Thierry Conrozier

Background: Adolescent patellofemoral pain syndrome (APFS) is the most common cause of knee pain in this population. Despite its high prevalence, it remains frequently underestimated and is often considered a benign and self-limiting condition. However, persistent symptoms, significant psychosocial burden, and limited long-term efficacy of conventional treatments challenge this traditional view and call for an updated understanding of its underlying mechanisms and management. Main body: This narrative review is based on a structured literature search conducted in PubMed and Google Scholar, with studies selected according to predefined relevance criteria. APFS typically develops around puberty and predominantly affects physically active adolescents, particularly females. Clinical presentation is characterized by activity-related anterior knee pain and pain during prolonged sitting. Diagnosis remains primarily clinical, although it should incorporate assessment of biomechanical, functional, and psychosocial factors. While standard imaging is usually unremarkable, advanced magnetic resonance imaging techniques have revealed early structural and biochemical cartilage alterations. Current evidence supports a multifactorial model of pain involving both peripheral nociceptive sources and central sensitization mechanisms, further supported by neuroimaging studies. Psychosocial factors, including kinesiophobia, reduced participation in physical activity, and impaired quality of life, play a key role in symptom persistence. Standard management based on education, load management, and rehabilitation yields suboptimal outcomes in a substantial proportion of adolescents. Emerging approaches include psychologically informed interventions, digital adherence strategies, and adjunctive therapies such as intra-articular hyaluronic acid. Conclusion: APFS should no longer be regarded as a benign condition. A shift toward earlier, multimodal, and individualized management is warranted, integrating physical, psychological, and educational components. Improved understanding of central pain mechanisms and the development of adjunctive therapeutic strategies may contribute to better outcomes and prevention of chronicity.

Background: Arterial hypertension (AH) is a frequent comorbidity in patients with osteoarthritis (OA). Among antihypertensive agents, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), and beta-blockers (βBs) have been suggested to influence OA progression and symptomatology. The aim of this study was to assess whether the duration of effectiveness (DE) of viscosupplementation (VS) differs between patients with knee OA who are receiving antihypertensive treatment and those who are not. Methods: This post hoc analysis was conducted using data from a cross-sectional clinical trial (ClinicalTrials.gov Identifier: NCT04988698). The study included consecutive patients with knee OA who came for consultation at the Rheumatology Department and had received intra-articular hyaluronic acid injections within the past three years. The primary outcome was DE, self-reported by patients as the number of weeks of symptom relief. Associations between DE and various factors, including demographics, disease duration, radiographic OA severity (Kellgren–Lawrence grade and affected compartments), comorbidities, OA treatment history, antihypertensive therapy, physical activity level, and prior VS sessions, were analyzed using bivariate and multivariate models. Results: A total of 105 patients (65 women, 149 treated knees) were included. The mean age was 66.1 ± 13.2 years, and the mean body mass index (BMI) was 27.5 kg/m². Thirty-eight percent of patients were receiving antihypertensive treatment (mean number of agents: 1.9; range: 1–4), including CCBs (n = 15), ACE inhibitors (n = 13), ARBs (n = 7), βBs (n = 6), and diuretics (n = 2). The overall mean DE of VS was 48.2 ± 24.8 weeks, with a trend toward longer DE in hypertensive patients compared to non-hypertensive patients (53.1 ± 31.3 vs. 45.4 ± 19.8 weeks, p = 0.06). Bivariate analysis identified significantly longer DE in patients with BMI < 27.5 kg/m² (p = 0.002), Kellgren–Lawrence grade < 4 (p = 0.008), an active lifestyle (p = 0.005), unicompartmental OA (p = 0.01), medial tibiofemoral joint space narrowing (p = 0.046), and fewer than four prior VS sessions (p = 0.02). In multivariate analysis, AH was strongly associated with prolonged DE (p < 0.001), despite AH patients having a higher BMI (29.8 ± 5.5 vs. 25.2 ± 5.2 kg/m², p = 0.001) and being more frequently sedentary (25.5% vs. 13.8%, p = 0.07). A trend toward longer DE was observed in patients treated with βBs and ARBs but not with CCBs or ACE inhibitors. Additional independent predictors of longer DE included BMI < 27.5 kg/m² (p < 0.001), unicompartmental OA (p = 0.02), fewer than four prior VS sessions (p = 0.02), and an active lifestyle (p = 0.027). Conclusions: These findings suggest that antihypertensive treatment may extend the effectiveness of viscosupplementation in knee OA. However, the sample size was insufficient to determine whether specific classes of antihypertensive agents provide greater benefits. Further large-scale, prospective studies are warranted to clarify the potential impact of antihypertensive medications on viscosupplementation outcomes in knee OA.

Background: The clinical performance of intra-articular hyaluronic acid (HA) is strongly dependent on its resistance to oxidative degradation within the inflamed osteoarthritic joint. Reactive oxygen species induce HA chain scission, leading to a loss of molecular entanglement and a shift from elastic-dominant to viscous-dominant behavior. Tranexamic acid (TXA), a lysine analogue with documented anti-inflammatory and anti-proteolytic properties, has been combined with HA with the hypothesis that it may limit oxidative-induced rheological degradation. Objective: This study aims to determine whether an HA–TXA formulation preserves viscoelastic integrity under oxidative stress and how its behavior compares with linear, hybrid, and cross-linked HA viscosupplements. Methods: Four HA-based formulations were evaluated using stress-controlled rotational rheometry compliant with ISO 3219 standards. Complex modulus (G*), complex viscosity (η*), and phase angle (tan δ) were measured within the linear viscoelastic domain. Oxidative challenge was induced with hydrogen peroxide (5.4% v/v), and time-dependent rheological changes were recorded over 30 min. Resistance to degradation was defined by relative variations in rheological parameters from baseline. Results: Baseline measurements revealed distinct viscoelastic profiles among the HA formulations. After oxidative exposure, the HA–TXA formulation showed a modest decrease in η* (−17.0%) and limited increase in tan δ (+4.0%), indicating preserved viscoelastic organization. Its stability exceeded that of hybrid (−40%; +12.6%) and linear HA (−53%; +25.6%) and approached that of cross-linked HA (−25.4%; +5.6%). The magnitude of microstructural alteration remained minimal despite chemical stress. Conclusions: The association of TXA with HA confers a marked protection against oxidative-induced viscoelastic degradation, preserving macromolecular network integrity and elastic behavior. These findings suggest that TXA modulates oxidative stress-related rheological failure of HA through mechanisms distinct from chemical cross-linking.

Background: Viscosupplementation (VS) by intra-articular injections of hyaluronic acid (HA) is an increasingly used treatment of hip osteoarthritis (OA). However, there are no clear European recommendations for its use. Methods: Twelve members of the European Viscosupplementation Consensus Group (EUROVISCO), made up of rheumatologists, orthopedic surgeons, and rehabilitation physicians from European countries, were asked to make a therapeutic decision on 23 statements based on an exhaustive analysis of the literature and their clinical experience, using the Delphi method. For each statement, the strength of agreement and the level of consensus were calculated by the chairman of the group Results: The expert panel reached unanimous or high consensus, either for or against, on 16 of the proposed statements. The main ones are: Current evidence and the results of observational trials support the use of VS in patients with hip OA who do not require surgery. VS is more effective in cases of mild to moderate hip OA. Hip VS is safe and well tolerated, even with repeated injections. The outcome of VS depends on the viscosupplement used. A standard X-ray must be obtained before deciding on VS. VS must be performed under imaging guidance. A single injection regimen is preferable to repeat injections. VS can be considered for individuals who wish to postpone surgery. Hip replacement surgery should not be performed within 3 months of VS. VS should not be used to treat an osteoarthritis flare. VS is part of a multimodal treatment for hip OA. Conclusion: This set of recommendations is intended to help practitioners make decisions about HA VS in patients with OA.

Objective: Viscosupplementation (VS) by intra-articular injections of hyaluronic acid (HA) is a commonly used treatment of knee osteoarthritis. However, there are no clear recommendations for its use in clinical situations not usually addressed in therapeutic guidelines. Design: Members of the European Viscosupplementation Consensus Group (EUROVISCO), made up of rheumatologists, orthopedic surgeons, and rehabilitation physicians from seven European countries, were asked to make a therapeutic decision on 30 clinical scenarios based on their clinical experience and data from the literature, using the Delphi method. For each scenario, the strength of agreement and the level of consensus were calculated by the chairman of the group. Results: The expert panel reached consensus on 18 of the 30 clinical scenarios proposed. According to the experts, the factors that most influence the decision to use VS with HA to treat knee osteoarthritis are the nature and severity of symptoms, the presence of comorbidity, the absence of therapeutic alternatives, and the patient’s refusal to undergo knee arthroplasty. Obesity and an advanced radiological degree of osteoarthritis have been identified as the two main factors for poor response to VS with HA and should be considered before any decision is made to viscosupplement. Conclusion: This set of recommendations, based on common clinical scenarios, is intended to help practitioners make decisions about HA VS in patients with osteoarthritis of the knee.

Objectives: Viscosupplementation with hyaluronic acid (HA) is a commonly used intra-articular treatment for osteoarthritis (OA). We performed a Delphi consensus process to formulate guidelines for the use of intra-articular hyaluronic acid (IAHA) knee injection according to the patient’s characteristics. Methods: The EUROVISCO group consists of 12 members who had expertise in clinical and/or research in the field of OA and IAHA treatment. This group drafted issues through an iterative process and subsequently voted according to a Delphi process on their level of agreement (LoA) on these recommendations. The scores were pooled to generate a median agreement score for each recommendation. The strength of the recommendation (SOR) was classified as strong if the median agreement score was ≥8. The level of consensus (LOC) was also obtained. The level of evidence was given for each recommendation. Results: A total of 34 statements were evaluated by the expert group. A unanimous or high LoA was obtained in 16. IAHA can be considered irrespective of the age in patients with symptomatic knee OA. It can be used in patients with diabetes and/or moderate to severe obesity. It can also be used in knee OA patients with a history of gout, meniscocalcinosis and with mild-to-moderate varus/valgus malalignment. The group recommended against the use of VS in pregnant women and in OA flare. Conclusion: In summary, the working group provided strong recommendations for the use of IAHA injection that will facilitate individualized treatment decision algorithms in the management of knee OA.

Rationale: Tranexamic acid (TXA) is a strong and specific plasminogen activator inhibitor with inhibitory effects on the matrix metalloproteases involved in the pathophysiology of osteoarthritis (OA) through targeting of the fibrinolysis pathway. In this study, we evaluated the analgesic and chondroprotective effects of a HA-tranexamic acid (HA/TXA) conjugate, compared to HA alone and placebo, in an animal model of knee OA.Methods: Knee OA was induced in 15 C⁵7 b l/6J mice by IA injection of 0.75 mg of Monosodium IodoAcetate (MIA). At day 28, the mice received 1 IA injection of 10 µL of saline (control-group), or of HA or of HA/TXA. Tactile sensitivity was assessed using von Frey filaments. Stimulations started at 1 g and increased until a response was obtained (up to 4 g). A response to the stimulus was counted if the animal withdrew its paw. If the animal responded to the 1 g stimulation, stimulation was reduced until the lack of response was observed (up to 0.2 g). At day 56, mice were euthanized for knee histological assessment. Cartilage degradation was assessed using the OARSI score. Statistical analysis was performed on GraphPad Prism 8.0.2 software. Kruskal–Wallis or Mann-Whitney tests were performed as appropriate.Results: Just before treatment administration, no intergroup difference in paw withdrawal threshold was observed. Throughout the experiment animals given saline and HA had a lower paw withdrawal threshold than those treated with HA/TXA (p < 0.01). In the control group OARSI score was 5.5 ± 0.6. In HA and HA + TXA treated mice the OARSI score was 3.2 ± 0.8 and 3.1 ± 0.5 (p < 0.01) showing that both treatments were able to reduce OA progression.Conclusion: In this animal model of MIA induced KOA, a single IA injection of a HA/TXA conjugate resulted in a greater efficacy on pain than both saline and HA. HA and HA/TXA exhibited chondroprotective effects compared to placebo.

Background/Objectives: There is a gap between the very positive opinion of patients and doctors regarding knee viscosupplementation (VS) and the contrasting results of controlled studies. The objective of this study was to evaluate the overall satisfaction and predictors of satisfaction with VS in patients with knee osteoarthritis treated with VS. Methods: Post-hoc analysis of a cross-sectional study in patients with knee OA treated with one injection of a mannitol-modified cross-linked HA (HANOX-M-XL). The primary outcome was satisfaction, self-assessed semi-quantitatively by the patients. Demographics, radiological features, comorbidities, OA and comorbidities treatments, and lifestyle associated with satisfaction were studied in bivariate and multivariate analysis. Results: 89 patients (124 knees) were analyzed. A total of 88.7% were satisfied with the treatment. Satisfaction was correlated with duration of effectiveness (DoE) and negatively correlated with BMI. Satisfaction was higher in active versus sedentary patients, in tibiofemoral involvement, in Kellgren-Lawrence grade 1–3 versus 4, and in subjects not requiring intraarticular corticosteroid (IACS) concomitantly to VS. Satisfied subjects were older than dissatisfied ones. In multivariate analysis, older age, K–L grade < 4, absence of IACS, and longer DoE were associated with higher rates of satisfaction. Conclusions: We identified several predictive factors of patient satisfaction after VS of the knee. Alongside these objective factors, there are probably subjective factors linked to patient beliefs, fears, and expectations impacting satisfaction.

Background: An advanced radiological stage and obesity are predictive of poorer and shorter responses to viscosupplementation in patients with knee osteoarthritis (OA). Very little is known regarding the impact of other factors such as sport practice, comorbidities, or anatomical features of OA. Methods: This study aimed to investigate patients’ and OA characteristics associated with the duration of the effectiveness (DE) of viscosupplementation in patients with knee OA. It was a cross-sectional, single-centre clinical trial in patients with knee OA treated with intra-articular (IA) hyaluronic acid (HA) injection(s) within the previous 3 years. The investigators collected data regarding demographic and radiographic features (Kellgren–Lawrence grade and involved knee compartments), dosing regimen (single or repeat injections), the presence and volume of joint effusion, previous or concomitant IA corticosteroid injection, the number of previous viscosupplementations, and comorbidities. Patients completed a questionnaire including the self-assessment of DE (the number of weeks during which viscosupplementation was effective on symptoms), the activity level (sedentary, active, or athletic), and the level of sport activity (light, moderate, or intensive). Predictors of the DE were studied in bivariate and multivariate analyses. Results: In total, 105 patients (149 knees) were analysed (62% women, mean age 66.1 ± 13.2 years, mean BMI 27.5 ± 7.5 kg/m²). The mean DE was 48.2 ± 24.8 weeks. In bivariate analysis, the predictors of a shorter DE were BMI > 27.5 kg/m², more than three previous viscosupplementations, Kellgren–Lawrence grade 4, sedentary patients, and multicompartmental involvement. In the multivariate analysis, four independent factors remained associated with a shorter DE: BMI > 27.5 kg/m², multicompartmental knee involvement, number of viscosupplementations >3, and sedentary lifestyle. A statistically significant association between a longer DE and arterial hypertension was found, suggesting a beneficial effect of certain antihypertensive medications. Conclusions: This study confirms that being overweight significantly reduces the duration of the effectiveness of viscosupplementation. It also shows that viscosupplementation is more lastingly effective in unicompartmental OA and among active or athletic patients. The duration of effectiveness decreases when the treatment is repeated more than three times.

BackgroundAdvanced radiological stage of knee osteoarthritis (OA) and obesity are predictive of poorer and shorter response to viscosupplementation, but very few is known regarding the impact of other factors such as sport practice, comorbidities or anatomical features of OA. ObjectivesTo investigate the patient’s and OA characteristics associated with the duration of effectiveness (DE) of viscosupplementation in patients with knee OA.MethodsCross-sectional single center trial in patients with knee OA treated with intra-articular (IA) hyaluronic acid (HA) injection(s) within the previous 3 years. The investigator collected demographic and radiographic data (Kellgren grade, involved knee compartments), dosing regimen (single or repeat injections), presence and volume of joint effusion, previous or concomitant IA corticosteroid injection, number of previous viscosupplémentations and the comorbidities. The patient completed a questionnaire including the self-assessment of DE (number of weeks during which viscosupplementation was effective on symptoms), the activity level (sedentary, active, athletic), the level of sport activity (light, moderate or intensive). Predictors of DE were studied in univariate and multivariate analyses ResultsOne hundred five patients (149 knees) were analyzed (62% women, mean age 66.1 ± 13.2 years, mean BMI 27.5 ± 7.5 kg/m²). The mean DE was 48.2 + 24.8 weeks. In a bivariate analysis, the predictors of a shorter with DE were BMI >27.5kg/m2, more than 3 previous viscosupplémentations, Kellgren grade 4, sedentary patients, and more than 1 affected compartment. In the multivariate analysis, 4 independent factors remained associated with a shorter DE: BMI >27.5 kg/m2, knee multi-compartment damage, number of viscosupplements >3, sedentary lifestyle. A statistically significant association between a longer DE and treated arterial hypertension was found suggesting a beneficial effect of certain antihypertensive drugs. ConclusionThe study confirms the harmful influence of an increased BMI, It also shows that viscosupplementation is more effective in unicompartmental OA. Other points worth highlighting are the reduction in the duration of efficacy with repeated cycles of injections and the benefit of a regular physical activity.