Osteoarthritis Participants Research Articles

Inflammatory biomarkers, endogenous analgesia and gait characteristics in those with moderate medial compartment knee osteoarthritis who experience increased pain after 30 minutes of continuous walking

Purpose: Walking is recommended for those with knee osteoarthritis (OA) to improve pain; however, numerous reports of increased pain after walking exist following short durations of activity. The purpose of this study was to quantify the concurrent response of inflammatory biomarkers, endogenous analgesia and gait biomechanics to 30 minutes of physical activity across individuals with varied pain responses. The hypothesis was that those with medial compartment knee OA who self-reported an increase in pain following a 30-min walk would have a greater increase in inflammatory biomarkers, less increase in endogenous analgesia and a gait pattern consistent with a higher risk of clinical progression based on knee adduction moment (KAM) magnitude and dynamic knee flexion moment (KFM) unloading features compared to OA participants with no increase in pain and asymptomatic controls (ASYM).

Comparison of gait, functional activities, and patient-reported outcome measures in patients with knee osteoarthritis and healthy adults using 3D motion analysis and activity monitoring: an exploratory case-control analysis.

ObjectiveTo examine functional performance differences using kinematic and kinetic analysis between participants with and without knee osteoarthritis (OA) to determine which outcomes best characterize persons with and without knee OA.MethodsParticipants with unilateral moderate knee OA (Kellgren–Lawrence grades 2 or 3) and controls without knee pain were matched for age, gender, and body mass index. Primary outcomes included temporal parameters, joint rotations and moments, and ground reaction forces assessed via 3D motion capture during walking and ascending/descending stairs. Secondary outcomes included timed functional activities (sit to stand; tying shoelaces), 48 hrs lower limb activity monitoring, and patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, European Quality of Life–5 Dimensions).ResultsEight matched pairs were analyzed. Compared with controls, OA participants exhibited significant reductions in peak frontal hip and sagittal knee moments, and decreased peak anterior ground reaction force with the affected limb while walking. Ascending stairs, OA participants had slower speed, fewer strides per minute, longer cycle and stance times, and increased trunk range of motion (ROM) in assessments of both limbs; longer swing time and reduced ankle ROM in the affected limb; and increased knee frontal ROM in the unaffected limb. Descending stairs, OA participants had fewer strides per minute and decreased trunk transverse ROM in assessments of both limbs; increased knee frontal ROM in the affected limb; and longer strides, shorter stance and cycle times, increased trunk sagittal and decreased knee transverse ROMs in the unaffected limbs vs controls. Compared with controls, OA participants had slower walking cadence (120–130 vs 100–110 steps/min, respectively), took significantly longer on timed functional measures, and had significantly worse scores in patient-reported outcomes.ConclusionSeveral objectives and patient-reported measures examined in this study could potentially be considered as outcomes in pharmacologic or physical therapy OA trials.

The Validity, Reliability, Measurement Error, and Minimum Detectable Change of the 30-Second Fast-Paced Walk Test in Persons with Knee Osteoarthritis: A Novel Test of Short-Distance Walking Ability.

ObjectiveTo develop and establish the reliability, validity, measurement error, and minimum detectable change of a novel 30‐second fast‐paced walk test (30SFW) in persons with knee osteoarthritis (OA) that is easy to administer and can quantify walking performance in persons of all abilities.MethodsTwenty females with symptomatic knee OA (mean age [SD] 58.30 [8.05] years) and 20 age‐ and sex‐matched asymptomatic controls (57.25 [8.71] years) participated in the study. Participants completed questionnaires of demographic and clinical data, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 36‐item Short Form Health Survey (SF‐36) followed by 30SFW performance. Participants returned 2‐7 days later and performed the 30SFW again.ResultsThe knee OA group reported function that was worse than controls (all KOOS subscales; P < 0.0001). The 30SFW intrarater and interrater reliability were excellent [ICC (2,1) = 0.95‐0.99]. Knee OA participants walked a shorter distance in the 30SFW than controls (mean [SD]: OA 44.4 m [9.5 m]; control 58.1 m [7.8 m]; P < 0.0001). Positive strong correlations were found between the 30SFW and the KOOS–Activity of Daily Living, SF‐36‐Physical Functioning, and SF‐36‐Physical Health Composite scores (P < 0.0001). A nonsignificant, weak correlation between 30SFW and SF‐36‐Mental Health scores was present (r = 0.32, P = 0.05).ConclusionThe 30SFW has excellent intrarater and interrater reliability. The 30SFW demonstrated excellent known groups, convergent, and discriminant validity as a measure of short‐distance walking ability in persons with knee OA. Clinicians and researchers should consider using the 30SFW to quantify walking ability in persons with knee OA and assess walking ability change.

Influence of metabolic syndrome on thigh intermuscular fat in older adults with knee osteoarthritis

Influence of metabolic syndrome on thigh intermuscular fat in older adults with knee osteoarthritis

Association of bone marrow lesions localisation with weight bearing pain in people with knee osteoarthritis: data from the osteoarthritis initiative

Purpose: Subchondral bone contributes to pain in knee osteoarthritis (OA). OA structural change particularly affects weight-bearing components of the joint, most notably the medial femorotibial compartment in people with varus angulation. Subchondral bone marrow lesions (BMLs) detected on MRI in knee OA are strongly associated with pain. BMLs typically occur in regions of the joint with the most severe structural change, for example, full-thickness cartilage lesions. However, the association between subchondral BMLs in weight-bearing components and weight-bearing pain has not been clarified. The purpose of this study was to assess association between BMLs location and weight bearing knee pain using data from the Osteoarthritis Initiative (OAI). We hypothesized that BMLs at the medial femorotibial joint compartment were associated with weight bearing pain, independent of non-weight bearing pain, and that changes in size of the BMLs over time were associated with change in weight bearing pain. Methods: The OAI is a publicly available multi-center, longitudinal, prospective observational study of knee OA. We examined the knees of OAI participants with MRI readings using the MRI Osteoarthritis Knee Score (MOAKS). BMLs, articular cartilage, osteophytes, Hoffa’s synovitis, effusion, meniscal morphology and anterior cruciate ligament tears were scored using the MOAKS, and femorotibial angle (FTA) and Body Mass Index (BMI) were examined. BML scores using MOAKS were available for 4 articular sub-regions (median and lateral femorotibial, and medial and lateral patellofemoral joint) and the subspinous region. Knee pain was assessed at baseline (cross-sectional) and baseline and 2 years (longitudinal) using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We defined weight bearing pain as the sum of three WOMAC questions (pain on climbing stairs, on walking, and on standing) and non-weight bearing pain as the sum of two WOMAC questions (pain in bed and with sitting/lying down). Negative binomial regression was performed, using SPSS version 23 software. Results: 1412 participants were included in the cross-sectional analysis (from OAI project 22, 30 and 65), mean age 62 (±9) years, mean BMI 30 (±5), 61% female, median weight and non-weight bearing WOMAC score 2 (IQR 0, 4) and 0 (IQR 0, 1), and median total BML score 3 (IQR 1, 6). Weight bearing pain was associated with total BML score was r = 0.35 (p < 0.0001), and with BML scores at medial (r=0.29, p < 0.0001) and lateral (r=0.09, p = 0.0009) femorotibial joint compartments. Weight bearing pain was also associated with BML score at medial and lateral patellofemoral joint compartments (r = 0.03, p = 0.3 and 0.13, p < 0.0001, respectively). The association between weight bearing pain and BML scores at medial femorotibial and lateral patellofemoral joint compartments remained significant after adjusting for non-weight bearing pain, age, sex, BMI, FTA, BML scores at the other 4 joint compartments and the other OA related MRI features (osteophyte score, cartilage defect score, medial meniscus extrusion, anterior cruciate ligament tears, synovitis and effusion) (Table 1). 600 participants were included in the longitudinal study (OAI project 22), mean age 62 (± 9) years, mean BMI 31 (± 5), 57% female, median weight and non-weight bearing WOMAC score 1 (IQR 0, 3) and 0 (IQR 0, 1), and median total BML score 3 (IQR 2, 5). From baseline to 2 years, the changes in the mean weight and non-weight bearing 0.5 (±2.2) and 0.1 (±1.4), and mean total BML score were 0.7 (±1.9). The correlation between changes in weight bearing pain and changes in total BML score was r = 0.13 (p = 0.002); between changes in weight-bearing pain and BML score at medial and lateral femorotibial joint compartment were r = 0.16 (p < 0.0001) and -0.03 (p = 0.45), between changes in weight-bearing pain and changes in BML score at medial and lateral patellofemoral joint compartment were r = 0.04 (p = 0.3) and -0.03 (p = 0.5). The association between the changes in BML score at medial femorotibial joint compartment and changes in weight-bearing pain remained significant after adjusting for changes in non-weight bearing pain, age, sex, BMI, BML change at the other four joint compartments and osteophyte score change (Table 2). Conclusions: In this cross sectional and longitudinal study, BMLs at medial femorotibial joint compartment in varus knee OA participants were highly associated with the severity and the change in severity of weight bearing pain. The associations persisted when mutually adjusting for other feature of OA related MRI features, and adjusting for non-weight bearing pain, age, sex and BMI. Our findings suggest that BMLs in weight-bearing areas might contribute to weight bearing pain. Reducing BMLs or weight bearing in joint compartments with BMLs are candidate treatment targets in knee OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Pressure algometry and palpation of the upper limb peripheral nervous system in subjects with hand osteoarthritis are repeatable and suggest central changes

Study DesignCase-control study. IntroductionA subset of patients with hand osteoarthritis (OA) shows evidence of central pain phenotypes. Purpose of the StudyTo examine whether differences exist in experimental pain responses in the affected and nonaffected sides of patients with unilateral hand OA. To investigate the test-retest reliability of pressure algometry and manual digital palpation in patients with unilateral hand OA. MethodsThe hand OA group consisted of 20 patients, and the control group consisted of 20 healthy subjects. Pressure pain threshold (PPT) measurements were made 2 times, consisting of 3 repeat trials, each using computerized algometry and manual digital palpation. Grip and key strength (dynamometer), pain (visual analog scale), and function (Disabilities of the Arm, Shoulder and Hand [short version]) were also measured. The 2-way analysis of variance was conducted to determine the differences between sides and groups. Intraclass correlation coefficient (ICC) and standard error of measurement were calculated. ResultsPatients with hand OA had decreased PPTs over the thumb carpometacarpal joint as well as radial and median nerves compared with controls (all P < .01). No significant group effect by side interaction was detected for any measure. The minimal detectable change values needed to detect change in subjects with hand OA were C5-C6 joint (0.3-0.5 kg/cm2), carpometacarpal joint (0.3-0.5 kg/cm2), hamate bone (0.2-0.4 kg/cm2), radial nerve (0.2-0.8 kg/cm2), median nerve (0.3-0.6 kg/cm2), and ulnar nerve (0.2-0.4 kg/cm2) for PPT. Test-retest reliability was calculated for both hands of participants with OA (ICC, 0.98-0.99) and healthy participants (ICC, 0.74-0.99). DiscussionAlthough pressure algometry and manual digital palpation are techniques already used in previous studies and have been shown to be reproducible and moderately reliable for joint palpation, this current study suggests that pressure algometry and manual digital palpation could also be reliable methods of determining nerve sensitivity of the radial, ulnar and median nerves in subjects with hand OA. ConclusionsHyperalgesia in patients with hand OA might be associated with clinical measures, and bilateral signs in unilateral OA could suggest central changes.

Somatosensation in OA: exploring the relationships of pain sensitization, vibratory perception and spontaneous pain

BackgroundPain in osteoarthritis (OA) remains poorly understood. Different types of somatosensory alterations exist in OA including hyperesthesia and increased sensitivity to painful stimuli as well as those of decreased sensitivity to cutaneous stimuli including vibratory perception threshold. The relationship between these different somatosensory measures has not been previously evaluated in OA. In this observational study, we evaluated relationships between vibratory perception (VPT), pressure pain detection thresholds (PPT), allodynia and subjective pain in knee OA.MethodsForty-two persons with moderate to severe knee OA and 12 controls without OA were evaluated. VPT was measured using a biothesiometer. Allodynia was measured by application of a 60 g Von Frey monofilament repeatedly to predetermined sites. PPTs were measured using a pressure algometer.ResultsIncreased vibratory acuity was associated with lower PPTs and presence of allodynia. Allodynia was more common in OA than controls (54.8% vs 16.6%, p = 0.024 in the ipsilateral knee, and 42.9% vs 0%, p = 0.005 in the contralateral knee). OA participants with allodynia had lower PPTs than those without allodynia. In those with OA, spontaneous knee pain was associated with lower PPTs and with allodynia.ConclusionThis study confirms the presence of somatosensory alterations in OA. Sensory alterations (vibratory perception) were shown to be related to nociceptive alterations (sensitization) in OA, showing a general increased sensitivity to cutaneous mechanical stimulation. Understanding these relationships is an important step in delineating the complicated pathophysiology of pain processing in OA.

Reduced anterior cingulate grey matter volume in painful hand osteoarthritis

ObjectiveIncreasing evidence supports the role of central sensitisation in osteoarthritis (OA) pain. In this study, we used neuroimaging to compare pain-processing regions of the brain in participants with and without hand OA. We then assessed for volumetric changes in these brain regions following treatment with centrally acting analgesics.MethodsParticipants with hand OA (n = 28) underwent T1-weighted MRI of the brain before and after 12 weeks of treatment with pregabalin, duloxetine or placebo. Grey matter volume in the anterior cingulate cortex (ACC), insular cortex and thalamus was compared to non-OA control subjects (n = 11) using FreeSurfer regional volumetric analysis and voxel-based morphometry, and evaluated for differences pre- and post-treatment.ResultsRelative to non-OA controls, hand OA participants had areas of reduced grey matter volume in the ACC at baseline (p = 0.007). Regional volumetric differences in the ACC persisted after 13 weeks’ treatment with pregabalin or duloxetine (p = 0.004) with no significant differences between treatment cohorts, despite improvements in NRS pain scores for pregabalin (p = 0.005) and duloxetine (p = 0.050). The ACC grey matter changes persisted despite a significant improvement in pain in the pregabalin and duloxetine groups vs. placebo. No structural differences were observed in the insular cortex or thalamus at baseline or following treatment.ConclusionOur study found evidence of reduced ACC grey matter volume in participants with hand arthritis that persisted after treatment with centrally acting analgesics pregabalin and duloxetine, respectively. The sustained changes observed in the ACC in our study could reflect the relatively short duration of treatment, or that the differences observed are irreversible volume changes due to chronic pain that are established over time.

A 6-week hip muscle strengthening and lumbopelvic-hip core stabilization program to improve pain, function, and quality of life in persons with patellofemoral osteoarthritis: a feasibility pilot study

BackgroundPatellofemoral joint (PFJ) osteoarthritis (OA) is prevalent in middle-aged and older adults. Despite this, there are minimal studies which have examined conservative interventions for PFJ OA. Weakness of proximal lower extremity muscles is associated with PFJ OA. It is unknown if a hip muscle strengthening and lumbopelvic-hip core stabilization program will improve symptoms and function in persons with PFJ OA. This study examined the feasibility and impact of a 6-week hip muscle strengthening and core stabilization program on pain, symptoms, physical performance, peak muscle torques, and quality of life in persons with PFJ OA.MethodsTen females with PFJ OA and ten age- and sex-matched controls participated in baseline tests. PFJ OA participants attended ten twice-a-week hip strengthening and core stabilization exercise sessions. Outcome measures included questionnaires, the Timed-Up-and-Go, and peak isometric torque of hip and quadriceps muscles. Data were tested for normality; parametric and non-parametric tests were used as appropriate.ResultsAt baseline, the PFJ OA group had significantly worse symptoms, slower Timed-Up-and-Go performance, and lower muscle torques than control participants. PFJ OA group adherence to supervised exercise sessions was adequate. All PFJ OA participants attended at least nine exercise sessions. Five PFJ OA participants returned 6-month follow-up questionnaires, which was considered fair retention. The PFJ OA participants’ self-reported pain, symptoms, function in daily living, function in sport, and quality of life all improved at 6 weeks (P < 0.05). Timed-Up-and-Go time score improved at 6 weeks (P = 0.005). Peak hip external rotator torque increased (P = 0.01). Improvements in pain and self-reported function were no longer significant 6 months following completion of the intervention.ConclusionsPFJ OA participants were adherent to the supervised sessions of the intervention. Improvement in symptoms, physical performance, and muscle torque were found after 6 weeks. Participant retention at 6 months was fair, and significant changes were no longer present. Our findings suggest that a hip strengthening and core stabilization program may be beneficial to improve symptoms, function, and physical performance in persons with PFJ OA. Future studies are needed, and additional measures should be taken to improve long-term adherence to exercise.Trial registrationClinicalTrials.gov NCT02825238. Registered 6 July 2016 (retrospectively registered).

Repeatability and discrimination validity of cartilage imaging biomarkers for experimental medicine studies of knee osteoarthritis

PURPOSE The utility of magnetic resonance imaging (MRI) quantitative imaging biomarkers (QIBs) of cartilage in experimental medicine studies of potential disease modifying osteoarthritis treatments (DMOATs) is uncertain due to the small sample sizes and short follow-up involved. To be relevant to such studies, candidate QIBs must demonstrate acceptable repeatability, discriminative ability and responsiveness. The purpose of this study was to evaluate test-retest repeatability and discriminative ability of 4 cartilage QIBs at the knee (thickness, T1rho, T2 and delayed gadolinium enhanced MRI of cartilage [dGEMRIC]) to assess their utility in experimental medicine studies. METHODS We imaged 9 participants with mild-moderate knee osteoarthritis (OA), characterised by radiographs with medial tibiofemoral predominant disease and Kellgren-Lawrence grades 2-3, and 4 healthy volunteers (HVs) matched for age, sex and body mass index. Participants were imaged at baseline and 1 month. MR studies were performed on a 3T system (MR 750, GE Healthcare) and were split into 2 sessions. The first MR session included a 3-dimensional spoiled gradient echo (3D SPGR) sequence and T1rho and T2 mapping sequences. At the end of this session, we administered an intravenous gadolinium based contrast agent (Dotarem, Guerbet LLC) at double dose (0.2 mmol/kg). Participants then performed 10 minutes of exercise on a stationary cycle to facilitate contrast penetration into the joint for dGEMRIC. The second MR session began 90 minutes following injection of contrast agent and consisted of T1 mapping using a variable flip angle technique. MR pulse sequence details are provided in table 1. We performed surface based analysis of cartilage parameters using Stradwin software (http://mi.eng.cam.ac.uk/~rwp/stradwin). In brief, this consists of semi-automated thickness measurement on 3D SPGR images, with generation of accurate inner and outer cartilage surfaces. Following rigid registration of the compositional (T1rho, T2, dGEMRIC) data to the 3D SPGR images, the same surfaces were used to sample the compositional data. This analysis pipeline allows each parameter to be measured at ~5,000 surface vertices per participant. We assessed overall (pooled OA and HV data) test-retest repeatability by calculating the root-mean-square coefficient of variation (RMS-CV) and the smallest detectable change (SDC) for each parameter. We assessed overall discriminative validity by estimating effect sizes for the difference in the mean value of each parameter in OA participants and HVs. We also mapped the test-retest errors and mean difference in each parameter between groups onto a representative surface for each cartilage region. RESULTS Participant characteristics are provided in table 2. RMS-CVs, SDCs and effect size estimates are provided in table 3. Overall test-retest RMS-CV values ranged from 2.5% (T1rho) to 10.3% (dGEMRIC). The largest overall effect size was demonstrated for dGEMRIC (-1.3, 90% confidence interval [CI] -2.3 to -0.2), followed by thickness (-0.67, 90% CI -1.5 to 0.3), T1rho and T2 (both 0.61, 90% CI -0.4 to 1.5). Mapping of test-retest errors and between-group differences to a representative surface revealed substantial spatial heterogeneity in these metrics for all parameters (figure 1). This suggests that surface based approaches may offer improved sensitivity over traditional region of interest based measurements. CONCLUSION This study demonstrates that cartilage QIBs may be useful in experimental medicine studies of knee osteoarthritis. Statistical approaches reflecting the spatial heterogeneity of changes in cartilage should be used to provide an indication of where significant results are located, not just whether an average value is significantly different. Future work will evaluate responsiveness of these cartilage QIBs.

Osteoarthritis-related walking disability and cardiovascular disease risk

Purpose: While osteoarthritis (OA)-related morbidity is well known, the association between OA and increased cardiovascular disease (CVD) risk is not fully elucidated. Arterial stiffness is a validated marker of cardiovascular risk and a predictor of mortality. However, evidence suggests physical exercise reduces arterial stiffness, indicating that arterial stiffness can be modified. Moreover, it seems clear that OA disability increases the risk of CVD beyond what can be explained by common risk factors like ageing and obesity. Hence, the objectives in this study were to compare walking ability in a population-based OA cohort with age- and gender-matched peers from the general population, and to explore the associations between walking ability and CVD risk measured as arterial stiffness in the OA cohort. Methods: This cross-sectional study included participants (40-80 years) who self-reported OA (n = 500) in a population-based study and matched peers from the general population (n = 370). Both groups performed the 6 min walk distance-test (6 MWD) according to the American Thoracic Society statement guidelines. Further, participants who self-reported OA completed comprehensive clinical examinations and were classified according to the American College of Rheumatology criteria by a medical doctor. In addition, data on demographic (age, gender, body mass index, smoking habits, education level) and clinical characteristics (non-steroidal anti-inflammatory drugs, Numeric Rating Scale of Joint pain) were collected. Arterial stiffness determined by carotid-femoral Pulse Wave Velocity was measured using a non-invasive gold standard method. Pulse Wave Velocity and resting heart rate were assessed using the Sphygomocor apparatus (Atcor, Australia). Brachial blood pressure was measured after 5 min rest, using the OMRON M7 (Kyoto, Japan). Group difference in 6 MWD was calculated with t-test, and the association between 6 MWD and CVD risk (arterial stiffness) in the OA cohort was explored in multivariate regression models. Results: The mean (SD) age of the OA-participants was 63.2 (8.8) years, 28% were men. More than 2/3 (68.4%) were classified with overweight or obesity, and one in four of the participants reported using non-steroidal anti-inflammatory drugs on a daily basis. Most participants (78%) described joint pain of five or lower on the Numeric Rating Scale. In total, 347 participants (69.4%) were classified with OA in one or more joint(s) according to the American College of Rheumatology criteria. Mean (SD) arterial stiffness (Pulse Wave Velocity) in the OA- group was 8.82 (2.06) m/s, ranging from 4.65 to 18.30 m/s. Compared to the general population, OA participants achieved a significantly shorter 6 MWD (551.4 m vs. 615.3 m, P < 0.001). In age stratified analyses, the largest mean difference in 6 MWD was observed in the youngest age group (40–49 years) (594.9 m vs. 685.3 m, P < 0.001) (Figure 1). These differences attenuated gradually with increasing age. In the OA group, the 6 MWD was significantly associated to arterial stiffness (Pulse Wave Velocity) in adjusted analysis (P = 0.001); 100 m longer walking distance corresponded to 0.3 m/s reduction in arterial stiffness. Conclusions: Already from the age of forty, people with OA have significantly shorter walking distance compared to age matched peers, underlining the importance of early clinical approach to OA. Further, in the OA-group, the 6 MWD was significantly associated with arterial stiffness, suggesting that walking disability is important for the CVD risk profile in OA.

Long-term effects of vitamin d supplementation and maintaining vitamin d sufficiency on knee osteoarthritis over 5 years

Purpose: Epidemiological studies suggest that vitamin D deficiency is associated with knee symptom and structural progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) failed to demonstrate a significant effect of vitamin D supplementation on OA, probably due to selecting OA participants with and without vitamin D deficiency, short duration of the studies and a large proportion of participants in the placebo group reaching vitamin D sufficiency (61.3% of patients in the placebo group achieved a serum 25-hydroxyvitamin D [25(OH)D] level of > 60 nmol/l at 3 months of a clinical trial). We conducted the Vitamin D Effect on Osteoarthritis (VIDEO) clinical trial by selecting knee OA participants with vitamin D insufficiency and reported that there was no significant effect of vitamin D supplementation over 2 years on cartilage volume loss and knee pain assessed using the WOMAC scale. However, there was a significant reduction in knee pain evaluated by VAS knee pain scale, an improvement in physical function and a decrease in joint effusion-synovitis volume and bone marrow oedema compared to the placebo group. We aimed to describe the effect of vitamin D supplementation for 2 years on knee symptoms compared to placebo after 3 years of cessation of treatment, and to examine whether those maintaining sufficient serum vitamin D levels over 5 years had reduced knee symptoms compared with those who did not maintain adequate vitamin D levels over 5 years in patients with knee OA. Methods: Participants with symptomatic knee OA and low 25(OH)D (12.5-60 nmol/l) were enrolled in the VIDEO clinical trial. Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years. 172 participants who enrolled in the study from Hobart were followed up after 3 years (5 years from baseline) of the cessation of the treatment to assess knee symptoms and vitamin D levels. Participants with serum 25(OH)D measurements at month 0, 3, 24 and 60 and were included in the post-hoc analyses. The incidence of total knee replacement was recorded and they were excluded from the symptom analyses. Participants were classified as maintaining sufficient vitamin D group if they maintained serum 25(OH)D >50 nmol/l at month 3, 24 and 60 (n = 79), and not maintaining sufficient vitamin D group (25[OH]D ≤50 nmol/l at month 3, 24 and 60, n = 62). Knee symptoms were assessed at baseline, 3, 6, 12, 24 and 60 months using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results: The level of 25(OH)D dropped in the vitamin D group (from 87.0 nmol/l to 53.3 nmol/l) over 3 years after the cessation of the treatment. Placebo group slightly increased the vitamin D level (53.3 nmol/l to 61.7 nmol/l) over 3 years. Knee pain increased from the end of the study (2nd year) to 5 years of follow-up in the treatment (81.8 to 91.7) and placebo (75.8 to 101.1) groups. 16.7% of the participants in vitamin D and 18.5% of the participants in placebo group underwent total knee replacement surgery. There were no significant differences in WOMAC pain, stiffness or dysfunction scores and total knee replacement surgery rates or change in symptom between Vitamin D and placebo groups after 3 years of cessation of the supplementation. However, participants who maintained adequate vitamin D levels over 5 years had significantly less WOMAC knee pain (β: −38.4, 95% CI: −69.2, −7.7) and physical dysfunction (β: −98.5, 95% CI: −193.8, −3.1) than participants with vitamin D deficiency over 5 years in multivariable analyses after adjusting for age, sex and BMI.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusions: Vitamin D supplementation over 2 years did not result in significant differences in change in knee symptom score over 5 years compared to placebo. However, knee OA patients maintaining sufficient serum vitamin D levels over long-term had more improvement in knee pain and physical function than those who did not maintain adequate vitamin D levels, suggesting a beneficial effect of maintaining sufficient serum vitamin D for knee OA.

Monocyte activation is elevated in women with knee-osteoarthritis and associated with inflammation, BMI and pain.

Monocytes contribute to synovitis and disease pathogenesis in osteoarthritis (OA). Low-grade inflammation occurs in OA and correlates with disease severity and progression. Since monocyte development and function is altered by systemic inflammation, we analyzed monocyte numbers and function between individuals with knee OA and healthy age- and sex-matched controls. We analyzed markers of soluble and cellular inflammation in peripheral blood of women with knee OA and compared them to healthy age- and sex-matched controls. Soluble inflammatory mediators (TNF, IL-6, IL-10 and CRP) in the serum were measured by high-sensitivity ELISA. Leukocyte numbers, surface expression of monocyte activation markers, and monocyte production of pro-inflammatory mediators (TNF and IL-1β) following stimulation were measured by flow cytometry. Women with knee OA (n=15) had elevated levels of serum c-reactive protein (CRP) and a lower proportion of circulating monocytes. Monocytes from OA participants had elevated expression of the activation markers CD16, CCR2, and HLA-DR and induced greater production of tumor necrosis factor (TNF) and IL-1β compared to healthy controls. Higher serum TNF and BMI were correlated with increased monocyte expression of CCR2. Additionally monocyte CCR2 expression and serum TNF were correlated with worse pain on a validated questionnaire. Our findings suggest monocytes are activated prior to their entry into the synovium. Modulating systemic inflammation and monocyte recruitment to the synovium could be of therapeutic benefit.

The AUSCAN and PRWHE Demonstrate Comparable Internal Consistency and Validity in Patients With Early Thumb Carpometacarpal Osteoarthritis

The Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Patient-Rated Wrist-Hand Evaluation (PRWHE) are 2 patient-related outcome measures to assess pain and disability in patients with osteoarthritis (OA). The purpose of this study was to evaluate the AUSCAN and PRWHE in a large-scale, longitudinal cohort of patients with early thumb carpometacarpal (CMC) OA. We obtained baseline data on 135 individuals (92 with early CMC OA participants and 43 asymptomatic controls) and at follow-up (year 1.5) on 83 individuals. We assessed the internal consistency using Cronbach alpha, and construct and criterion validity using other pain scales and objective measures of strength, respectively. We also examined the correlation between the AUSCAN and PRWHE and correlation coefficients at baseline and follow-up, as well as the correlation between changes in these instruments over the follow-up period. Internal consistency was high for both AUSCAN and PRWHE totals and subscales (Cronbach α > 0.70). Both instruments demonstrated construct validity compared with the Verbal Rating Scale ( r = 0.52-0.60, P < .01), an assessment of pain, and moderate criterion validity compared with key pinch and grip strength ( r = -.24 to -.33, P < .05). These instruments were highly correlated with each other at baseline and follow-up time points ( r = 0.76-.94, P < .01), and changes in a patient's total scores over time were also correlated ( r = 0.83, P < .01). The AUSCAN and PRWHE are both valid assessments for pain and/or disability in patients with early thumb CMC OA.

Cold Pain Threshold Identifies a Subgroup of Individuals With Knee Osteoarthritis That Present With Multimodality Hyperalgesia and Elevated Pain Levels.

Objectives:Cold hyperalgesia has been established as an important marker of pain severity in a number of conditions. This study aimed to establish the extent to which patients with knee osteoarthritis (OA) demonstrate widespread cold, heat, and pressure hyperalgesia. OA participants with widespread cold hyperalgesia were compared with the remaining OA cohort to determine whether they could be distinguished in terms of hyperalgesia, pain report, pain quality, and physical function.Methods:A total of 80 participants with knee OA and 40 matched healthy, pain-free controls participated. OA participants completed a washout of their usual medication. Quantitative sensory testing was completed at 3 sites using standard methods. Cold pain threshold (CPT) and heat pain thresholds (HPT) were tested using a Peltier thermode and pressure pain thresholds (PPT) using a digital algometer. All participants completed the short-form health survey questionnaire and OA participants completed the PainDETECT, Western Ontario and McMaster Universities Osteoarthritis Index of the Knee (WOMAC), and pain quality assessment scale questionnaires.Results:OA participants demonstrated widespread cold hyperalgesia (P<0.0001), had lower PPT at the index knee (P<0.0001) compared with controls and reported decreased physical health on the SF-36 (P=0.01). The OA subcohort with high global CPT (≥12.25°C) exhibited multimodality sensitization compared with the remaining OA cohort (PPT P<0.0001; CPT P<0.0001; HPT P=0.021 index knee). This group also reported increased pain, decreased function, and more features of neuropathic pain.Discussion:This study identified a specific subgroup of patients with knee OA who exhibited widespread, multimodality hyperalgesia, more pain, more features of neuropathic pain, and greater functional impairment. Identification of patients with this pain phenotype may permit more targeted and effective pain management.

Variable compensation during the sit-to-stand task among individuals with severe knee osteoarthritis

BackgroundIndividuals with knee osteoarthritis (OA) show variability during the sit-to-stand (STS) task, so they may not perform the STS in the same way. This study aimed to determine whether individuals with knee OA have different strategies in performing the STS. MethodsParticipants with knee OA and able-bodied individuals underwent STS evaluation at a self-selected pace with use of a motion measurement system consisting of 12 cameras and 2 force plates. ResultsIn total, 101 participants (57 women) with knee OA showed 3 main STS strategies. As compared with the 27 controls (14 women), 24 OA participants, compensated STS, showed greater trunk flexion (47.1° vs. 38.3°; P<0.01) and trunk obliquity (4.6° vs. –0.8°; P<0.001) when completing the STS task in the same amount of time as controls (2.4 vs. 2.7s; P=0.999). The second group (n=59), inadequately compensated STS, also compensated with trunk flexion (47.7° vs. 38.3°; P<0.01) and trunk obliquity (1.6° vs. –0.8°; P<0.001) but took longer than controls (3.4 vs. 2.7s; P=0.001). The third group (n=18), severe impaired STS, took an extended amount of time to execute the STS (6s), with marked trunk flexion (59.2°) and obliquity (4.1°), so participants in this group were perhaps severely impaired in completing the STS. ConclusionThis study identified 3 groups STS trunk strategies among participants with STS. Moreover, the data reveal a concise representation of the relations among strategy variables. The findings could be used to simplify the characterization of the STS among patients with knee OA and aid with follow-up.

Hip biomechanics during stair ascent and descent in people with and without hip osteoarthritis.

Hip osteoarthritis (OA) is often associated with pain and impaired function. Understanding biomechanical alterations in patients with hip OA during challenging activities such as stair use is important to inform treatments. The aim of this study was to determine whether kinematics and kinetics during stair ambulation differed between people with hip OA and healthy controls. Fifteen participants with symptomatic and radiographic hip OA and 15 asymptomatic healthy controls underwent 3-D motion analysis during stair ascent and descent. Trunk, pelvis, and hip kinematics as well as hip kinetics were evaluated. Analyses were performed unadjusted and adjusted for speed and leg length. In both the unadjusted and adjusted analyses, participants with hip OA ascended stairs with less hip range of motion in all three planes and a lower peak external rotation moment compared to controls. In the unadjusted analysis, hip OA participants descended stairs with greater ipsilateral trunk lean, less sagittal plane range of motion, lower peak extension moment, lower peak external rotation moment, and greater hip adduction moment impulse compared to controls. In the adjusted results, peak internal rotation moment and hip adduction moment impulse were greater in hip OA participants compared to controls. Findings show that individuals with hip OA display limited range of hip joint movement, particularly during stair ascent, and overall indicate the use of strategies (e.g., trunk lean; lower peak external rotation moment; higher adduction moment impulse) that implicate altered hip abductor function. Future research is required to further understand the implications of these findings on hip OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1505-1514, 2017.

To assess differential features of marrow adiposity between postmenopausal women with osteoarthritis and osteoporosis using water/fat MRI.

To assess the differential features of marrow adiposity between osteoarthritis (OA) and osteoporosis (OP) in postmenopausal women using water/fat MRI. This cross-sectional study included 97 postmenopausal women (OA [n = 25], OA + osteopenia [n = 27], OA + OP [n = 23], and OP groups [n = 22]). Water/fat MRI, dual-energy x-ray absorptiometry and biochemical analysis were performed to assess vertebral marrow fat fraction, bone mineral density, and bone biomarkers, respectively. Harris Hip Score was recorded to evaluate hip function. There were significant differences in marrow fat content among the OA, OA + osteopenia, and OA + OP groups, between OP and OA participants with normal bone mass or osteopenia (all P < 0.05); no significant difference was observed between OA + OP and OP groups. Serum levels of leptin and β-Crosslaps in OA with normal bone mass and osteopenic OA groups were higher than in OP group. Marrow fat fraction was inversely correlated with Harris Hip Score (r = -0.371, P = 0.013), bone mineral density (r = -0.554, P = 0.009) and leptin levels (r = -0.610, P < 0.001). In multivariate regression analysis, marrow fat fraction was found to have a consistent and unchanged inverse association with leptin levels (Sβ = -0.311, P = 0.002) and bone mineral density (Sβ = -0.265, P = 0.006) after adjusting for age, years since menopause, and body mass index. Postmenopausal OA with OP have a phenotype with higher marrow adiposity. OA and OP could coexist, for the presence of a specific subgroup of OA with increased marrow fat accumulation and high risk of developing OP.

Hip abductor muscle volume in hip osteoarthritis and matched controls

Hip abductor muscle strength and function is negatively impacted by the presence of hip osteoarthritis (OA). This study aimed to quantify differences in hip abductor muscle volume, fatty infiltration and strength in a unilateral hip OA population when compared to a control group. Impact of radiographic severity of OA on these variables was also examined. Volumes of gluteus maximus (GMax), medius (GMed) minimus (GMin) and tensor fascia lata (TFL) was measured using MRI and muscle volume asymmetry between limbs was calculated. Fatty infiltrate within muscles was graded using the Goutallier classification system. Hip abduction and rotation strength was tested using a dynamometer. Differences between groups or limbs were analysed using t-tests and differences in fatty infiltration using non-parametric tests. A statistically significant decrease in muscle volume was identified in GMax (P<0.01), GMed (P<0.02) and GMin (P<0.01) on the affected side in the OA group compared to both the contralateral side and the control group and differences were related to severity of OA. Hip abduction and internal rotation strength was reduced in the OA group. Increased levels of fatty infiltration were identified in the affected limbs of the OA group for GMax (P=0.01) and GMin (P=0.04). Gluteal muscle atrophy, increased gluteal fatty infiltration and hip strength deficits were evident in the affected hips of OA participants. Since severity of OA was related to the extent of atrophy and fatty deposits, rehabilitation programs targeting these muscles could reverse or halt the progression of these structural and functional deficits.

Polymorphisms in ADAMTS4 and ADAMTS5 are not linked to susceptibility to knee osteoarthritis in the Turkish population.

Considering the functions of aggrecanase-1 (ADAMTS4) and -2 (ADAMTS5), which are thought to be the two major enzymes responsible for the destruction of aggrecans in arthritic diseases, we investigated whether important polymorphisms in the ADAMTS4 and ADAMTS5 genes affect osteoarthritis (OA) susceptibility. Our study took place in Mugla, Turkey. Ninety-five cases were recruited following OA diagnosis (72 women and 23 men), and 80 individuals without any symptoms or radiographic signs of OA (56 women and 24 men) were chosen as healthy controls. After obtaining DNA from patients and control subjects, ADAMTS4 and ADAMTS5 genotypes were determined using the ABI Prism StepOnePlus Real-Time system. In addition, we categorized patients based on OA grade. There were no significant differences in the genotype distributions of the four polymorphisms between the groups (P > 0.05). Moreover, ADAMTS4 and ADAMTS5 allele frequencies did not differ between OA and control participants (P > 0.05). These findings suggest that the ADAMTS4 (rs4233367 and rs11807350) and ADAMTS5 (rs226794 and rs2830585) variants examined may not contribute to susceptibility to knee OA in the Turkish population. Other gene polymorphisms should be assessed in order to explain variations in OA susceptibility.