Impact of physical activity and mechanical loading on biomarkers typically used in osteoarthritis assessment: current concepts and knowledge gaps.

There is an ongoing need to develop prognostic and diagnostic biomarkers for osteoarthritis (OA). Understanding how biomarkers change in response to physical activity may be vital for understanding if a patient has a joint that is failing to adapt to a given loading stimulus. The purpose of this review is to describe how biomarker changes after joint loading may help detect early OA and determine prognosis. This may help to inform and more specifically target interventions and clinical trials. We conducted a critical review of the relevant literature that was published to January 2016. There is extensive OA biomarker research, specifically basal biomarker concentrations; however, there is limited research surrounding biomarker response to load. Some of this limited research includes the response of minimal biomarkers reflecting bone, synovium, inflammatory, and cartilage responses to load. Biomarker changes occur in bone and cartilage in response to a variety of activities and are influenced by variables such as body weight, load, vibration, and activity time. Biomarker responses to loading tasks may serve as a measure of overall joint health and be predictive of structural changes. Biomarkers adapt to training over time, and this may indicate a need for a gradual return to physical activity after an injury to allow time for joint tissues to adapt to load. Biomarker responses to physical activity may be monitored to determine appropriate loading levels and safety for return to activity.

Prevalence of Radiographic Knee Osteoarthritis After Anterior Cruciate Ligament Reconstruction, With or Without Meniscectomy: An Evidence-Based Practice Article.

Reference: Claes S, Hermie L, Verdonk R, Bellemans J, Verdonk P. Is osteoarthritis an inevitable consequence of anterior cruciate ligament reconstruction? A meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2013;21(9):1967-1976. CLINICAL QUESTION: What is the prevalence of radiographic knee osteoarthritis (OA) at a mean follow-up equal to or greater than 10 years after autologous anterior cruciate ligament (ACL) reconstruction, with or without meniscectomy? DATA SOURCES: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were used to conduct this meta-analysis. Studies were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane Library dating from their earliest file until October 2010. Key terms applied for searching were anterior cruciate ligament or ACL, autologous, follow-up, long-term, outcome, reconstruction, results, treatment, and (osteo)arthritis or osteoarthrosis. The reference lists of included studies were also manually checked to ensure that relevant articles were not omitted. STUDY SELECTION: The authors limited their search to English- and French-language journals. Included studies provided radiographic outcomes after autologous ACL reconstruction and had a mean follow-up of ≥10 years. Excluded studies evaluated ACL reconstruction with major concomitant surgical procedures (eg, meniscal allograft transplantation, high tibial osteotomy). In addition, data from 2 studies completed by the same research team with identical patient populations were limited to the article with the longest follow-up. Finally, manuscripts with inaccurate or incomplete data were excluded. DATA EXTRACTION: The following key characteristics of each study were extracted: type of study (prospective or retrospective); ACL surgical procedure (eg, open or arthroscopic bone-patellar tendon-bone graft); time frame of surgery; mean follow-up (in years) post-ACL reconstruction; total number of participants with radiographs; total number of participants with radiographic OA at follow-up; and number of participants with meniscectomy before, during, or after ACL reconstruction. Although the OA diagnosis was based on radiographic criteria, the included studies used 4 OA classifications and grading scales: Ahlbäck, Fairbanks, Kellgren and Lawrence, and International Knee Documentation Committee. Regardless of classification or grading scale, OA was defined as the presence of joint-space narrowing: Ahlbäck grades 1 through 5, modified Fairbanks grades 2 and 3, Kellgren and Lawrence ≥2, and International Knee Documentation Committee grades C and D. Tibiofemoral and patellofemoral OA data were collapsed due to the lack of reporting specificity among the studies. Participants were categorized into a meniscectomy or nonmeniscectomy group if this information was reported. Partial or total meniscectomies before, during, or after ACL reconstruction were collapsed regardless of location (medial or lateral compartment), and those patients who underwent a meniscal repair were grouped into the nonmeniscectomy group. Data were analyzed using odds ratios, the Cochran χ2 test, and a random-effects meta-regression analysis. The DerSimonian and Laird approach was used to assess study heterogeneity. P values below .05 were considered statistically significant. MAIN RESULTS: The initial computerized database search resulted in 211 possible studies. However, after the authors applied the inclusionary and exclusionary criteria, only 16 studies were relevant. A total of 1554 participants were available at the follow-up period. Mean follow-up ranged from 10 to 24.5 years; 11 of the 16 articles had a mean follow-up between 10 and 12 years. Heterogeneity was large (I2 = 96%), which indicated that the included studies generated a wide range of knee OA prevalence (2%-79%). Almost 28% (95% confidence interval [CI] = 16.3%, 43.5%) of participants had radiographic knee OA. A total of 1264 participants were involved in studies that evaluated meniscectomies (n = 11). Among the 614 participants with either partial or total meniscectomies, 50.4% had radiographic knee OA (95% CI = 27.4%, 73.1%). In contrast, only 16.4% (95% CI = 7.0%, 33.9%) of those without a meniscectomy had radiographic knee OA. CONCLUSIONS: The findings of Claes et al reflected a radiographic knee OA prevalence at a minimum average of 10 years' postautologous ACL reconstruction that was lower than commonly perceived (up to 79%). In addition, meniscectomy was an important risk factor (3.54-fold increase) for developing OA after ACL reconstruction.

Tibiofemoral Osteoarthritis After Surgical or Nonsurgical Treatment of Anterior Cruciate Ligament Rupture: A Systematic Review.

OBJECTIVE: To determine if surgical or nonsurgical treatment of anterior cruciate ligament rupture affects the prevalence of posttraumatic tibiofemoral osteoarthritis (OA). DATA SOURCES: Studies published between 1983 and April 2012 were identified via EBSCOhost and OVID. Reference lists were then screened in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. STUDY SELECTION: Studies were included if (a) treatment outcomes focused on a direct comparison of surgical versus nonsurgical treatment of anterior cruciate ligament rupture, (b) the prevalence of tibiofemoral OA was reported, and (c) they were written in English. Studies were excluded if (a) the included patients were treated with cast immobilization after surgery, (b) the mean follow-up was less than 10 years, or (c) the patients underwent anterior cruciate ligament revision surgery. DATA EXTRACTION: Two independent investigators reviewed the included articles using the Newcastle-Ottawa Scale. Frequency of OA, surgical procedure, nonsurgical treatments, and participant characteristics were extracted and summarized. We calculated prevalence (%) and 95% confidence intervals for treatment groups for each individual study and overall. We developed 2 × 2 contingency tables to assess the association between treatment groups (exposed had surgery, referent was nonsurgical treatment) and the prevalence of OA. DATA SYNTHESIS: Four retrospective studies were identified (140 surgical patients, 240 nonsurgical patients). The mean Newcastle-Ottawa Scale score was 5 (range = 4-6 [of 10] points). Average length of follow-up was 11.8 years (range = 10-14 years). The prevalence of OA for surgically treated patients ranged from 32.6% to 51.2% (overall = 41.4%, 95% confidence interval = 35.0%, 48.1%) and for nonsurgical patients ranged from 24.5% to 42.3% (overall = 30.9%, 95% confidence interval = 24.4%, 38.3%). CONCLUSIONS: Although OA prevalence was higher in the surgical treatment group at a mean follow-up of 11.8 years, no definitive evidence supports surgical or nonsurgical treatment after anterior cruciate ligament injury to prevent posttraumatic OA. Current studies have been limited by small sample sizes, low methodologic quality, and a lack of data regarding confounding factors.

Is Participation in Certain Sports Associated With Knee Osteoarthritis? A Systematic Review.

OBJECTIVE: Information regarding the relative risks of developing knee osteoarthritis (OA) as a result of sport participation is critical for shaping public health messages and for informing knee-OA prevention strategies. The purpose of this systematic review was to investigate the association between participation in specific sports and knee OA. DATA SOURCES: We completed a systematic literature search in September 2012 using 6 bibliographic databases (PubMed; Ovid MEDLINE; Journals@Ovid; American College of Physicians Journal Club; Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Review, Database of Abstracts of Reviews of Effects; and Ovid HealthStar), manual searches (4 journals), and reference lists (56 articles). STUDY SELECTION: Studies were included if they met the following 4 criteria: (1) an aim was to investigate an association between sport participation and knee OA; (2) the outcome measure was radiographic knee OA, clinical knee OA, total knee replacement, self-reported diagnosis of knee OA, or placement on a waiting list for a total knee replacement; (3) the study design was case control or cohort; and (4) the study was written in English. Articles were excluded if the study population had an underlying condition other than knee OA. DATA EXTRACTION: One investigator extracted data (eg, group descriptions, knee OA prevalence, source of nonexposed controls). DATA SYNTHESIS: The overall knee-OA prevalence in sport participants (n = 3759) was 7.7%, compared with 7.3% among nonexposed controls (referent group n = 4730, odds ratio [OR] = 1.1). Specific sports with a significantly higher prevalence of knee OA were soccer (OR = 3.5), elite-level long-distance running (OR = 3.3), competitive weight lifting (OR = 6.9), and wrestling (OR = 3.8). Elite-sport (soccer or orienteering) and nonelite-sport (soccer or American football) participants without a history of knee injury had a greater prevalence of knee OA than nonexposed participants. CONCLUSIONS: Participants in soccer (elite and nonelite), elite-level long-distance running, competitive weight lifting, and wrestling had an increased prevalence of knee OA and should be targeted for risk-reduction strategies.

Physical activity levels and quality of life relate to collagen turnover and inflammation changes after running.

The purpose of this study was to determine whether an association existed between self-reported symptom and function scores and tissue turnover or inflammatory biomarker changes after a running bout among individuals with and without an acute knee-injury history. A pre-test/post-test prospective cohort study design (Level II) of 22 participants was conducted. Eleven physically active individuals with a history of anterior cruciate ligament surgery and/or meniscus surgery within 4 years of study participation were matched to 11 healthy control participants. All participants completed self-reported outcome measures (Knee Osteoarthritis Outcomes Score and Tegner activity level) assessing knee symptoms and functional levels prior to the run. Blood samples were taken both pre- and post-30-minute run at a prescribed pace on a treadmill to determine serum biomarker concentration changes. Tegner activity levels were inversely related to type II collagen/type II collagen synthesis marker ratio biomarker changes after the run (r = -0.45, p = 0.01). Quality-of-life scores pre-exercise were inversely related to interleukin-1ß changes after the run (r = -0.50, p = 0.02). No other correlation coefficients were statistically significant (r = -0.39 to 0.36). Ultimately, individuals with lower activity and quality-of-life scores experienced greater increases in collagen turnover and inflammation after a running bout, respectively. A gradual increase in activity (e.g., frequency, duration, intensity) may be warranted in this group prior to returning to activities that involve running. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:612-617, 2017.

Biochemical Response to a Moderate Running Bout in Participants With or Without a History of Acute Knee Injury.

CONTEXT: Individuals with an acute knee-injury history are 4 times more likely to develop knee osteoarthritis than those without a prior knee injury, and it is unknown why. Individuals with an injury history may exhibit aberrant changes in tissue turnover after physical activity (eg, running), which could lead to osteoarthritis, but this has yet to be determined among young, physically active individuals. OBJECTIVE: To determine collagen degradation and synthesis and inflammatory biomarker concentration levels before exercise and changes in response to an acute running bout in injured participants compared with healthy control participants. DESIGN: Cohort study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 22 physically active individuals between 18 and 25 years of age were recruited for the study: 11 injured participants (knee injury within 4 years of the study) who were medically cleared for physical activity and 11 matched healthy control participants. MAIN OUTCOME MEASURE(S): The independent variable was group (injured or control). Dependent variables were serum biomarker concentrations for cartilage oligomeric matrix protein, matrix metalloproteinase-13, proinflammatory marker interleukin-1ß, c-terminal cross-linking telopeptide of type II collagen, and type II collagen synthesis marker. Each participant provided prerun and postrun blood samples for biomarker-concentration analysis. RESULTS: No group differences existed in serum biomarker concentrations before exercise or in serum biomarker changes from pre-exercise to postexercise. CONCLUSIONS: After an acute bout of moderate-intensity running, young, active individuals in a high-risk postinjury population had similar biochemical responses as matched healthy controls. However, the external generalizability of these findings to other exercises and populations has yet to be determined.

Five-year clinical outcomes of a randomized trial of anterior cruciate ligament treatment strategies: an evidence-based practice paper.

REFERENCE/CITATION: Frobell RB, Roos HP, Roos EM, Roemer FW, Ranstam J, Lohmander LS. Treatment for acute anterior cruciate ligament tear: five year outcome of randomised trial. BMJ. 2013;346:F232. CLINICAL QUESTION: Does early anterior cruciate ligament (ACL) reconstruction with rehabilitation lead to better patient-reported outcomes and a lower incidence of osteoarthritis at 5 years postinjury compared with delayed ACL reconstruction with rehabilitation? STUDY SELECTION: This randomized controlled trial with extended follow-up at 5 years postrandomization was conducted in 2 Swedish orthopaedic departments. DATA EXTRACTION: The authors studied a total of 121 moderately active adults (age = 18-35 years) with an acute ACL rupture in a knee with no other history of trauma. Excluded were patients with a collateral ligament rupture, full-thickness cartilage defect, or extensive meniscal fixation. One patient assigned to the early ACL-reconstruction group did not attend the 5-year follow-up visit. Patients were randomly assigned to (1) an early ACL reconstruction plus structured rehabilitation group (n = 62, surgery within 10 weeks of injury) or (2) optional-delayed ACL reconstruction plus structured rehabilitation group (n = 59). The primary outcome measure was change in the average of 4 out of 5 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS). The authors also assessed crude KOOS (combined 4 subscales), KOOS subscale scores, general physical and mental health (Short-Form 36), activity level (Tegner Activity Scale), mechanical knee stability (Lachman and pivot shift tests), meniscal surgery status, and presence of knee osteoarthritis on radiographs. MAIN RESULTS: Among patients randomized to the optional-delayed ACL-reconstruction group, 30 (51%) opted for an ACL reconstruction. The treatment groups had comparable 5-year patient-reported outcomes and changes in patient-reported outcomes (eg, knee pain, knee symptoms, activities of daily living, sport and recreational levels, knee-related quality of life, general physical health, and general mental health). Patients in the optional-delayed ACL-reconstruction group had greater mechanical knee instability than patients who received early ACL reconstruction; however, this was primarily among the patients opting for conservative management alone. In the overall sample, 61 knees (51%) required meniscal surgery over 5 years, regardless of treatment group. At 5 years, radiographs were available for 113 patients (93%). Overall, 29 patients (26%) had knee osteoarthritis at 5 years. Specifically, 13 patients (12%) developed tibiofemoral radiographic osteoarthritis (9 patients [16%] in the early ACL-reconstruction group, 4 [7%] in the optional-delayed ACL-reconstruction group) and 22 (19%) developed patellofemoral osteoarthritis (14 patients [24%] in the early ACL-reconstruction group, 8 [15%] in the optional-delayed ACL-reconstruction group). Patients with patellar tendon grafts (n = 40) had a greater incidence of ipsilateral patellofemoral osteoarthritis than patients with hamstrings tendon grafts (n = 51), but the 2 groups had similar incidences of ipsilateral tibiofemoral osteoarthritis. Six knees (5%) had both tibiofemoral and patellofemoral osteoarthritis. CONCLUSIONS: Early ACL reconstruction plus rehabilitation did not provide better results at 5 years compared with optional-delayed ACL reconstruction plus rehabilitation. Furthermore, the authors found no radiographic differences among patients with early ACL reconstruction, delayed ACL reconstruction, or no ACL reconstruction (rehabilitation alone).

Saline-assisted aspirations for collecting synovial fluid from noneffused knees: technique and validation.

CONTEXT: To better understand why a knee develops osteoarthritis after joint trauma we need to assess the local biochemical changes. Unfortunately, it is challenging to obtain synovial fluid from a knee with no effusion. OBJECTIVE: To describe the authors' protocol for aspirating synovial fluid from noneffused knees. Second, they demonstrate the validity of this method by evaluating the relationships between normalized and raw biomarker concentrations among knees with effusion (undergoing a traditional aspiration) and without effusion (requiring a saline-assisted aspiration). DESIGN: Validation study based on secondary analyses from 2 cohort studies. SETTING: Outpatient orthopedic clinic and basic-science laboratory. PARTICIPANTS: Participants had moderate to severe radiographic knee osteoarthritis (n = 15 with and 11 without effusion) and no osteoarthritis or effusion (n = 4). INTERVENTIONS: The same orthopedic surgeon performed all synovial-fluid joint aspirations, including saline-assisted aspirations. MAIN OUTCOME MEASURES: The authors used multiplex enzyme-linked immunosorbent assays to determine 7 synovial-fluid biomarker concentrations. They then calculated correlations between raw and normalized (to total synovial-fluid protein content) biomarker concentrations. RESULTS: The authors excluded 1 sample collected with a saline-assisted aspiration because it contained blood. Normalized biomarker concentrations had positive associations with raw biomarker concentrations (r = .77-.99), with the exception of interleukin-13 and interleukin-1ß among knees that underwent a saline-assisted aspiration. Excluding interleukin-1ß, associations between normalized and raw biomarker concentrations were consistent between knees that had a saline-assisted or traditional aspiration. CONCLUSIONS: Saline-assisted aspiration is a valid technique for assessing the local biochemical changes in knees without effusion.

Medication and supplement use for managing joint symptoms among patients with knee and hip osteoarthritis: a cross-sectional study.

BACKGROUND: The purpose was to determine the professionally-guided and self-guided medication and supplement use for joint symptom management among patients with knee and/or hip osteoarthritis (OA) in an urban hospital-based outpatient orthopedic practice. METHODS: The study design was cross-sectional. Patients diagnosed by radiographs and clinical symptoms with knee and/or hip OA were recruited from an inner-city hospital-based outpatient orthopaedic office. A total of 184 patients were queried for their participation. Four investigator-generated, interview-based questionnaires were used. Sampling error was ±7.84%. Logistic regression models and Fisher Exact Tests were performed to determine factors that may be associated with negative behaviors related to medication or supplement use (e.g., reporting medication as ineffective, using multiple medications in the same day to manage symptoms). Odds ratios (OR) and 95% confidence intervals (CI) were calculated for significant findings. RESULTS: Among the 162 participants, a majority reported professionally-guided recommendations and over 40% reported at least one self-guided intervention. 37 participants reported dual-use during the same day, and among those,15 reported dual-use at the same time. Among participants taking multiple interventions in the same day, 40.5% reported using prescription and over-the-counter medications. Use of multiple medications or supplements in one day was more common among participants who reported OA at multiple joints (OR [95% CI]=2.48 [1.03 to 5.96]) but less common among participants who did not complete high school (OR [95% CI]=0.26 [0.08 to 0.83]). Of the 15 participants who reported dual-use at the same time, 11 were professionally-guided, 5 were professional and self-guided, and 1 was solely self-guided. Overall, 28% of participants reported their intervention as ineffective, sought an alternative method to achieve symptomatic relief, or were prescribed a stronger medication. Participants who reported not always taking their medication consistently for 2 weeks were more likely to report their medication as ineffective (OR [95% CI]=2.87 [1.19 to 6.92]). CONCLUSIONS: Both professional and self-guided medications and supplements are used by inner city OA patients to manage their joint symptoms. It is important for clinicians to discuss with these patients how to effectively manage multiple joint symptoms, the importance of taking medications as prescribed, and what they should if they believe a treatment is ineffective or their medication runs out.

Consequences of pediatric obesity on the foot and ankle complex.

BACKGROUND: Anthropometric status can influence gait biomechanics, but there is relatively little published research regarding foot and ankle characteristics in the obese pediatric population. We sought to compare the structural and functional characteristics of the foot and ankle complex in obese and non-obese children. METHODS: Twenty healthy children (ten obese and ten normal weight) were recruited for a cross-sectional research study. Anthropometric parameters were measured to evaluate active ankle dorsiflexion, arch height (arch height index, arch rigidity index ratio, and arch drop), foot alignment (resting calcaneal stance position and forefoot-rearfoot alignment in unloaded and loaded positions), and foot type (malleolar valgus index). Independent t tests determined significant differences between groups for all assessed parameters. Statistical significance was set at P < .0125. RESULTS: Compared with non-obese participants, obese participants had significantly greater arch drop (mean ± SD: 5.10 ± 2.13 mm versus 2.90 ± 1.20 mm; P =.011) and a trend toward lower arch rigidity index ratios (mean ± SD: 0.92 ± 0.03 versus 0.95 ± 0.02; P = .013). In addition, obese participants had significantly less active ankle dorsiflexion at 90° of knee flexion versus non-obese participants (mean ± SD: 19.57 ± 5.17 versus 29.07 ± 3.06; P < .001). No significant differences existed between groups for any other anthropometric measurements. CONCLUSIONS: The decreased active ankle dorsiflexion in the obese group can increase foot contact for a longer period of the stance phase of gait. Obese participants also presented with a more flexible foot when bearing weight.

Biochemical comparison of osteoarthritic knees with and without effusion.

BACKGROUND: Several symptom-relieving interventions have been shown to be efficacious among osteoarthritis (OA) patients with knee effusion; however, not every symptomatic knee OA patient has clinical effusion. Results may be over-generalized since it is unclear if effused knees represent a unique pathological condition or subset compared to knees without effusion. The primary purpose of this study was to determine if biochemical differences existed between OA knees with and without effusion. METHODS: The present cross-sectional study consisted of 22 volunteers (11 with knee effusion, 11 without knee effusion) with confirmed late-stage radiographic knee OA (Kellgren-Lawrence score ≥ 3). Synovial fluid samples were collected and analyzed using a custom multiplex enzyme-linked immunosorbent assay to determine eight specific biomarker concentrations (e.g., catabolic, anabolic). RESULTS: Matrix metalloproteinase (MMP)-3, tissue inhibitor of MMPs (TIMP)-1, TIMP-2, and interleukin-10 were significantly higher in the knees with effusion than in the knees without effusion. CONCLUSIONS: The biochemical differences that existed between knees with and without effusion provide support that OA subsets may exist, characterized by distinct biochemical characteristics and clinical findings (e.g., effusion).

Joint inflammation and early degeneration induced by high-force reaching are attenuated by ibuprofen in an animal model of work-related musculoskeletal disorder.

We used our voluntary rat model of reaching and grasping to study the effect of performing a high-repetition and high-force (HRHF) task for 12 weeks on wrist joints. We also studied the effectiveness of ibuprofen, administered in the last 8 weeks, in attenuating HRHF-induced changes in these joints. With HRHF task performance, ED1+ and COX2+ cells were present in subchondral radius, carpal bones and synovium; IL-1alpha and TNF-alpha increased in distal radius/ulna/carpal bones; chondrocytes stained with Terminal deoxynucleotidyl Transferase- (TDT-) mediated dUTP-biotin nick end-labeling (TUNEL) increased in wrist articular cartilages; superficial structural changes (e.g., pannus) and reduced proteoglycan staining were observed in wrist articular cartilages. These changes were not present in normal controls or ibuprofen treated rats, although IL-1alpha was increased in reach limbs of trained controls. HRHF-induced increases in serum C1,2C (a biomarker of collagen I and II degradation), and the ratio of collagen degradation to synthesis (C1,2C/CPII; the latter a biomarker of collage type II synthesis) were also attenuated by ibuprofen. Thus, ibuprofen treatment was effective in attenuating HRHF-induced inflammation and early articular cartilage degeneration.

Reliability and validity of three quality rating instruments for systematic reviews of observational studies.

To assess the inter-rater reliability, validity, and inter-instrument agreement of the three quality rating instruments for observational studies. Inter-rater reliability, criterion validity, and inter-instrument reliability were assessed for three quality rating scales, the Downs and Black (D&B), Newcastle-Ottawa (NOS), and Scottish Intercollegiate Guidelines Network (SIGN), using a sample of 23 observational studies of musculoskeletal health outcomes. Inter-rater reliability for the D&B (Intraclass correlations [ICC] = 0.73; CI = 0.47-0.88) and NOS (ICC = 0.52; CI = 0.14-0.76) were moderate to good and was poor for the SIGN (κ = 0.09; CI = -0.22-0.40). The NOS was not statistically valid (p = 0.35), although the SIGN was statistically valid (p < 0.05) with medium to large effect sizes (f(2) = 0.29-0.47). Inter-instrument agreement estimates were κ = 0.34, CI = 0.05-0.62 (D&B versus SIGN), κ = 0.26, CI = 0.00-0.52 (SIGN versus NOS), and κ = 0.43, CI = 0.09-0.78 (D&B versus NOS). Reliability and validity are quite variable across quality rating scales used in assessing observational studies in systematic reviews. Copyright © 2011 John Wiley & Sons, Ltd.

The potential of multiple synovial-fluid protein-concentration analyses in the assessment of knee osteoarthritis.

CONTEXT: Joint trauma is a risk factor for osteoarthritis (OA), which is becoming an increasingly important orthopedic concern for athletes and nonathletes alike. For advances in OA prevention, diagnosis, and treatment to occur, a greater understanding of the biochemical environment of the affected joint is needed. OBJECTIVE: To demonstrate the potential of a biochemical technique to enhance our understanding of and diagnostic capabilities for osteoarthritis. DESIGN: Cross-sectional. SETTING: Outpatient orthopedic practice. PARTICIPANTS: 8 subjects: 4 OA-knee participants (65 ± 6 y of age) and 4 normal-knee participants (54 ± 10 y) with no history of knee OA based on bilateral standing radiographs. INTERVENTION: The independent variable was group (OA knee, normal knee). MAIN OUTCOME MEASURES: 16 knee synovial-protein concentrations categorized as follows: 4 as pro-inflammatory, or catabolic, cytokines; 5 as anti-inflammatory, or protective, cytokines; 3 as catabolic enzymes; 2 as tissue inhibitors of metalloproteinases [TIMPs]; and 2 as adipokines. RESULTS: Two anti-inflammatory cytokines (interleukin [IL]-13 and osteoprotegerin) and a pro-inflammatory cytokine (IL-1ß) were significantly lower in the OA knees. Two catabolic enzymes (matrix metalloproteinase [MMP]-2 and MMP-3) were significantly elevated in OA knees. TIMP-2, an inhibitor of MMPs, was significantly elevated in OA knees. CONCLUSIONS: Six of the 16 synovial-fluid proteins were significantly different between OA knees and normal knees in this study. Future research using a similar multiplex ELISA approach or other proteomic techniques may enable researchers and clinicians to develop more accurate biochemical profiles of synovial fluid to help diagnose OA, identify subsets of OA or individual characteristics, guide clinical decisions, and identify patients at risk for OA after knee injury.

Body size and walking cadence affect lower extremity joint power in children's gait.

Obese children move less and with greater difficulty than normal-weight counterparts but expend comparable energy. Increased metabolic costs have been attributed to poor biomechanics but few studies have investigated the influence of obesity on mechanical demands of gait. This study sought to assess three-dimensional lower extremity joint powers in two walking cadences in 28 obese and normal-weight children. 3D-motion analysis was conducted for five trials of barefoot walking at self-selected and 30% greater than self-selected cadences. Mechanical power was calculated at the hip, knee, and ankle in sagittal, frontal and transverse planes. Significant group differences were seen for all power phases in the sagittal plane, hip and knee power at weight acceptance and hip power at propulsion in the frontal plane, and knee power during mid-stance in the transverse plane. After adjusting for body weight, group differences existed in hip and knee power phases at weight acceptance in sagittal and frontal planes, respectively. Differences in cadence existed for all hip joint powers in the sagittal plane and frontal plane hip power at propulsion. Frontal plane knee power at weight acceptance and sagittal plane knee power at propulsion were significantly different between cadences. Larger joint powers in obese children contribute to difficulty performing locomotor tasks, potentially decreasing motivation to exercise.

Is osteoarthritis a heterogeneous disease that can be stratified into subsets?

Osteoarthritis is a heterogeneous disease characterized by variable clinical features, biochemical/genetic characteristics, and responses to treatments. To optimize palliative effects of current treatments and develop efficacious disease-modifying interventions, treatments may need to be tailored to the individual or a subset of osteoarthritic joints. The purpose of this review is to explore the current literature on the clinical and physiological variability in osteoarthritis and potential for stratifying patients. Several stratifications have been reported, including mechanism of onset, stage of disease progression, involved joints, inflammatory levels, and effusion. Most of these methods revealed two to three unique subsets of osteoarthritis. Osteoarthritic joints may be stratified by an array of variables, some transient and others consistent throughout the disease process. Future research needs to continue to explore stratification techniques since these may be the key to optimizing palliative interventions and developing disease-modifying interventions for subsets within this heterogeneous disease.

Effects of pediatric obesity on joint kinematics and kinetics during 2 walking cadences.

UNLABELLED: Shultz SP, Sitler MR, Tierney RT, Hillstrom HJ, Song J. Effects of pediatric obesity on joint kinematics and kinetics during 2 walking cadences. OBJECTIVE: To determine whether differences existed in lower-extremity joint biomechanics during self-selected walking cadence (SW) and fast walking cadence (FW) in overweight- and normal-weight children. DESIGN: Survey. SETTING: Institutional gait study center. PARTICIPANTS: Participants (N=20; mean age +/- SD, 10.4+/-1.6y) from referred and volunteer samples were classified based on body mass index percentiles and stratified by age and sex. Exclusion criteria were a history of diabetes, neuromuscular disorder, or recent lower-extremity injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sagittal, frontal, and transverse plane angular displacements (degrees) and peak moments (newton meters) at the hip, knee, and ankle joints. RESULTS: The level of significance was set at P less than .008. Compared with normal-weight children, overweight children had greater absolute peak joint moments at the hip (flexor, extensor, abductor, external rotator), the knee (flexor, extensor, abductor, adductor, internal rotator), and the ankle (plantarflexor, inverter, external/internal rotators). After including body weight as a covariate, overweight children had greater peak ankle dorsiflexor moments than normal-weight children. No kinematic differences existed between groups. Greater peak hip extensor moments and less peak ankle inverter moments occurred during FW than SW. There was greater angular displacement during hip flexion as well as less angular displacement at the hip (extension, abduction), knee (flexion, extension), and ankle (plantarflexion, inversion) during FW than SW. CONCLUSIONS: Overweight children experienced increased joint moments, which can have long-term orthopedic implications and suggest a need for more nonweight-bearing activities within exercise prescription. The percent of increase in joint moments from SW to FW was not different for overweight and normal-weight children. These findings can be used in developing an exercise prescription that must involve weight-bearing activity.

Stiffness regulation and muscle-recruitment strategies of the shoulder in response to external rotation perturbations.

BACKGROUND: The complex interactions between capsuloligamentous structures and muscle-recruitment strategies that maintain glenohumeral stability remain unclear. The purposes of the present study were to determine whether stiffness regulation and muscle-activation strategies differed under varying joint positions and levels of contraction in the shoulder and to determine the relationship between generalized joint laxity, glenohumeral joint laxity, and joint stiffness. METHODS: Forty healthy, physically active subjects with a mean age (and standard deviation) of 25.2 +/- 4.6 years, a mean height of 174.7 +/- 6.7 cm, and a mean mass of 73.1 +/- 13.8 kg were tested. Shoulder stiffness and the activation of muscles (including the rotator cuff and the anterior deltoid) were measured at two levels of internal rotation torque (0% and 50% of maximum) and two joint positions (0 degrees and 90% of maximum external rotation) before and after a 5 degrees external rotation perturbation. Generalized laxity and glenohumeral joint laxity (in the anterior, posterior, and inferior directions) were also assessed. RESULTS: Stiffness was 77% greater at 50% of maximum internal rotation torque than at 0% of maximum internal rotation torque (p < 0.001) but was not significantly different between joint positions (p = 0.73). From 0% to 50% of maximum internal rotation torque, preparatory and reactive recruitment of the subscapularis increased significantly more (p < 0.05) than those of the other muscles. Also, subscapularis preparatory activity was 36% greater in 0 degrees of external rotation than in 90% of maximum external rotation (p < 0.01). Generalized joint laxity (as indicated by a score of >/=4) was present in 20% of the subjects. Glenohumeral joint laxity (as indicated by a grade of >/=2) was present in the anterior, posterior, and inferior directions in 13%, 15%, and 15% of the subjects, respectively. No correlation existed between passive stiffness and generalized or glenohumeral laxity (r = -0.12 to 0.29; p = 0.08 to 0.48). CONCLUSIONS: Moderate levels of muscle contraction can significantly increase glenohumeral joint stiffness and stability. Preactivation of the subscapularis appears to be the primary dynamic stabilizer with the arm in 0 degrees of external rotation. However, with the arm in 90% of maximum external rotation (the apprehension position), less subscapularis activity is observed and the maintenance of stability may shift toward other musculoskeletal structures because joint stiffness does not change. A relationship between generalized joint laxity, glenohumeral laxity, and stiffness was not observed in healthy subjects.

Dehydration and symptoms of delayed-onset muscle soreness in normothermic men.

CONTEXT: A dehydrated individual who performs eccentric exercise may exacerbate skeletal muscle damage, leading to structural, contractile, and enzymatic protein denaturation, in addition to the myofiber and connective damage resulting from the eccentric muscle tension. OBJECTIVE: To identify the effects of dehydration on 5 physiologic characteristics of delayed-onset muscle soreness (DOMS) in normothermic men after an eccentric exercise perturbation. DESIGN: Randomized group test-retest design. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten healthy male volunteers randomly assigned to either a euhydration (age = 26.2 +/- 4.9 years, height = 174.1 +/- 6.0 cm, mass = 86.5 +/- 15.3 kg) or dehydration (age = 25.8 +/- 2.2 years, height = 177.2 +/- 3.1 cm, mass = 84.4 +/- 3.8 kg) group. INTERVENTION(S): Subjects performed treadmill walking for 45 minutes in either a thermoneutral (euhydration) or a hot, humid (dehydration) environment. After a rest period to allow for return to the normothermic condition, DOMS was induced with a 45-minute downhill run. MAIN OUTCOME MEASURES: We assessed 5 physiologic characteristics of DOMS before and at intervals after the eccentric exercise. The characteristics were perceived pain of the bilateral quadriceps and overall body, bilateral punctate tenderness of the superficial quadriceps muscles, bilateral knee-flexion passive range of motion, bilateral thigh circumference, and bilateral isometric quadriceps muscle strength. Thermoregulatory and cardiovascular measures were obtained to monitor participants' heat load during exercise. RESULTS: The experimental protocol produced a 0.9% increase in body mass of the euhydration group and a significant 2.7% decrease in body mass of the dehydration group. The downhill-running exercise perturbation induced DOMS in both the euhydrated and dehydrated participants, based on increased bilateral quadriceps and overall body perceived pain and punctate tenderness of the bilateral vastus medialis muscle. The signs and symptoms of DOMS after an eccentric exercise perturbation were not exacerbated by moderate dehydration of 2.7% body mass after rest and return to the normothermic condition. CONCLUSIONS: Significantly dehydrated participants who rested and returned to a normothermic condition did not experience increased characteristics of DOMS.