/m2, 7.3 ± 1.5 months post-ACLR). Serum samples were collected prior to, immediately following, and 3.5 h following walking 3000 steps on a treadmill at habitual walking speed. sCOMP concentrations were processed using enzyme-linked immunosorbent assays. Immediate and delayed absolute sCOMP responses to loading were evaluated immediately and 3.5 h post-walking, respectively. Participants underwent bilateral magnetic resonance imaging with T1ρ sequences to calculate resting femoral cartilage interlimb T1ρ relaxation time ratios between limbs (i.e., ACLR/Uninjured limb). Linear regression models were fitted to determine associations between sCOMP response to loading and femoral cartilage T1ρ outcomes controlling for pre-loading sCOMP concentrations. RESULTS: Greater increases in delayed sCOMP response to loading were associated with greater lateral (∆R2 = 0.29, p = 0.02) but not medial (∆R2 < 0.01, p = 0.99) femoral cartilage interlimb T1ρ ratios. Associations between immediate sCOMP response to loading with femoral cartilage interlimb T1ρ ratios were weak and non-significant (∆R2 range = 0.02-0.09, p range = 0.21-0.58). CONCLUSION: Greater delayed sCOMP response to loading, a biomarker of cartilage breakdown, is associated with worse lateral femoral cartilage composition in the ACLR limb compared to the uninjured limb. Delayed sCOMP response to loading may be a more indicative metabolic indicator linked to deleterious changes in composition than immediate sCOMP response.

Knee kinetics and the medial femoral cartilage cross-sectional area response to loading in indviduals with anterior cruciate ligament reconstruction.

BACKGROUND: Ultrasonography is capable of detecting morphological changes in femoral articular cartilage cross-sectional area in response to an acute bout of walking; yet, the response of femoral cartilage cross-sectional area varies between individuals. It is hypothesized that differences in joint kinetics may influence the response of cartilage to a standardized walking protocol. Therefore, the study purpose was to compare internal knee abduction and extension moments between individuals with anterior cruciate ligament reconstruction who demonstrate an acute increase, decrease, or unchanged medial femoral cross-sectional area response following 3000 steps. METHODS: The medial femoral cartilage in the anterior cruciate ligament reconstructed limb was assessed with ultrasonography before and immediately following 3000 steps of treadmill walking. Knee joint moments were calculated in the anterior cruciate ligament reconstructed limb and compared between groups throughout the stance phase of gait using linear regression and functional, mixed effects waveform analyses. FINDINGS: No associations between peak knee joint moments and the cross-sectional area response were observed. The group that demonstrated an acute cross-sectional area increase exhibited 1) lower knee abduction moments in early stance in comparison to the group that exhibited a decreased cross-sectional area response; and 2) greater knee extension moments in early stance in comparison to the group with an unchanged cross-sectional area response. INTERPRETATION: The propensity of femoral cartilage to acutely increase cross-sectional area in response to walking is consistent with less-dynamic knee abduction and knee extension moment profiles.

Walking speed does not affect net vastus lateralis fascicle length change on average during weight acceptance.

Faster walking speeds increase the demand on quadriceps muscles to produce adequate force to decelerate body mass and control knee flexion. Quadriceps fascicle behavior (i.e., fascicle length changes) influences force generation, which in turn affects mechanical loading of the articular cartilage during walking and the biochemical environment of the knee joint. The fascicle behavior underlying different walking speeds remains unclear but should be characterized to better understand how the quadriceps muscles accommodate faster walking speeds, speeds that often associate with better cartilage health outcomes. Our purpose was to quantify quadriceps muscle net fascicle length change during weight acceptance across a range of walking speeds in the context of more well-documented changes in muscle activity and knee joint moments. We hypothesized that vastus lateralis (VL) fascicles in healthy young adults would produce force with more overall lengthening in early stance at faster walking speeds with concomitant increases in muscle-tendon unit (MTU) lengthening, internal peak knee extensor moment (pKEM), vertical ground reaction force (GRF), and muscle activity. Participants walked for two-minute trials at their preferred speed and at 0.75 m/s and 1.75 m/s. We found that on average, the VL accommodates the greater mechanical demands of walking at faster speeds with greater muscle activity and while resisting muscle lengthening behavior. We infer then that tendon stretch accommodates MTU lengthening in healthy young adults across a range of speeds and suggest these results motivate additional studies aimed at evaluating VL fascicle behavior individuals with known quadriceps strength deficits, inhibition, or heightened risk for developing osteoarthritis.

Quadriceps Muscle Action and Association With Knee Joint Biomechanics in Individuals with Anterior Cruciate Ligament Reconstruction.

Insufficient quadriceps force production and altered knee joint biomechanics after anterior cruciate ligament reconstruction (ACLR) may contribute to a heightened risk of osteoarthritis. Quadriceps muscle lengthening dynamics affect force production and knee joint loading; however, no study to our knowledge has quantified in vivo quadriceps dynamics during walking in individuals with ACLR or examined correlations with joint biomechanics. Our purpose was to quantify bilateral vastus lateralis (VL) fascicle length change and the association thereof with gait biomechanics during weight acceptance in individuals with ACLR. The authors hypothesized that ACLR limbs would exhibit more fascicle lengthening than contralateral limbs. The authors also hypothesized that ACLR limbs would exhibit positive correlations between VL fascicle lengthening and knee joint biomechanics during weight acceptance in walking. The authors quantified VL contractile dynamics via cine B-mode ultrasound imaging in 18 individuals with ACLR walking on an instrumented treadmill. In partial support of our hypothesis, ACLR limb VL fascicles activated without length change on average during weight acceptance while fascicle length on the contralateral limb decreased on average. The authors found a positive association between fascicle lengthening and increase in knee extensor moments in both limbs. Our results suggest that examining quadriceps muscle dynamics may elucidate underlying mechanisms relevant to osteoarthritis.

The effects of knee extensor moment biofeedback on gait biomechanics and quadriceps contractile behavior.

Individuals with knee joint pathologies exhibit quadriceps dysfunction that, during walking, manifests as smaller peak knee extensor moment (pKEM) and reduced knee flexion excursion. These changes persist despite muscle strengthening and may alter stance phase knee joint loading considered relevant to osteoarthritis risk. Novel rehabilitation strategies that more directly augment quadriceps mechanical output during functional movements are needed to reduce this risk. As an important first step, we tested the efficacy of real-time biofeedback during walking to prescribe changes of ±20% and ±40% of normal walking pKEM values in 11 uninjured young adults. We simultaneously recorded knee joint kinematics, ground reaction forces, and, via ultrasound, vastus lateralis (VL) fascicle length change behavior. Participants successfully responded to real-time biofeedback and averaged up to 55% larger and 51% smaller than normal pKEM values with concomitant and potentially favorable changes in knee flexion excursion. While the VL muscle-tendon unit (MTU) lengthened, VL fascicles accommodated weight acceptance during walking largely through isometric, or even slight concentric, rather than eccentric action as is commonly presumed. Targeted pKEM biofeedback may be a useful rehabilitative and/or scientific tool to elicit desirable changes in knee joint biomechanics considered relevant to the development of osteoarthritis.