Digital self-management, analgesic use and patient-reported outcomes in knee or hip osteoarthritis.

OBJECTIVE: To investigate changes in analgesic use before and after participation in a digital first-line treatment program (exercise and patient education) in persons with knee or hip OA and to explore associations between these changes in medication use and participant-reported pain and function. DESIGN: Retrospective cohort study with pre-post measures. SETTING: Community setting, Sweden. PARTICIPANTS: Individuals (n=4100, mean [SD] age 64.5 [9.3], 73.3% females) participating in the digital program. INTERVENTIONS: A digital supervised education and exercise therapy. MAIN OUTCOME MEASURES: Self-reported analgesic use for knee/hip pain during the past month at baseline and 12-week follow-up, knee/hip NRS pain (0-10, a higher value indicating more pain), and KOOS-12 or HOOS-12 Function subscale (0-100, higher values indicating better function). McNemar test, multivariable logistic regression and linear random intercept model were used for statistical analyses. RESULTS: Among participants, 61.4% and 49.4% were analgesic users at baseline and 12-week follow up, respectively, (absolute reduction 12.0%, 95%CI 10.5, 13.5). Being female, having hip OA, lower education, higher body mass index, living outside large metropolitan cities, co-existing rheumatoid arthritis, and walking difficulties were associated with higher odds of analgesic use at baseline. At both time points, persons not using analgesics at the time reported better outcomes. All groups but "new users" experienced improvements in their pain and function following participation in digital program with the greatest improvements observed among "quitters". CONCLUSION: Engaging in a digital exercise and patient education program as a primary treatment for knee or hip osteoarthritis was associated with a reduction in the use of analgesics. The greatest improvements were seen for those who stopped analgesic use. These results highlight the importance of providing effective first-line treatment to people with knee or hip OA.

A scoping review of how early-stage knee osteoarthritis has been defined.

BACKGROUND: Early-stage knee osteoarthritis (KOA) classification criteria will enable consistent identification and trial recruitment of individuals with knee osteoarthritis (OA) at an earlier stage of the disease when interventions may be more effective. Toward this goal, we identified how early-stage KOA has been defined in the literature. METHODS: We performed a scoping literature review in PubMed, EMBASE, Cochrane, and Web of Science, including human studies where early-stage KOA was included as a study population or outcome. Extracted data included demographics, symptoms/history, examination, laboratory, imaging, performance-based measures, gross inspection/histopathologic domains, and the components of composite early-stage KOA definitions. RESULTS: Of 6142 articles identified, 211 were included in data synthesis. An early-stage KOA definition was used for study inclusion in 194 studies, to define study outcomes in 11 studies, and in the context of new criteria development or validation in six studies. The element most often used to define early-stage KOA was Kellgren-Lawrence (KL) grade (151 studies, 72%), followed by symptoms (118 studies, 56%), and demographic characteristics (73 studies, 35%); 14 studies (6%) used previously developed early-stage KOA composite criteria. Among studies defining early-stage KOA radiographically, 52 studies defined early-stage KOA by KL grade alone; of these 52, 44 (85%) studies included individuals with KL grade 2 or higher in their definitions. CONCLUSION: Early-stage KOA is variably defined in the published literature. Most studies included KL grades of 2 or higher within their definitions, which reflects established or later-stage OA. These findings underscore the need to develop and validate classification criteria for early-stage KOA.

A White Paper on Collagen Hydrolyzates and Ultrahydrolyzates: Potential Supplements to Support Joint Health in Osteoarthritis?

PURPOSE OF REVIEW: Osteoarthritis (OA) is the most common forms of arthritis in the general population, accounting for more pain and functional disability than any other musculoskeletal disease. There are currently no approved disease modifying drugs for OA. In the absence of effective pharmacotherapy, many patients with OA turn to nutritional supplements and nutraceuticals, including collagen derivatives. Collagen hydrolyzates and ultrahydrolyzates are terms used to describe collagens that have been broken down into small peptides and amino acids in the presence of collagenases and high pressure. RECENT FINDINGS: This article reviews the relevant literature and serves as a White Paper on collagen hydrolyzates and ultrahydrolyzates as emerging supplements often advertised to support joint health in OA. Collagen hydrolyzates have demonstrated some evidence of efficacy in a handful of small scale clinical trials, but their ability to treat and reverse advanced joint disease remains highly speculative, as is the case for other nutritional supplements. The aim of this White Paper is to stimulate research and development of collagen-based supplements for patients with OA and other musculoskeletal diseases at academic and industrial levels. This White Paper does not make any treatment recommendations for OA patients in the clinical context, but simply aims to highlight opportunities for scientific innovation and interdisciplinary collaboration, which are crucial for the development of novel products and nutritional interventions based on the best available and published evidence.

Early-stage symptomatic osteoarthritis of the knee - time for action.

Osteoarthritis (OA) remains the most challenging arthritic disorder, with a high burden of disease and no available disease-modifying treatments. Symptomatic early-stage OA of the knee (the focus of this Review) urgently needs to be identified and defined, as efficient early-stage case finding and diagnosis in primary care would enable health-care providers to proactively and substantially reduce the burden of disease through proper management including structured education, exercise and weight management (when needed) and addressing lifestyle-related risk factors for disease progression. Efforts to define patient populations with symptomatic early-stage knee OA on the basis of validated classification criteria are ongoing. Such criteria, as well as the identification of molecular and imaging biomarkers of disease risk and/or progression, would enable well-designed clinical studies, facilitate interventional trials, and aid the discovery and validation of cellular and molecular targets for novel therapies. Treatment strategies, relevant outcomes and ethical issues also need to be considered in the context of the cost-effective management of symptomatic early-stage knee OA. To move forwards, a multidisciplinary and sustained international effort involving all major stakeholders is required.

Towards classification criteria for early-stage knee osteoarthritis: A population-based study to enrich for progressors.

OBJECTIVE: To facilitate a greater likelihood of favorable response to new disease-modifying therapies, recruitment of patients at an earlier stage of their disease into clinical trials may be an attractive strategy. Hence, there is a need to develop widely accepted classification criteria for early-stage knee osteoarthritis (OA). We have proposed a set of classification criteria for early-stage knee OA (2018 classification criteria) now being further refined. Here, we test the draft criteria for enrichment for clinical and structural progression. DESIGN: Performance of the 2018 classification criteria for early stage knee OA was tested using data from the Osteoarthritis Initiative (OAI). The OAI comprises data of 4796 men and women aged 45-79 years with or at risk for knee OA at baseline. Based on the 2018 classification criteria, a knee with Kellgren & Lawrence (K&L) grade of 0-I, two out of four Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales equal or less than 85, and presence of at least one of joint line tenderness or crepitus, was considered as early-stage knee OA. Knees with K&L grade 0-I that did not fulfill the 2018 criteria, were considered as controls. Logistic regression analysis was used to evaluate the predictive performance of the criteria set for structural as well as clinical progression. We further explored the discriminatory capability of criteria by including the average KOOS4 score, and relevant clinical examination findings such as the presence of effusion and/or Heberden's nodes. RESULTS: We identified 1315 (27%) knees from OAI fulfilling the 2018 early-stage knee OA classification criteria. The female to male ratio was higher in the early knee OA group compared to controls. The early-stage knee OA group were on average slightly younger and had higher body mass index vs controls (mean [SD] age: 59.2 [8.9] years vs. 60.2 [9.1] and mean [SD] BMI 28.3 [7.0] vs. 26.8 [6.0]). By applying the 2018 criteria, there was a substantial enrichment compared to controls at 48 and 96 months for both structural (OR=1.1-1.4, and AUC=0.72-0.74) and clinical progressors (OR=2.1-2.5, 95% and AUC=0.66). Expanding the clinical examination findings by including joint effusion and/or Heberden's nodes improved the enrichment for both structural and clinical progressors (OR=4.2, 95% confidence interval=3.2-5.5 and OR=3.3, 95% confidence interval=2.8-3.5, respectively). Replacing scoring of the 4 separate KOOS domains by a KOOS4 score performed comparably. CONCLUSIONS: The proposed 2018 early-stage knee OA classification criteria showed encouraging performance characteristics with regard to an enrichment for structural and clinical progression using longitudinal OAI data. Our results indicate that the addition of clinical findings improves the performance of previous criteria to define early-stage disease and risk for progression.

Establishing outcome measures in early knee osteoarthritis.

The classification and monitoring of individuals with early knee osteoarthritis (OA) are important considerations for the design and evaluation of therapeutic interventions and require the identification of appropriate outcome measures. Potential outcome domains to assess for early OA include patient-reported outcomes (such as pain, function and quality of life), features of clinical examination (such as joint line tenderness and crepitus), objective measures of physical function, levels of physical activity, features of imaging modalities (such as of magnetic resonance imaging) and biochemical markers in body fluid. Patient characteristics such as adiposity and biomechanics of the knee could also have relevance to the assessment of early OA. Importantly, research is needed to enable the selection of outcome measures that are feasible, reliable and validated in individuals at risk of knee OA or with early knee OA. In this Perspectives article, potential outcome measures for early symptomatic knee OA are discussed, including those measures that could be of use in clinical practice and/or the research setting.

Towards secondary prevention of early knee osteoarthritis.

Osteoarthritis (OA) of the knee is the most common arthritic disease, yet a convincing drug treatment is not available. The current narrative review focuses on integration of scientific evidence and professional experience to illustrate which management approaches can be taken for prototypical individual patient profiles with early knee OA. Animal models suggest that: (1) OA can progress even in the presence of fully recovered movement kinetics, kinematics and muscle activation patterns; (2) muscle weakness is an independent risk factor for the onset and possibly the rate of progression of knee OA; (3) onset and progression of OA are not related to body weight but appear to depend on the percentage of body fat. From studies in the human model, one could postulate that risk factors associated with progression of knee OA include genetic traits, preceding traumatic events, obesity, intensity of pain at baseline, static and dynamic joint malalignment and reduced muscle strength. Taken this into account, an individual can be identified as early knee OA at high risk for disease progression. A holistic patient-tailored management including education, supportive medication, weight loss, exercise therapy (aerobic, strengthening and neuromuscular) and behavioural approaches to improve self-management of early knee OA is discussed in individual prototypic patients. Secondary prevention of early knee OA provides a window of opportunity to slow down or even reverse the disease process. Yet, as the sheer number of patients early in the OA disease process is probably large, a more structured approach is needed to provide appropriate care depending on the patient's individual risk profile.

Changes in gait characteristics of women with early and established medial knee osteoarthritis: Results from a 2-years longitudinal study.

BACKGROUND: Despite the large number of cross-sectional studies on gait in subjects with knee osteoarthritis, there are scarcely any longitudinal studies on gait changes in knee osteoarthritis. METHODS: Gait analysis was performed on 25 women with early and 18 with established medial knee osteoarthritis, as well as a group of 23 healthy controls. Subjects were asked to walk at their comfortable speed. Kinematic and kinetic data were measured at baseline and after 2years follow-up. FINDINGS: Results indicated that the early osteoarthritis group, similar to established osteoarthritis group, showed significantly higher maximum knee adduction angles compared to the controls during the early stance phase of gait. None of the kinematic or kinetic measures, changed over two years in the early osteoarthritis group. In the established osteoarthritis group, at the time of entry, an increased first and second peak knee adduction moment, as well as higher mid-stance knee adduction moment and knee adduction moment impulse, were present compared to the control and the early osteoarthritis groups. Mid-stance knee adduction moment and knee adduction moment impulse, further increased over two years only in the established osteoarthritis group. For all three groups, the peak knee flexion angle during the stance phase decreased significantly over time. INTERPRETATION: Increased maximum knee adduction angle during stance phase was the only alteration in the gait pattern of subjects with early knee osteoarthritis compared to the controls. This suggests that, unlike in the later stages of the disease, gait is rather stable over two years in early osteoarthritis.

Do Psychosocial Factors Predict Muscle Strength, Pain, or Physical Performance in Patients With Knee Osteoarthritis?

OBJECTIVE: The aim of this study was to examine the relationship of psychosocial factors, namely, pain catastrophizing, kinesiophobia, and maladaptive coping strategies, with muscle strength, pain, and physical performance in patients with knee osteoarthritis (OA)-related symptoms. METHODS: A total of 109 women (64 with knee OA-related symptoms) with a mean age of 65.4 years (49-81 years) were recruited for this study. Psychosocial factors were quantified by the Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, and Pain Coping Inventory. Clinical features were assessed using isometric and isokinetic knee muscle strength measurements, visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index, and functional tests. Associations were examined using correlation and regression analysis. RESULTS: In knee OA patients, pain catastrophizing, kinesiophobia, and coping strategy explained a significant proportion of the variability in isometric knee extension and flexion strength (6.3%-9.2%), accounting for more overall variability than some demographic and medical status variables combined. Psychosocial factors were not significant independent predictors of isokinetic strength, knee pain, or physical performance. CONCLUSIONS: In understanding clinical features related to knee OA, such as muscle weakness, pain catastrophizing, kinesiophobia, and coping strategy might offer something additional beyond what might be explained by traditional factors, underscoring the importance of a biopsychosocial approach in knee OA management. Further research on individual patient characteristics that mediate the effects of psychosocial factors is, however, required in order to create opportunities for more targeted, personalized treatment for knee OA.

Dynamic and static knee alignment at baseline predict structural abnormalities on MRI associated with medial compartment knee osteoarthritis after 2 years.

BACKGROUND: Dynamic and static varus alignment, both, have been reported as risk factors associated with structural progression of knee osteoarthritis. However the association of none of the static and dynamic alignment with structural, clinical, and functional progression associated with knee osteoarthritis has not been assessed yet in a longitudinal study. METHODS: Forty-seven women with early and established medial knee osteoarthritis were evaluated. Static and dynamic alignment as well as MRI detected structural features, clinical, and functional characteristics of patients were assessed at baseline and at 2 years follow-up. Associations between baseline static and dynamic alignment with structural, functional, and clinical characteristics at the time of entry, as well as the changes over 2 years were evaluated. FINDINGS: Both static and dynamic varus alignment at baseline were significantly associated with osteoarthritis related tibio-femoral joint structural abnormalities detected on MRI, at the time of entry. Only the magnitude of varus thrust at baseline was predictive of the changes in the presence of meniscal maceration over two years. None of the static or dynamic measures of knee joint alignment were associated with clinical characteristics associated with medial knee osteoarthritis. INTERPRETATION: The key finding of this study is that both frontal plane dynamic and static alignment, are associated with structural abnormalities in patients with medial knee osteoarthritis.

Varus thrust in women with early medial knee osteoarthritis and its relation with the external knee adduction moment.

BACKGROUND: Varus thrust, defined as an abrupt increase of the knee varus angle during weight-bearing in gait, has been shown to be present in patients with moderate to severe knee osteoarthritis and is considered to be one of the risk factors for progression of symptomatic medial knee osteoarthritis. We evaluated the presence and magnitude of varus thrust and its relation with the Knee Adduction Moment in women with early medial knee osteoarthritis, and compared it to that in a group of controls and in a group of subjects with established medial knee osteoarthritis. METHODS: Twenty-seven women with early medial knee osteoarthritis, 20 women with established medial knee osteoarthritis and 24 asymptomatic controls were evaluated. Varus thrust was estimated as an increase of the knee varus angle during the weight-bearing phase of gait at self-selected speed, assessed by 3D motion analysis. FINDINGS: Varus thrust was significantly higher in both early and established osteoarthritis groups compared to the control group (P<0.001), but not different between osteoarthritis groups. While the knee adduction moments were higher than controls only in the established osteoarthritis group, the magnitude of varus thrust was significantly correlated with the second peak knee adduction moment. INTERPRETATION: Higher varus thrust was found both in early and established stages of knee osteoarthritis, suggesting that problems with dynamic stabilization of the knee are present early in the development of knee osteoarthritis. This highlights the necessity of considering dynamic alignment in rehabilitation already in the early stages of the disease.

Changes in proprioceptive weighting during quiet standing in women with early and established knee osteoarthritis compared to healthy controls.

OBJECTIVES: Knee osteoarthritis (OA) is highly prevalent in people above the age of 60, and is typically associated with pain, stiffness, muscle weakness and proprioceptive deficits. Muscle-tendon vibration has been used to assess the spatial reweighting of proprioceptive input during standing. The current study aimed to investigate whether weighting of proprioceptive input is altered in patients with early and established knee OA compared to asymptomatic controls. METHODS: The upright posture of 27 participants with early OA, 26 with established OA, and 27 asymptomatic controls was perturbed by vibrating (frequency: 70Hz and amplitude: approximately 0.5mm) ankle muscles (i.e. tibialis anterior and triceps surae) and knee muscles (vastus medialis). Center of pressure displacements of the participants were recorded using a force plate. RESULTS: Both patients with early and established OA were more sensitive to triceps surae vibration compared to their healthy peers (P<0.01 for both). No such difference was found for the vibration of tibialis anterior or vastus medialis muscles between patients with knee OA and healthy controls. CONCLUSIONS: These results suggest that the early stages of knee OA may already lead to reweighting of proprioceptive information, suggesting more reliance on ankle proprioceptive input for postural control.

Phase-dependent changes in local dynamic stability during walking in elderly with and without knee osteoarthritis.

Previously, we reported reduced time-averaged knee local stability, in the unaffected, but not the affected leg of elderly with knee osteoarthritis OA compared to controls. Since stability may show phase-related changes, we reanalyzed the dataset reported previously using time-dependent local stability, λ(t), and also calculated time-averaged local stability, λs, for comparison. We studied treadmill walking at increasing speeds, focusing on sagittal plane knee movements. 16 patients, 12 healthy peers and 15 young subjects were measured. We found a clear maximum in λ(t) (i.e. minimum in stability) at around 60% of the stride cycle (StanceMax λ(t)), a second clear maximum (SwingMax λ(t)) at around 95% followed by a minimum between 70% and 100% (SwingMin λ(t)). StanceMax λ(t) of both legs was significantly higher in the OA than the young control group. Values for healthy elderly fell between those of the other groups, were significantly higher than in young adults, but there was only a trend towards a significant difference with the StanceMax λ(t) of the OA group׳s affected side. Time-averaged and time-dependent stability measures within one leg were uncorrelated, while time-dependent stability measures at the affected side were inversely correlated with λs at the unaffected side. The results indicate that time-dependent local dynamic stability might provide a more detailed insight into the problems of gait stability in OA than conventional averaged local dynamic stability measures and support the notion that the paradoxical decline in unaffected side time-averaged local stability may be caused by a trade-off between affected and unaffected side stability.

Weak associations between structural changes on MRI and symptoms, function and muscle strength in relation to knee osteoarthritis.

PURPOSE: To explore associations between MRI-defined structural abnormalities and clinical features related to knee osteoarthritis (OA). METHODS: Structural and clinical knee OA features were assessed in 87 women (45 with knee OA symptoms). Structural features were quantified by the Kellgren and Lawrence grade on radiography and by the Boston-Leeds Osteoarthritis Knee Score on MRI. Clinical features were assessed using the Knee Injury and Osteoarthritis Outcome Score, functional tests and muscle strength measurements. Associations were examined using regression analyses. RESULTS: Limited significant associations between structural and clinical features were found. An increased meniscal signal was associated with more pain/symptoms (P < 0.027). An anterior cruciate ligament tear was associated with poorer stair climbing test performance (P = 0.045). In a stepwise linear regression model, patellofemoral cartilage integrity and pain explained 28 % of the isometric quadriceps strength variability. The amount of cartilage lesions, loose bodies and pain explained 38 % of the isokinetic quadriceps strength variability. Synovitis/effusion and patellofemoral cartilage integrity combined with pain explained 34 % of the isometric hamstring strength variability. CONCLUSION: Although MRI-detected cartilage lesions, synovitis/effusion and loose bodies did explain part of the muscle strength variability, results suggest that MRI does not improve the link between joint degeneration and the clinical expression of knee OA. MRI contributes less than expected to the understanding of pain and function in knee OA and possibly offers little opportunity to develop structure-modifying treatments in knee OA that could influence the patient's pain and function. LEVEL OF EVIDENCE: Case series with no comparison groups, Level IV.

Proprioceptive accuracy in women with early and established knee osteoarthritis and its relation to functional ability, postural control, and muscle strength.

The purpose of this study was to identify differences in knee proprioceptive accuracy between subjects with early knee osteoarthritis (OA), established knee OA, and healthy controls. Furthermore, the relation between proprioceptive accuracy on the one hand and functional ability, postural balance, and muscle strength on the other hand was also explored. New MRI-based classification criteria showing evidence of beginning joint degeneration have been used to identify subjects with early knee OA. A total of 45 women with knee OA (early OA, n = 21; established OA, n = 24) and 20 healthy female control subjects participated in the study. Proprioceptive accuracy was evaluated using the repositioning error of a knee joint position sense test using a three-dimensional motion analysis system. Subjective and objective functional ability was assessed by the knee injury and osteoarthritis outcome score, the timed "Up & Go" test, and the stair climbing test. The sensory organization test measured postural control. Muscle strength was measured by isokinetic dynamometry. Early OA subjects showed no significant differences in proprioceptive accuracy compared to healthy controls. In contrast, established OA subjects showed a higher repositioning error compared to early OA subjects (+29 %, P = 0.033) and healthy controls (+25 %, P = 0.068). Proprioceptive accuracy was not significantly associated with functional ability, postural balance, and muscle strength. Knee joint proprioceptive deficits were observed in established OA but not in early OA, suggesting that impaired proprioception is most likely a consequence of structural degeneration, rather than a risk factor in the pathogenesis of knee OA. Impaired proprioceptive accuracy was not associated with disease-related functionality in knee OA patients. Treatment strategies designed to address proprioceptive deficits may be not effective in prevention of knee OA progression and may have no impact on patients' functionality. However, this should be confirmed further in well-designed clinical trials.

Rambling and trembling in response to body loading.

Various studies have suggested that postural sway is controlled by at least two subsystems. Rambling-Trembling analysis is a widely accepted methodology to dissociate the signals generated by these two hypothetical subsystems. The core assumption of this method is based on the equilibrium point hypothesis which suggests that the central nervous system preserves upright standing by transiently shifting the center of pressure (COP) from one equilibrium point to another. The trajectory generated by this shifting is referred to as rambling and its difference from the original COP signal is referred to as trembling. In this study we showed that these two components of COP are differentially affected when standing with external loads. Using Detrended Fluctuation analysis, we compared the pattern of these two signals in different configurations of body loading. Our findings suggest that by applying an external load, the dynamics of the trembling component is altered independently of the area of postural sway and also independently of the rambling component. The dynamics of rambling changed only during the backloading condition in which the postural sway area also substantially increased. It can be suggested that during loaded standing, the trembling mechanism (which is suggested to be activated by peripheral mechanisms and reflexes) is altered without affecting the central influence on the shifts of the equilibrium point.