Association between knee inflammation and knee pain in patients with knee osteoarthritis: a systematic review.

OBJECTIVE: To systematically review the literature on the relationship between markers of inflammation and pain in patients with knee osteoarthritis (OA). METHODS: We searched MEDLINE, Web of Science and EMBASE databases from inception until June 2021. Eligible articles had to report on the association between inflammation (as measured by effusion, synovitis, baker's cysts, cytokines and C-reactive protein) and pain in patients with radiographic knee OA. Two reviewers independently performed a screening on title and abstracts, data extraction and risk of bias assessment using the Newcastle-Ottawa Scale (NOS). A best evidence synthesis was conducted for each inflammatory sign included in this review. RESULTS: 37 studies were included. Articles reported on the following measures: effusion or synovitis assessed via ultrasound (n = 9) or magnetic resonance imaging (MRI) (n = 17); baker's cyst (n = 3); cytokine concentrations (n = 11); and C-reactive protein levels (n = 4). The strength of the association between inflammation and pain does not exceed the moderate level (i.e., correlation coefficient values ranging from 0.19 to 0.61). Moderate levels of evidence were found for the association between synovitis (measured with ultrasound or contrast enhanced MRI) and pain. The levels of evidence between effusion (assessed via ultrasound), effusion/synovitis (assessed via non-contrast enhanced MRI), Baker's cyst, cytokines, C-reactive protein and pain were conflicting. CONCLUSIONS: Different inflammatory markers are associated with pain but the correlation ranges from weak to moderate, and the quality of evidence from conflicting to moderate. Further research is needed to strengthen the level of evidence and to establish mechanisms.

Effect of cane use on bone marrow lesion volume in people with medial tibiofemoral knee osteoarthritis: randomized clinical trial.

OBJECTIVE: To evaluate effects of daily cane use for 3 months on medial tibiofemoral bone marrow lesion (BML) volumes in people with medial tibiofemoral osteoarthritis (OA). DESIGN: In this randomized controlled trial (RCT), 79 participants with medial tibiofemoral OA were randomized to either a cane group (using a cane whenever walking) or control group (not using any gait aid) for 3 months. The cane group received a single training session by a physiotherapist, using a biofeedback cane to teach optimal technique and body weight support and motor learning principles to facilitate retention of learning. The primary outcome was change in total medial tibiofemoral BML volume (per unit bone volume) measured from magnetic resonance imaging (MRI) at 3 months. Secondary outcomes were BML volumes (per unit bone volume) of the medial tibia and femur, and patient-reported outcomes of overall knee pain, knee pain on walking, physical function, perceived global symptom changes and health-related quality of life. MRI analyses were performed by a blinded assessor. RESULTS: Seventy-eight participants (99%) completed the primary outcome. Mean (standard deviation) daily cane use was 2.3 (1.7) hours over 3 months. No evidence of between-group differences was found for change in total medial tibiofemoral BML volume (mean difference: -0.0010 (95% confidence intervals: -0.0022, 0.0003)). Most secondary outcomes showed minimal differences between groups. CONCLUSION: Daily use of a cane during walking for 3 months aiming to reduce knee joint loading did not change medial tibiofemoral BML volumes compared to no use of gait aids. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ACTRN12614000909628).

Associations between changes in knee pain location and clinical symptoms in people with medial knee osteoarthritis using footwear for self-management: an exploratory study.

OBJECTIVE: To examine whether change in pain location is associated with clinically-relevant improvements in walking pain severity and physical dysfunction in people with medial tibiofemoral osteoarthritis (OA) using footwear for self-management. DESIGN: We analysed a sub-set of 91 participants pooled from both arms of a 6-month randomised controlled trial of footwear for knee OA. The Photographic Knee Pain Map was self-administered to generate changes in the number of painful zones ('unchanged', 'increased', 'decreased') and anatomical patterns of pain ('unchanged', 'no longer diffuse', 'becoming diffuse', 'other pattern changes'). Improvement in symptoms was determined using the minimum clinically important differences (MCIDs) in pain severity on a numeric rating scale, and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Fisher's exact tests examined differences in symptom improvement across categories of change and odds ratios (ORs, 95% CI) were calculated (adjusted for treatment allocation). RESULTS: Seventy-four percent (n = 67) of participants reported a change in pain location, and 46-50% (n = 42-45) reported clinically-relevant improvements in pain and function respectively. Fewer participants 'becoming diffuse' reported improved pain (n = 0, 0%) when compared to the other pattern change categories (P = 0.012). Participants with 'no longer diffuse' (OR (95% CI) = 0.3 (0.1-0.9) or 'becoming diffuse' (OR (95% CI) = 0.0 (0.0-0.4) pain patterns had significantly lower odds of improved function than those with 'other pattern changes'. CONCLUSION: Participants either developing into, or changing from, diffuse pain patterns were less likely to experience improvement in pain and/or function when self-managing with footwear.

Location of knee pain in medial knee osteoarthritis: patterns and associations with self-reported clinical symptoms.

OBJECTIVES: To (1) document pain location in medial tibiofemoral osteoarthritis (OA) using the patient-administered Photographic Knee Pain Map (PKPM); (2) compare pain severity, nature and likelihood of neuropathic-like symptoms, physical dysfunction and presence of symptoms at other sites across the most common pain patterns. DESIGN: Baseline data were analysed from 164 participants with medial tibiofemoral OA (TFJOA) participating in a randomised controlled trial (RCT). Participants completed the PKPM indicating all relevant pain zones of their most painful knee. Pain zones were collapsed into regions to determine patterns of pain. Symptoms were quantified using numeric rating scales (NRSs) of pain severity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Intermittent and Constant Osteoarthritis Pain (ICOAP) and painDETECT questionnaires. Symptoms at other joints were categorised as present/absent. RESULTS: The medial joint line (n = 123, 75%), patellar tendon (n = 62, 38%) and posterior knee (n = 61, 37%) were the most frequently reported pain zones. The most frequent patterns were diffuse (41%), isolated medial (16%), anterior-medial (12%) and medial-posterior (11%) pain. WOMAC and ICOAP scores were higher in the diffuse compared to anterior-medial patterns. Mean PainDETECT scores were higher with both diffuse and medial-posterior pain relative to anterior-medial pain. CONCLUSION: Only 16% of the cohort indicated isolated medial knee pain, whilst a diffuse pain pattern was most common. People with diffuse knee pain reported more severe pain and physical dysfunction than those with anterior-medial pain. Prevalence of possible/likely neuropathic-like symptoms tended to be more frequent in diffuse and posterior-medial patterns compared to anterior-medial pain.

Cartilage adaptation after anterior cruciate ligament injury and reconstruction: implications for clinical management and research? A systematic review of longitudinal MRI studies.

OBJECTIVE: To summarize the current evidence of magnetic resonance imaging (MRI)-measured cartilage adaptations following anterior cruciate ligament (ACL) reconstruction and of the potential factors that might influence these changes, including the effect of treatment on the course of cartilage change (i.e., surgical vs non-surgical treatment). METHODS: A literature search was conducted in seven electronic databases extracting 12 full-text articles. These articles reported on in vivo MRI-related cartilage longitudinal follow-up after ACL injury and reconstruction in "young" adults. Eligibility and methodological quality was rated by two independent reviewers. A best-evidence synthesis was performed for reported factors influencing cartilage changes. RESULTS: Methodological quality was heterogenous amongst articles (i.e., score range: 31.6-78.9%). Macroscopic changes were detectable as from 2 years follow-up next to or preceded by ultra-structural and functional (i.e., contact-deformation) changes, both in the lateral and medial compartment. Moderate-to-strong evidence was presented for meniscal lesion or meniscectomy, presence of bone marrow lesions (BMLs), time from injury, and persisting altered biomechanics, possibly affecting cartilage change after ACL reconstruction. First-year morphological change was more aggravated in ACL reconstruction compared to non-surgical treatment. CONCLUSION: In view of osteoarthritis (OA) prevention after ACL reconstruction, careful attention should be paid to the rehabilitation process and to the decision on when to allow return to sports. These decisions should also consider cartilage fragility and functional adaptations after surgery. In this respect, the first years following surgery are of paramount importance for prevention or treatment strategies that aim at impediment of further matrix deterioration. Considering the low number of studies and the methodological caveats, more research is needed.

Effects of in vivo exercise on ankle cartilage deformation and recovery in healthy volunteers: an experimental study.

OBJECTIVE: To monitor ankle cartilage 3D volume changes after in vivo exercise and during recovery. METHOD: Based on 3D MRI, 3D volumes of talar and tibial cartilage were calculated before and after 30 bilateral knee bends in 12 healthy volunteers. 3D volumes were calculated at five time points (one pre- and four post-scans) determining deformation and recovery for both cartilage plates of interest. Post-scans ran immediately after the exercise and were repeated according to a 15 min interval. 3D volumes were subjected to repeated measures GLM. Additionally, relative surface area use during deformation was compared between plates using a Wilcoxon Signed Ranks test and its correlation with deformation was investigated using Spearman's rho. RESULTS: Mean 3D volume change percentages for talar cartilage after the exercise were: -10.41%, -8.18%, -5.61% and -3.90%. For tibial cartilage mean changes were: -5.97%, -5.75%, +0.89% and +1.51%. For talar cartilage changes were significant, except following 30 min post-exercise. For tibial cartilage no changes were significant. At all time points, no significant differences in relative volume changes between both cartilage plates existed. Although no significant differences in relative surface area use between plates were revealed, a moderate to strong correlation with deformation existed. CONCLUSION: Ankle cartilage endures substantial deformation after in vivo loading that was restored within 30 min for the talus. Overall cartilage contact area involvement might be associated with cartilage quality maintenance in the upper ankle. Talar cartilage is suggested to play a critical role in intra-articular shock attenuation when compared to tibial cartilage.

Functional adaptation of knee cartilage in asymptomatic female novice runners compared to sedentary controls. A longitudinal analysis using delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC).

OBJECTIVE: To longitudinally estimate the change in glycosaminoglycan content of knee cartilage in asymptomatic untrained female novice runners participating in a Start To Run program (STR) compared to sedentary controls. METHOD: Nine females enrolling in a 10-week STR and 10 sedentary controls participated voluntarily. Prior to and after the 10-week period, both groups were subjected to dGEMRIC imaging. dGEMRIC indices of knee cartilage were determined at baseline and for the change after the 10-week period in both groups. Based on a self-reported weekly log, physical activity change during the study was depicted as decreased, unchanged or increased. The Mann-Whitney U and Kruskal-Wallis tests were applied to test the hypotheses that dGEMRIC changes occurred between groups and according to physical activity changes respectively. RESULTS: No significant differences were established between groups for dGEMRIC indices at baseline (P=0.541). A significant positive change of the median dGEMRIC index in the runners group was demonstrated when compared to the controls [+11.66ms (95% CI: -25.29, 44.43) vs -9.56ms (95% CI: -29.55, 5.83), P=0.006]. The change in dGEMRIC index differed significantly according to physical activity change (P=0.014), showing an increase in dGEMRIC index with increasing physical activity. CONCLUSION: Since cartilage appears to positively respond to moderate running when compared to a sedentary lifestyle, this running scheme might be considered a valuable tool in osteoarthritis prevention strategies. Caution is warranted when applying these results to a wider population and to longer training periods.

A prospective study on gait-related intrinsic risk factors for lower leg overuse injuries.

OBJECTIVE: To determine prospectively gait-related risk factors for lower leg overuse injury (LLOI). DESIGN: A prospective cohort study. SETTING: Male and female recruits from a start-to-run (STR) programme during a 10-week training period. PARTICIPANTS: 131 healthy subjects (20 men and 111 women), without a history of any lower leg complaint, participated in the study. INTERVENTIONS: Before the start of the 10-week STR programme, plantar force measurements during running were performed. During STR, lower leg injuries were diagnosed and registered by a sports physician. MAIN OUTCOME MEASURES: Plantar force measurements during running were performed using a footscan pressure plate. RESULTS: During the STR, 27 subjects (five men and 22 women) developed a LLOI. Logistic regression analysis revealed that subjects who developed a LLOI had a significantly more laterally directed force distribution at first metatarsal contact and forefoot flat, a more laterally directed force displacement in the forefoot contact phase, foot flat phase and at heel-off. These subjects also had a delayed change of the centre of force (COF) at forefoot flat, a higher force and loading underneath the lateral border of the foot, and a significantly higher directed force displacement of the COF at forefoot flat. CONCLUSIONS: These findings suggest that a less pronated heel strike and a more laterally directed roll-off can be considered as risk factors for LLOI. Clinically, the results of this study can be considered important in identifying individuals at risk of LLOI.