Correlating the efficacy of knee viscosupplementation with osteoarthritic changes on roentgenological examination

doi:10.1016/S0968-0160(02)00040-6

The Knee

Volume 9, Issue 4, December 2002, Pages 321-330

https://doi.org/10.1016/S0968-0160(02)00040-6 Get rights and content

Abstract

This study was designed to identify the roentgenological changes of the knee that correlated with an unfavourable outcome when treated with an intra-articular knee viscoelastic supplementation. A prospective cohort of 60 patients receiving a standard course of intra-articular knee viscoelastic supplementation with a commercial uncross-linked hyaluronic acid derivative of an intermediate molecular weight were studied. Follow up was for 12 weeks post-treatment with clinical improvement measured using the Western Ontario and McMasters Universities Osteoarthritis Index. X-Rays of the relevant knee were viewed and graded for the severity of joint space, osteophyte, tibial spine, sclerosis, cyst formation, alignment and general severity by an observer blinded to the outcome of the treatment. There were no appreciable differences noted in the age, sex, length of follow up, pre-treatment, the severity of symptoms before treatment and number of intra-articular injections given per course in each X-ray category identified. There was a significant amount of improvement in patients with a minor loss of medial and lateral joint space in all outcome measures. Minimal changes in tibial spine and global appearance also indicated a positive outcome in stiffness, pain and overall improvement. Thus, patients with moderate to severe osteoarthritic changes in joint space on roentgenological examination would not significantly benefit from intra-articular knee viscoelastic supplementation. In addition, we feel that changes in the tibial spine and global appearance are not reviewed consistently enough to be included as part of our recommendation. As such, we conclude that only patients with a minimal to mild loss in joint space on roentgenological examination should form part of the target group who are likely to benefit from intra-articular knee viscoelastic supplementation.

Introduction

The loss of normal function with symptoms of pain and stiffness of the knee attributed to osteoarthritis is increasing in parallel with the increasing age of the general population [1], [2], [3]. Unfortunately, osteoarthritis is a progressive disease resulting in the erosion of articular cartilage [4]. These changes can be noted on roentgenological examination of the knee, which includes the reduction of joint space, subchondral sclerosis, loss of normal alignment, cyst and osteophyte formation [5], [6], [7], [8]. Consequently, the breakdown of homeostatic mechanisms protecting the joint normally provided by healthy synovial fluid results [9]. The synovial fluid from the affected joint is noted to have a decreased amount of elasticity and viscosity due to a reduction in the molecular size and concentration of hyaluronic acid [10].

Whilst various treatments such as simple analgesia, non-steroidal anti-inflammatory drugs (NSAIDs), weight loss, as well physical therapy, are advocated in the conservative management of osteoarthritis [11], the improvement in function is thought to be attributed to a better management of nociception [12]. A further method of treating osteoarthritis is thought to be intra-articular injections of highly elastoviscous solutions of hyaluronic acid derivatives (HADs). The aim of this treatment is to restore the rheological properties of healthy synovial fluid [13], [14]. HADs are thought to act by scavenging free radicals [14], promote the normalisation of hyaluronic acid synthesis [15], as well as to help maintain the structural and functional characteristics of cartilage cells [16], [17]. The improved the lubrication properties of the synovial fluid decreases the sensation of pain and discomfort which then allows an increased range of movement [10].

Intra-articular knee injections of various HADs have both been shown to improve the functional and symptomatic outcome in various studies [18], [19], [20], [21], [22], [23], [24], [25], [26] when compared to conventional therapy or placebo. Current indications for HAD therapy currently include patients still using the affected joint actively with symptoms of joint pain. It is also thought to be effective in any stage of joint pathology [14]. However, many recipients of this treatment have reported no change in their symptoms and have occasionally reported a detrimental outcome [27].

We feel that the amount of benefit from viscosupplementation in the knee is related the severity of joint osteoarthritis. In this study, we aim to correlate the efficacy of viscosupplementation with the severity of osteoarthritis on roentgenological examination. This method of classifying severity was chosen as it is a standardised way of classifying the initial severity of osteoarthritis. It can also be blinded to the outcome of treatment and is not confounded by the individual patient perception of pain. A significant correlation will enable us to target specific groups that are likely to benefit from this form of intervention.

Section snippets

Method

Patients selected for this study were of a prospective cohort of patients with clinical osteoarthritis of the knee, unresolved with symptomatic treatment, but not severe enough to warrant surgical intervention. A total of 60 patients were included into the study with one withdrawn due to an adverse gastrointestinal reaction to the initial injection.

Each patient had a standard course of three intra-articular 2-ml injections of viscoelastic supplementation with a commercial uncross-linked

Result

The 60 patients in this study treated with Orthovisc^® did not show any significant differences in the age, length of follow up and initial scores between the two patient groups compared to its final outcome. In addition, the distribution of knee osteoarthritic changes were not noted to be significantly related to the initial symptom scores.

The relationship between the severity of global osteoarthritic change and amount of improvement following treatment can be seen in Fig. 1. It is noted that a

Discussion

In current clinical practice, knee viscosupplementation is generally indicated in patients with symptoms of joint pain due to osteoarthritis [13]. This has been shown to be at least as effective as NSAID therapy in various studies, without the associated side effects [11]. Unfortunately, up to 50% of subjects did not respond to viscosupplementation in various studies [18], [19], [20], [21], [22], [23], [24], [25], [26]. This is mirrored in our study where 35% of patients reported either an

Conclusion

Based on this limited study, we conclude that patients with a moderate to severe loss in joint space of the knee with clinical symptoms of osteoarthritis are unlikely to benefit from treatment and should not be offered viscosupplementation. In addition, despite evidence that patients with minimal changes in the tibial spine and global osteoarthritis report a significant improvement in terms of pain and stiffness, the use of these roentgenological criteria can be unreliable.

Whilst there were no

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Cited by (28)

Consensus statement on viscosupplementation with hyaluronic acid for the management of osteoarthritis
2015, Seminars in Arthritis and Rheumatism
Citation Excerpt :
Average = 8.1; SD = 1.8; median = 8.5; range: 8–10. To date, very few articles have been focused on the predictive factors of response or failure of VS. The only predictive factor of poor response that has been regularly reported in the literature is the advanced stage of the disease [36,47,49,95–97]. Some biomarkers such as serum hyaluronic acid concentrations and urinary C-telopeptide fragments of type II collagen [63] were suggested to be of prognostic value, but none of them has been proven to be useful at an individual level to predict either OA progression or the efficacy of VS. The experts insisted on the absolute necessity of conducting research specifically designed to accurately determine the factors influencing treatment outcome.
Viscosupplementation (VS) with hyaluronic acid is currently used by physicians to treat osteoarthritis. However, many aspects of this treatment remain questionable and subject of controversy. A group of 8 experts in this field, from European countries, met to debate on 24 statements previously listed by the group members. Based on an extensive research of the literature and expert opinion, a consensus position has been proposed for each statement. Agreement was achieved on some recommendations. In particular, the expert achieved unanimous agreement in favor of the following statements: VS is an effective treatment for mild to moderate knee OA; VS is not an alternative to surgery in advanced hip OA; VS is a well-tolerated treatment of knee and other joints OA; VS should not be used only in patients who have failed to respond adequately to analgesics and NSAIDs; VS is a “positive” indication but not a “lack of anything better” indication; the dosing regimen must be supported by evidence-based medicine; cross-linking is a proven means for prolonging IA residence time of HA; the best approach to inject accurately knee joint is the lateral mid-patellar one; when VS is performed under fluoroscopy, the amount of radiopaque contrast agent must be as low as possible to avoid viscosupplement dilution. These clear recommendations have been established to help practitioners in the use of viscosupplementation.
Efficacy of Hylan G-F 20 and Sodium Hyaluronate in the treatment of osteoarthritis of the knee - A prospective randomized clinical trial
2008, Knee
Citation Excerpt :
The impact of age and radiological degree of osteoarthritis in the clinical efficacy is unclear. Some studies suggest that patients older than 65 years and with those of advanced radiographic stage arthritis were less likely to benefit from intra articular injection of HA [10,50]. However there are other studies which suggest the contrary in favour of older population with more severe knee disease as these patients may be more sensitive in detecting an analgesic effect [49,51].
In this independent prospective randomized trial, we compared the clinical effectiveness, functional outcome and patient satisfaction following intra articular injection with two viscosupplementation agents — Hylan G-F-20 (n = 199) and Sodium Hyaluronate (n = 193) in patients with osteoarthritis (OA) of the knee. All patients were prospectively reviewed by blinded independent assessors at pre injection, 6 weeks, 3, 6, 12 months. Knee pain and patient satisfaction were measured on a visual analogue scale. Functional outcome was assessed using WOMAC, Oxford knee score and EuroQol EQ-5D scores. Knee pain on VAS improved from 6.7 to 3.2 by 6 weeks (p = 0.02) and was sustained until 12 months (3.7, p = 0.04) with Hylan G-F 20. In the Sodium Hyaluronate group, pain improved from 6.6 to 5.7 at 6 weeks (p > 0.05) and to 4.1 at 3 months (p = 0.04) but was sustained only until 6 months (5.9, p > 0.05). Improvement in the WOMAC pain subscale was significantly superior in the Hylan G-F 20 group at 3 months (p = 0.02), 6 months (p = 0.01) and 12 months (p = 0.007). There was no significant difference in the EQ-5D scores at 6 weeks and 3 months between the two groups. The numbers of treatment related adverse events were higher (39 vs. 30) in the Hylan G-F 20 group. One patient in the Hylan G-F 20 group who had a serious adverse event was also included in the final analysis. Although both treatments offered significant pain reduction, it was achieved earlier and sustained for a longer period with Hylan G-F 20. From this study, it appeared that the clinical effectiveness and general patient satisfaction are better amongst patients who received Hylan G-F 20.
Injection of intra-articular sodium hyaluronidate (Sinovial®) into the carpometacarpal joint of the thumb (CMC1) in osteoarthritis. A prospective evaluation of efficacy
2007, Joint Bone Spine
Citation Excerpt :
Such a difference is not seen in group 1. However, it is important to note that most radiological severe cases were in group 1, even if not statistically significant; furthermore, clinical response is probably dependent on the radiological lesions, as shown by Toh in the knee [14]. One month after injection (baseline) with a shorter delay between injection and evaluation in group 3 is a possible reason of stronger response at one month in this group.
To compare the efficacy on pain relief and function of one, two or three injections of intra-articular hyaluronic acid in symptomatic osteoarthritis (OA) of the carpometacarpal joint of the thumb (CMCJ).
Among subjects with symptomatic OA of the CMCJ of the thumb referred to the Rheumatology Department of Nice, patients free of any joint injection in last 6 months with pain visual analogue score (VAS) >40 and with Kellgren and Lawrence score between 2 and 4 were included. Each subject was randomly allocated to receive, at weekly intervals, 1 (group 1) or 2 (group 2) or 3 injections (group 3) of 1 ml Sodium Hyaluronidate (Sinovial^®). Injections were given under imaging control. Sociodemographic characteristics, VAS and functionality (Dreiser Functional Index) were assessed at baseline, at one month and at three months. An intention to treat analysis was performed.
Forty two subjects were enrolled in the study. Their mean age was 64.8 (8.0) years, and 90.5% were women. Baseline pain VAS, and mean Dreiser functional index were respectively 57.7 (17.1) and 12.5 (5.8). A repeated measure analysis of variance (ANOVA) model was used to compare the time-course profile of the three treatment groups for VAS and Dreiser index. Due to statistically significant groups-time interaction the analyses were conducted at each evaluation time. No difference was found for VAS at 1 month (p = 0.075) and 3 months (p = 0.382). Intra group differences between baseline and three months was significant in groups 2 and 3 (p = 0.012 and p = 0.002).
No significant differences were found between each group over the study period for pain relief and function. But the intra groups analysis results show that intra-articular sodium hyaluronidate injections into the carpometacarpal joint of the thumb in osteoarthritis can be efficacious on pain and fuctionality. What is now needed is a controlled placebo randomised study with larger samples and longer term follow up of the achieved effects.
Injection of intra-articular sodium hyaluronidate into the carpometacarpal joint of the thumb (CMC1) in osteoarthritis. A prospective evaluation of efficacy{lozenge, open}{lozenge, open}Pour citer cet article, utiliser ce titre en anglais et sa référence dans le même volume de Joint Bone Spine.
2007, Revue du Rhumatisme (Edition Francaise)
Comparer l'efficacité, en termes de douleur et de fonction d'une, deux ou trois infiltrations d'acide hyaluronique dans la rhizarthrose symptomatique.
Ont été inclus des patients souffrant d'une rhizarthrose du pouce symptomatique, consultant dans le service de rhumatologie du CHU de Nice et répondant aux critères suivants : pas d'infiltration locale au cours des six mois précédents, échelle visuelle analogique (EVA) de la douleur supérieure à 40/100, score radiologique de Kellgren et Lawrence 2 à 4. Les patients ont été randomisés entre trois groupes de traitement par infiltration radioguidée de 1 ml d'acide hyaluronique (Sinovial^®) selon le nombre d'infiltrations effectuées à une semaine d'intervalle : une (groupe 1), deux (groupe 2) ou trois infiltrations (groupe 3). Les données sociodémographiques, l'évaluation de la douleur par EVA et l'évaluation de la fonction (index fonctionnel de Dreiser) ont été recueillies avant traitement, à un et trois mois. L'analyse des résultats a été réalisée en intention de traitement.
Parmi les 42 patients inclus dans cette étude, l'âge moyen était de 64,8 ± 8,0 ans et 90,5 % étaient de sexe féminin. Avant traitement, l'EVA de la douleur et l'index fonctionnel de Dreiser étaient respectivement de 57,7 ± 17,1 et de 12,5 ± 5,8. Un modèle d'analyses répétées de variance de type Anova a été utilisé pour comparer le profil évolutif de l'EVA-douleur et de l'index de Dreiser entre les trois groupes thérapeutiques. Du fait d'interactions statistiquement significatives entre les groupes, les analyses ont été réalisées à chaque temps d'évaluation. Il n'a pas été trouvé de différence de l'EVA-douleur à un mois (p = 0,075) et à trois mois (p = 0,382). Les différences au sein de chaque groupe, entre l'évaluation initiale et l'évaluation à trois mois, étaient significatives pour les groupes 2 (p = 0,012) et 3 (p = 0,002).
Nous n'avons pas trouvé de différence d'efficacité sur la douleur et la fonction entre les groupes thérapeutiques au cours de la période de l'étude. Mais l'analyse intragroupe montre que l'injection intra-articulaire d'acide hyaluronique peut entraîner une amélioration de la douleur et de la fonction dans la rhizarthrose. Cela doit être confirmé par une étude randomisée contre placebo, effectuée sur un plus large effectif de patients et comportant un suivi plus prolongé.
Clinical response to intra-articular injections of hylan G-F 20 in symptomatic hip osteoarthritis: the OMERACT-OARSI criteria applied to the results of a pilot study
2006, Joint Bone Spine
Citation Excerpt :
At the end of the study, approximately 40% of patients reported walking pain levels of ≤ 20 mm on VAS (mostly those patients requiring only a single injection). The outcomes appear better in less severe OA, as has already been reported in studies in knee OA [31,32], as an inverse correlation was noted between the reduction in pain and the joint space narrowing score. In an open, prospective trial Brocq et al. [15] studied 22 patients with hip OA, treated with one or two intra-articular injections of hylan G-F 20 under fluoroscopy.
To assess, using the OMERACT-OARSI criteria, the clinical response of patients presenting with symptomatic hip osteoarthritis (OA) to one intra-articular injection of hylan G-F 20.
Open-label, multi-centre, prospective, pilot study. Fifty-six patients presenting with primary hip OA, Kellgren–Lawrence grade II–III, age ≥ 40, with walking pain measuring 50–90 mm on a 100 mm visual analogue scale (VAS). Intra-articular injection of a single 2 ml dose of hylan G-F 20 into the hip joint under fluoroscopic guidance. A second injection could be administered at day (D) 30, 60 or 90 if pain was unchanged or returned to baseline levels.
The outcome of the first injection in the intent-to-treat (ITT) population was analysed 90 days after the injection in those patients that received a single injection, and on the day of the second injection in those patients that required two injections, using OMERACT-OARSI responder criteria (obtained from WOMAC A and C indices and the patient's global evaluation) and variation in walking pain on VAS.
The percentage of responders according to the OMERACT-OARSI response criteria was 53.6%. An inverse correlation was observed between reduction in pain and joint space narrowing score (P = 0.03).
In the absence of a control group, the efficacy of the treatment cannot be determined conclusively. Nevertheless these data suggest that hylan G-F 20 is a symptomatic treatment of hip OA, particularly in less severe radiological cases. A double-blind, controlled study is required to confirm these data.
Clinical response to intra-articular injections of hylan G-F 20 in symptomatic hip osteoarthritis: The OMERACT-OARSI criteria applied to the results of a pilot study{lozenge, open}{lozenge, open}Pour citer cet article, utiliser ce titre en anglais et sa référence dans le même volume de Joint Bone Spine.
2006, Revue du Rhumatisme (Edition Francaise)
Évaluer à l'aide des critères de l'OMERACT-OARSI, la réponse clinique à une injection intra-articulaire d'hylane G-F 20 chez des patients présentant une coxarthrose symptomatique.
Essai pilote prospectif multicentrique ouvert. Cinquante-six patients présentant une coxarthrose primitive, stades II–III de Kellgren-Lawrence, âgés d'au moins 40 ans, ayant une douleur à la marche chiffrée entre 50 et 90 mm sur une échelle visuelle analogique (EVA) de 100 mm. Injection intra-articulaire sous fluoroscopie, d'une dose unique de 2 ml d'hylane G-F 20, dans la hanche. Une seconde injection était réalisée au jour 30, 60 ou 90, si la douleur était toujours identique ou revenue au niveau de la douleur initiale.
Résultat de la première injection analysé en intention de traiter 90 jours après l'injection pour les patients n'ayant reçu qu'une seule injection et le jour de la seconde injection chez ceux en ayant nécessité deux. Critères de réponse OMERACT-OARSI (obtenus à partir des indices A et C de WOMAC et de l'évaluation globale du patient) et variation de la douleur à la marche sur l'EVA.
Le pourcentage de répondeurs selon les critères de l'OMERACT-OARSI était de 53,4 %. Une corrélation inverse a été observée entre la diminution de la douleur et le score de pincement de l'interligne articulaire (p = 0,03).
En l'absence de groupe témoin, l'efficacité du traitement ne peut être établie de manière concluante. Les données obtenues suggèrent néanmoins que l'hylane G-F 20 est un traitement symptomatique de la coxarthrose, en particulier dans les formes radiologiquement peu sévères. Ces résultats doivent être confirmés par une étude contrôlée en double insu.

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Correlating the efficacy of knee viscosupplementation with osteoarthritic changes on roentgenological examination

Abstract

Introduction

Section snippets

Method

Result

Discussion

Conclusion

Arch Phys Med Rehab

Radiat Phys Chem

Osteoarthr Cartilage

Osteoarthr Cartilage

Epidemiology of musculoskeletal impairments and associated disability

Am J Public Health

Osteoarthritis prevalence in the population and relationship between symptoms and X-ray changes

Ann Rheumatol Dis

Osteoarthritis in older adults

J Am Geriatric Soc

Primer on the rheumatologic diseases

Radiographic grading for knee osteoarthritis. A revised scheme that relates to alignment and deformity

J Rheumatol

Radiological assessment of osteoarthrosis

Ann Rheumatol Dis

Atlas of standard radiographs: the epidemiology of chronic rheumatism

Updated osteoarthritis reference standard

J Rheumatol

Hyaluronic acid in synovial fluid. Molecular parameters of hyaluronic acid in normal and arthritic human synovial fluid

Arthritis Rheumatism

The role of viscosupplementation with hylan GF-20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicentre trial comparing GF-20 alone, hylan GF-20 with nonsteroidal antiinflammatory drugs (NSAIDs) and NSAIDs alone

Osteoarthr Cartilage