Intra-articular Hyaluronan Research Articles

Improvement of Muscle Strength in Osteoarthritic Knee Patients After Intraarticular Knee Injection of Hyaluronan

The objective of this study was to investigate whether the knee concentric and eccentric muscle strengths can be improved in patients with bilateral knee osteoarthritis after intraarticular hyaluronan injections. A total of 25 patients with bilateral knee osteoarthritis and with a radiographic Ahlbäck grading scale of I or II participated in this study. One session of intraarticular knee injection of hyaluronan was given to both knees (weekly intraarticular knee hyaluronan injections for a total of 5 wks). Knee concentric and eccentric muscle strengths were recorded between 10 and 90 degrees of knee flexion. The recordings were done on two angular velocities, 80 and 240 degrees/sec. This study took place in a tertiary medical center with a gait laboratory and a KIN-COM isokinetic dynamometer. An increase in concentric and eccentric muscle strength adjusted for body weight (P < 0.01) was observed in both knees, ranging between 5.1% and 27.7%. The decreased knee muscle contraction strength (concentric and eccentric) can be improved in knee osteoarthritis patients with an Ahlbäck grading scale of I or II after five weekly intraarticular knee injections of hyaluronan.

The safety and efficacy of intraarticular hyaluronan with/without corticosteroid in knee osteoarthritis: 1-year, single-blind, randomized study

The goal of this study was to assess the safety and efficacy of hyaluronan (HA) with/without corticosteroid in patients with knee osteoarthritis (OA). In a 1-year, randomized, single-blind trial, 24 patients were treated with HA weekly for 3 weeks, then three injections on the 6th month for a total of six injections. Sixteen patients were treated the same but with the addition of 1 ml triamcinolone acetonide prior to the first and fourth HA injection. The treatment was repeated at the sixth month. The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the visual analog pain scale (VAS). After 1 year, progression of OA was evaluated with magnetic resonance imaging (MRI). During the study, pain relief was marked in patients who received combined treatment with respect to WOMAC pain and VAS (p<0.05). At the first year, no progression was observed in either treatment group. Although all patients had improvement for both pain and function, HA together with corticosteroid was superior to HA alone for early pain relief. The MRI findings showed that neither treatment showed a progression on the damage of the cartilage.

Hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease-modifying activity

Although available nonsurgical pharmacotherapies for treatment of osteoarthritis (OA) are considered to be solely symptom-modifying agents, recent advances have been made in the search for agents that may modify disease progression. Intra-articular hyaluronan (HA) therapy is one symptom-modifying approach that has been found to be safe and effective for reducing pain due to OA of the knee. Presented here is a review of the evidence that HAs may also modify the rate of OA disease progression in addition to providing symptomatic efficacy. A review of the literature based on a MEDLINE search through June 2004, using the terms HA, sodium hyaluronate, hyaluronic acid, hylan, hylan G-F 20, OA, disease modification, structure modifying and joint structure. Evidence for disease-modifying activity of HAs stems from 1) the complex biochemical effects of HAs in the synovium and extracellular matrix of the articular cartilage, including interactions between exogenously administered HA and articular cartilage, subchondral bone, matrix proteoglycans, and collagens; 2) the effects of HA administration in animal models of OA, including total or partial meniscectomy and anterior cruciate ligament transectomy; 3) results of clinical trials using one HA, Hyalgan (sodium hyaluronate, molecular weight 500-730 kDa) that evaluated structural outcomes, such as joint-space width, chondrocyte density and vitality, and arthroscopic evaluation of chondropathy. Growing preclinical and clinical evidence supports the notion that, in addition to relieving the symptoms of OA, HAs also modify the structure of the diseased joint and the rate of OA disease progression, at least early in the evolution of the disease process.

Filtration rate dependence of hyaluronan reflection by joint-to-lymph barrier: evidence for concentration polarisation.

Hyaluronan (HA), a component of synovial fluid, buffers fluid loss from joints. To explain this, a quantitative theory for HA concentration polarisation at a partially sieving synovial lining was developed. The theory predicts a fall in HA reflected fraction R with increased filtration rate. To test this, knees of anaesthetised rabbits were infused with HA and fluorescein-dextran (FD) at constant trans-synovial filtration rates of 6-89 microl min(-1). Samples of femoral lymph, mixed intra-articular fluid and subsynovial fluid after >/= 3 h were analysed by high-performance liquid chromatography. R was calculated as (1 - downstream/upstream concentration), using [FD] to adjust for joint lymph dilution in femoral lymph. Intra-articular HA concentration after >/= 3 h, 0.47 +/- 0.02 mg ml(-1) (mean +/-s.e.m., n= 31), exceeded the infusate concentration, 0.20 mg ml(-1), while subsynovial and lymph [HA] were reduced relative to [FD]. The changes in [HA] demonstrated synovial molecular sieving of HA. R from cavity to lymph (R(lymph)) fell monotonically from 0.93 at 6 microl min(-1) to 0.14 at 89 microl min(-1) (P < 0.0001, regression analysis, n= 33). R values calculated from the intra-articular HA accumulation (R(asp)) or the low subsynovial concentrations (R(syn)) were similar negative functions of filtration rate. R for lymphatic capillary endothelium (R(endo)), calculated from lymph/subsynovial concentration ratios, was effectively zero (-0.03 +/- 0.18, n= 21), confirming that synovium, not initial lymphatic endothelium, is the reflection site. Logarithmic linearisation of the results evaluated the synovial HA reflection coefficient as 0.91. In conclusion, the existence of concentration polarisation during joint fluid drainage was supported by the demonstration of a negative relation between filtration rate and R(lymph), R(asp) and R(syn).

Changes in sagittal ground reaction forces after intra-articular hyaluronate injections for knee osteoarthritis

Tang SF, Chen CP, Chen MJ, Pei Y-C, Lau Y-C, Leong C-P. Changes in sagittal ground reaction forces after intra-articular hyaluronate injections for knee osteoarthritis. Arch Phys Med Rehabil 2004;85:951–5. Objectives To examine the gait patterns and the sagittal ground reaction forces (GRFs) in persons with knee osteoarthritis (OA) after intra-articular injection of hyaluronate and to investigate the duration of its treatment effectiveness. Design Case-comparison study. Setting Gait laboratory in a tertiary care center. Participants Fifteen subjects (30 knees) with symptomatic knee OA (stage I or II, according to the Ahlbäck grading system), and 15 age-, mass-, and gender-matched non-OA control subjects (30 knees). Intervention After initial gait analysis, the group with knee OA received 5 weekly intra-articular injections of hyaluronate to bilateral knees. Gait analysis was performed again for the group with knee OA after the completion of hyaluronate injections. Main outcome measures Forceplate sagittal GRFs and gait parameters of velocity, cadence, step length, and stride time. Results The distinctive 2-peak force vector GRF was lost in persons with knee OA. The first peak rise time was significantly delayed ( P<.05). The group with knee OA also revealed slower walking velocity and cadence, as well as longer stride time, than the control group ( P<.05). The distinctive 2-peak force vector GRF diagram could be recovered in patients with knee OA after the completion of hyaluronate injections. Conclusions Gait patterns and GRFs improved significantly after intra-articular knee injection of hyaluronate in persons with Ahlbäck stages I and II knee OA. The clinical treatment effect was immediate and may last for 6 months or more.

Management Strategies for Osteoarthritis, Ankylosing Spondylitis, and Gouty Arthritis

Rheumatic diseases are among the most frequent causes of pain and disability. Effective management of rheumatic diseases including osteoarthritis (OA), ankylosing spondylitis (AS), and gouty arthritis requires an understanding of the underlying disease mechanisms.Symptoms of OA result from both mechanical factors and elements of inflammation. Current management strategies target both of these factors and generally consist of nonpharmacologic and pharmacologic interventions, including use of nonspecific nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase-2-specific inhibitors (coxibs), which have analgesic and antiinflammatory properties. Other approaches include intraarticular hyaluronate and the use of alternative therapies under investigation such as acupuncture or glucosamine.Disease mechanisms in AS involve enthesitis, an inflammation at the site of insertion of ligaments, tendons, or joint capsules to bone. Posture and exercise are important nonpharmacologic strategies that may be made easier with the use of NSAIDs or coxibs. Recently developed therapies, including tumor necrosis factor inhibitors, target the underlying disease mechanisms and have demonstrated dramatic symptomatic effects. Disease-modifying effects still need to be established.In gout, hyperuricemia leads to crystal-induced inflammation in some patients. Etoricoxib, one of the newer coxibs, has shown promise in treating acute gout, with efficacy similar to indomethacin, the current standard NSAID often used in these patients. Oral or intraarticular steroids can also be considered. For chronic care uricosurics can be beneficial if renal function is normal and excretion is not excessive, but allopurinol is used most often. Nonpharmacologic modalities, such as rest and cold applications, are useful for acute episodes, and lifestyle modification in the form of diet can also play a role in chronic disease management.

Synovial response to intraarticular injections of hyaluronate in frozen shoulder: a quantitative assessment with dynamic magnetic resonance imaging

AbstractTo clarify the response of frozen shoulder (FS) to intraarticular injections of high-molecular-weight sodium hyaluronate (HA), a mixture of 2.5 ml of HA and 1.5ml of 1% lidocaine was injected into the glenohumeral joint of 11 patients with FS, 8 of whom received five weekly injections. The patients were assessed using the Japanese Orthopaedic Association shoulder score (JOA score) before the first injection, 1 week after the first injection, and 1 week after the final injection. Following each clinical evaluation, the patients underwent dynamic magnetic resonance imaging enhanced with Gd-DTPA, and the coefficient of enhancement (CE) in the glenohumeral synovium was calculated, with the examiners blinded to the clinical information. The JOA score tended to be greater and the CE smaller after injection than before injection. The changes in the CE following both single and repeated injections were negatively correlated with changes in the JOA score. Thus, clinical improvement in patients with FS was associated with a decrease in the CE. Because the CE depends on the degree of synovitis, the therapeutic effect of intraarticular HA injection for FS results, at least in part, from suppression of synovitis in the glenohumeral joint through an antiinflammatory effect.

Hyaluronate inhibits the interleukin-1beta-induced expression of matrix metalloproteinase (MMP)-1 and MMP-3 in human synovial cells.

Intra-articular administration of hyaluronate (HA) is an effective treatment for arthritis. HA injections can decrease not only joint pain but also synovial effusion, although little is known concerning the mechanism of HA action. The aim of this study was to investigate the role of HA on the expression and production of matrix metalloproteinase (MMP) in synovial cells activated by interleukin (IL)-1beta in order to achieve a better understanding of exogenous HA function in the extracellular matrix degradation in arthritic joints. Human synovial cells were incubated with HA (0.1-1000 microg/ml) and/or IL-1beta (1 ng/ml). The expression of MMP-1 and MMP-3 mRNAs was analyzed by quantitative real-time polymerase chain reaction. The protein levels of MMP-1 and MMP-3 in cultured media were measured by immunoblotting. Expression of MMP-1 and MMP-3 mRNAs was induced by IL-1beta. The IL-1beta-mediated induction of MMP-1 mRNA expression was attenuated by 10 microg/ml HA (p=0.026) and that of MMP-3 mRNA was strongly down-regulated in the presence of 10 or 1000 microg/ml HA (p<0.001). The increased protein levels of MMP-1 and MMP-3 were also reduced by 1000 microg/ml HA. These data suggest that HA inhibits the expression and production of MMP-1 and MMP-3 in IL-1beta-stimulated human synovial cells. We therefore prepose that intra-articular HA may rescue inflamed joints from bone and cartilage destruction by reducing the production of MMP-1 and MMP-3.

Synovite granulomateuse après injection de hylane GF-20. À propos de deux cas

Intra-articular hyaluronan injections are used to treat osteo-arthritis of the knee. Acute painful swelling with a joint effusion develops locally after the injection in about 10% of cases but resolves spontaneously. Crystals are identifiable in some patients, but the mechanism in crystal-negative cases remains unknown. We report knee arthritis with inflammatory joint fluid free of organisms and crystals in two patients after Hylan GF-20 treatment for femorotibial osteo-arthritis. Synovial membrane histology disclosed granulomatous synovitis with epithelioid histiocytic and multinucleate giant cells but no visible foreign bodies. These two cases suggest that crystal-negative arthritis after Hylan GF-20 injection may be ascribable to granulomatous synovitis of the foreign-body giant-cell type.

Granulomatous synovitis after intraarticular Hylan GF-20. A report of two cases

Intraarticular hyaluronan injections are used to treat osteoarthritis of the knee. Acute painful swelling with a joint effusion develops locally after the injection in about 10% of cases but resolves spontaneously. Crystals are identifiable in some patients, but the mechanism in crystal-negative cases remains unknown. We report knee arthritis with inflammatory joint fluid free of organisms and crystals in two patients after Hylan GF-20 treatment for femorotibial osteoarthritis. Synovial membrane histology disclosed granulomatous synovitis with epithelioid histiocytic and multinucleate giant cells but no visible foreign bodies. These two cases suggest that crystal-negative arthritis after Hylan GF-20 injection may be ascribable to granulomatous synovitis of the foreign-body giant-cell type.

Long-term effect of sodium hyaluronate (Hyalgan ®) on osteoarthritis progression in a rabbit model

Background: Intra-articular (IA) hyaluronan (HA) injections are approved for the treatment of knee osteoarthritis (OA) pain. One of the currently available products is approved for repeat treatment courses. While HA is classed as a symptom-modifying agent, there is substantial evidence that this therapeutic modality also possesses disease-modifying activity. Objective: A rabbit model of OA, anterior cruciate ligament transection (ACLT), was used to investigate the long-term effects of single and sequential courses of HA therapy on OA progression. Design: One or two courses of five weekly IA injections of sodium hyaluronate (Hyalgan ®) average molecular weight, MW, of 500–730 kDa, or vehicle were administered to rabbits ( N=10 per group), initiated 4 and 13 weeks (for groups that received a second course) after ACLT. Gross morphological and histomorphometric evaluations were performed on harvested knee joints following sacrifice at 26 weeks after surgery. Results: All the rabbits exhibited the characteristic pathologic changes of OA. Rabbits that received one or two courses of HA injections showed less disease progression than rabbits treated with ACLT alone or with 10 vehicle injections. However, rabbits that received five vehicle injections also showed improved morphology compared with those given no injections. Rabbits that received 10 HA injections showed significantly less surface roughness of the femoral cartilage compared with rabbits treated with ACLT, 5 HA injections, or 10 vehicle injections, and showed significantly less surface roughness of the tibial plateau compared with all other treatment groups ( P<0.05). Conclusions: Repeat courses of HA injections reduced the degree of articular degeneration in a rabbit ACLT model of OA. Sequential courses of HA therapy may be advantageous in the long-term management of OA.

Intra-articular hyaluronans: A review of product-specific safety profiles

Background and Objectives: Intra-articular (IA) hyaluronans (HAs) are indicated for pain relief of osteoarthritis (OA) of the knee. Hyalgan (sodium hyaluronate), Supartz (sodium hyaluronate), and Synvisc (hylan G-F 20) are Food and Drug Administration-approved HA products. They are derived from rooster combs; Hyalgan and Supartz are naturally derived (unmodified); Synvisc is chemically modified to increase its molecular weight. This article reviews and updates the safety data for IA HAs used for the treatment of knee OA. Methods: References were taken from Medline through July 2002; respective product information services and information from the searchable United States Food and Drug Administration Manufacturer and User Facility Device Experience Database also were used. Results: All products demonstrated favorable safety profiles in clinical trials and practice compared to other standard therapies for management of OA knee pain. The most common adverse event associated with HAs is mild injection site pain and swelling. Each product has had rare reports of pseudogout and anaphylactoid reactions. Product-specific adverse events, severe acute inflammatory reactions (pseudoseptic knee), in patients receiving Synvisc have been reported. One such patient developed antibodies to chicken proteins and hylan, suggesting an immunologic basis for the severe acute inflammatory reaction. Data from an animal study support a possible immunogenic difference between Synvisc and Hyalgan. Conclusions and Relevance: Overall, HA therapy is a safe treatment for OA knee pain, although there may be interproduct variability in safety profiles. Semin Arthritis Rheum 32:296-309. Copyright 2003, Elsevier Inc. All rights reserved.

Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action.

Although the predominant mechanism of intra-articular hyaluronan (hyaluronic acid) (HA) and hylans for the treatment of pain associated with knee osteoarthritis (OA) is unknown, in vivo, in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. HA can reduce nerve impulses and nerve sensitivity associated with the pain of OA. In experimental OA, this glycosaminoglycan has protective effects on cartilage, which may be mediated by its molecular and cellular effects observed in vitro. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the production and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. Many of the physiological effects of exogenous HA may be a function of its molecular weight. Several physiological effects probably contribute to the mechanisms by which HA and hylans exert their clinical effects in knee OA.

The use of intra-articular Na-hyaluronate as a potential chondroprotective device in experimentally induced acute articular cartilage injury and repair in rabbits

Objective: This study examined if viscosupplementation from intra-articular administration of a commercially available form of hyaluronan (HA) could promote the restoration of proteoglycan (PG) depletion induced by chymopapain and then if the repair could be maintained once HA treatment was discontinued. Methods: Animals received cartilage injury with intra-articular chymopapain (2.0 mg) followed by weekly treatment with intra-articular HA. HA treated animals were compared to injured animals with no treatment, contralateral untreated joints and joints from normal controls. The effect of intra-articular HA alone on articular cartilage was also examined. Results: Serum keratan sulfate levels confirmed degradation of the cartilage PGs in the chymopapain-injected knees. Intra-articular chymopapain resulted in marked loss of PGs. There were no significant differences among the control groups (untreated control, HA/800 treatment only). HA treatment did not affect the loss of PGs caused by chymopapain after 42 days. However, in animals receiving chymopapain injury followed by weekly HA treatment for 42 days and then 42 days of free cage activity without HA, cartilage PG contents were significantly increased. Intra-articular HA alone had no effect on the articular cartilage. Conclusion: The results in the present study suggest a potential protective effect of HA on chymopapain-induced acute articular cartilage injury in rabbits that, in time, permits damaged cartilage to resynthesize matrix PGs after the HA treatment is discontinued.

Intra-articular hyaluronan: A disease modifying therapy?

Hyaluronan (HA) is a macromolecular glycosaminoglycan which is an important constituent of both synovial fluid and the extracellular matrix of cartilage. Research into the functions of HA have suggested a number of different biophysical, biochemical and cell regulatory roles in joint synovial tissues. Intra-articular HA therapy is now widely used in various countries for the treatment of osteoarthritis (OA) in both humans and animals. Numerous high purity pharmaceutical preparations are commercially available which have a variety of forms and molecular weights ranging from less than 1.0 × 106 Da (generally regarded as low molecular weight) up to 3–6.0 × 106 Da (high molecular weight). This range of molecular weights in the commercially available preparations is a direct reflection of the variation in results derived from both in vitro and in vivo studies of the use of HA in various experimental models. Intra-articular HA therapy has been registered by some companies as a device rather than a drug, which reflects both the initial theory that HA exerted its action through viscosupplementation of deficient synovial fluid, and the current scientific debate as to the specific therapeutic effects of HA on synovial tissues. Significant research is ongoing to further define the likely multiple actions of HA on joint tissues. The discovery that HA is rapidly cleared from joints after intra-articular injection, coupled with the realization that the symptomatic relief experienced by human OA patients treated by intra-articular HA, together suggest that viscosupplementation is not the only mode of action of HA. Studies in various animal models of inflammation and pain have supported an anti-inflammatory action of HA in joint disease. In vivo animal studies using models of OA suggest that low molecular weight HA provides better protection of cartilage than high molecular weight preparations. This is in direct contrast to the results of in vitro studies using chondrocyte or cartilage explant cultures in which high molecular weight HA preparations were found to be more effective at protecting cartilage from degradation than low molecular weight preparations. Evidence that low molecular weight forms of HA penetrate the joint tissues more deeply is a partial explanation for this, as it is likely that the low molecular weight HA is able to achieve higher concentrations of the drug in the pericellular environment. However, recent research has provided additional evidence of specific interaction between HA, various cell receptors such as CD44. This, together with other studies in cell biology which have demonstrated that signal transduction and gene expression arise from HA receptor binding suggest an immunoregulatory role for HA. Our present knowledge of interactions of HA at the cellular and molecular level is still inadequate, but there is strong evidence from animal model experiments as well as from studies on human synovial biopsies that the positive effects exhibited by HA in OA joints are largely mediated by its anti-inflammatory, cytoprotective and immunoregulatory properties. There is significant scientific evidence that intra-articular HA therapy can provide cartilage protection. However, this probably does not arise from a direct effect of HA on chondrocytes, but rather is secondary to the down regulation of cytokine, free radical and proteolytic activities in the synovial fluid and synovium, all of which can adversely affect chondrocyte metabolism.

Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: Are the effects molecular weight dependent?

Background: Hyaluronan, or hyaluronic acid (HA), is the major hydrodynamic nonprotein component of joint synovial fluid (SF). Its unique viscoelastic properties confer remarkable shock absorbing and lubricating abilities to SF, while its enormous macromolecular size and hydrophilicity serve to retain fluid in the joint cavity during articulation. HA restricts the entry of large plasma proteins and cells into SF but facilitates solute exchange between the synovial capillaries and cartilage and other joint tissues. In addition, HA can form a pericellular coat around cells, interact with proinflammatory mediators, and bind to cell receptors, such as cluster determinant (CD)44 and receptor for hyaluronate-mediated motility (RHAMM), where it modulates cell proliferation, migration, and gene expression. All these physicochemical and biologic properties of HA have been shown to be molecular weight (MW) dependent. Objective: Intra-articular (IA) HA therapy has been used for the treatment of knee osteoarthritis (OA) for more than 30 years. However, the mechanisms responsible for the reported beneficial clinical effects of this form of treatment remain contentious. Furthermore, there are a variety of pharmaceutic HA preparations of different MW available for the treatment of OA, but the significance of their MWs with respect to their pharmacologic activities have not been reviewed previously. The objective of the present review is to redress this deficiency. Methods: We reviewed in vitro and in vivo reports to identify those pharmacologic activities of HA that were considered relevant to the ability of this agent to relieve symptoms and protect joint tissues in OA. Where possible, reports were selected for inclusion when the pharmacologic effects of HA had been studied in relation to its MW. In many studies, only a single HA preparation had been investigated. In these instances, the experimental outcomes reported were compared with similar studies undertaken with HAs of different MWs. Results: Although in vitro studies have generally indicated that high MW-HA preparations were more biologically active than HAs of lower MW, this finding was not confirmed using animal models of OA. The discrepancy may be partly explained by the enhanced penetration of the lower MW HA preparation through the extracellular matrix of the synovium, thereby maximizing its concentration and facilitating its interaction with target synovial cells. However, there is accumulating experimental evidence to show that the binding of HAs to their cellular receptors is dependent on their molecular size; the smaller HA molecular species often elicits an opposite cellular response to that produced by the higher MW preparations. Studies using large animal models of OA have shown that HAs with MWs within the range of 0.5 × 106-1.0 × 106 Da were generally more effective in reducing indices of synovial inflammation and restoring the rheological properties of SF (visco-induction) than HAs with MW > 2.3 × 106 Da. These experimental findings were consistent with light and electron microscopic studies of synovial membrane and cartilage biopsy specimens obtained from OA patients administered 5 weekly IA injections of HA of MW = 0.5 × 106-0.73 × 106 Da in which evidence of partial restoration of normal joint tissue metabolism was obtained. Conclusions: By mitigating the activities of proinflammatory mediators and pain producing neuropeptides released by activated synovial cells, HA may improve the symptoms of OA. In addition, HAs within the MW range of 0.5 × 106-1.0 × 106 Da partially restore SF rheological properties and synovial fibroblast metabolism in animal models. These pharmacologic activities of HA could account for the reported long-term clinical benefits of this OA therapy. However, clinical evidence has yet to be described to support the animal studies that indicated that HAs with MW > 2.3 × 106 Da may be less effective in restoring SF rheology than HAs of half this size. Semin Arthritis Rheum 32:10-37. Copyright 2002, Elsevier Science (USA). All rights reserved.

Retrospective Study of Outcomes in Hyalgan??-Treated* Patients with Osteoarthritis of the Knee

To evaluate therapeutic success [defined as lack of total knee replacement surgery (TKR) or other significant clinical intervention during a 6-month follow-up] and to identify baseline patient and disease characteristics associated with improved pain relief and quality of life (QOL) in patients in a clinical practice who were treated with a single course of Hyalgan® (intra-articular hyaluronan) for pain associated with osteoarthritis (OA) of the knee. This was an uncontrolled, retrospective study conducted at a single US clinical orthopaedic practice. 248 patients with moderate to severe OA of the knee. All patients received a single course of intra-articular Hyalgan® therapy during an 18-month period, and had a radiogram of the treated knee within the 6 months before treatment. A total of 218 of 363 (60.1%) knees (248 patients) with moderate to severe OA were judged successfully treated over a 6-month follow-up period; only 20.3% of cases required TKR. On the basis of a multivariate analysis that correlated improvements in pain and QOL assessed by a retrospective questionnaire with baseline patient and disease characteristics, taller patients (>165cm), patients with less severe OA, and patients with patellofemoral compartment involvement had the greatest improvement in pain relief and quality of life following treatment with Hyalgan®. Hyalgan® was effective in patients with moderate to severe OA, and may have delayed TKR in 80% of patients. Taller patients, patients with less severe OA, and patients with patellofemoral compartment involvement showed the greatest pain relief and improvements in QOL.

Pharmacological therapies for the treatment of osteoarthritis.

Non-pharmacological interventions are the first-line therapy for osteoarthritis. If non-pharmacological therapy fails, paracetamol (up to 4 g daily) should be added. If paracetamol fails, the patient's risk factors for gastrointestinal and renal disease should be assessed. In patients with gastrointestinal risk factors, a COX-2-specific inhibitor (CSI) would be used in preference to a conventional non-steroidal anti-inflammatory drug (NSAID). In patients with renal risk factors, NSAIDs and CSIs should be used with care. In patients who continue to have problems, other treatments should be considered; these might include intra-articular hyaluronan or depot corticosteroid, analgesia or glucosamine.

PB22 Intra-articular hyaluronate efficacy and safety in treatment of knee OA

PB22 Intra-articular hyaluronate efficacy and safety in treatment of knee OA

Hyaluronan molecular weight and polydispersity in some commercial intra-articular injectable preparations and in synovial fluid.

Hyaluronan is the major non-proteinaceous component of joint synovial fluid and is responsible for the unique rheological and biological properties of this medium. In joint arthropathies the molecular weight and concentration of hyaluronan may change, thereby influencing joint physiology and function. Intra-articular administrated hyaluronan derived from a number of sources, has been used for the treatment of osteoarthritis, however, there is limited information on the molecular weight and polydispersity of these various commercial preparations. The objective of this study was to develop an accurate, convenient method by which the molecular weight and polydispersity of hyaluronan may be determined and then applied to characterise the hyaluronan in synovial fluid. Characterisation of the molecular parameters of hyaluronan of different origins and in ovine synovial fluid was accomplished using a multi-angle laser-light scattering (MALLS) detector coupled to a gel permeation chromatography (GPC) system, fitted with an automatic sample injector. Seven commercially available hyaluronan preparations of reported molecular weight were analysed. The weight average molecular weight (Mw) and number average molecular weight (Mn) values obtained for 6 of the 7 preparations using the MALLS-GPC system were in good agreement with the reported values. The abnormally low values for the exception suggested that degradation of hyaluronan had occurred. The MALLS-GPC technique was then used to determine the molecular characteristics of the endogenous hyaluronan in normal ovine synovial fluids. While the Mws ranged from less than 1 x 10(6) Da to 7 x 10(6) Da the majority were between 1-3 x 10(6) Da. [mean Mw = 2.42 x 10(6), mean Mn = 2.21 x 10(6) Da]. The effects of freezing and thawing synovial fluid upon molecular weight of hyaluronan were also investigated and were found to diminish both Mz and Mw values.