Intra-articular Injection Of Sodium Hyaluronate Research Articles

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.

P188 A study of the safety and efficacy of intra-articular high molecular weight natural sodium hyaluronate injections in single and two injection regimens in patients with idiopathic osteoarthritis of the knee

P188 A study of the safety and efficacy of intra-articular high molecular weight natural sodium hyaluronate injections in single and two injection regimens in patients with idiopathic osteoarthritis of the knee

Poster 195 evaluation of fluoroscopic and arthrographically guided intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee: A preliminary report. Ramon Castellanos, MD (Int Pain Inst, Coral Gables, FL); Tania Castellanos, RN, CNOR, e-mail: morro94@bellsouth.net

Poster 195 evaluation of fluoroscopic and arthrographically guided intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee: A preliminary report. Ramon Castellanos, MD (Int Pain Inst, Coral Gables, FL); Tania Castellanos, RN, CNOR, e-mail: morro94@bellsouth.net

The effects of intraarticularly injected sodium hyaluronate on levels of intact aggrecan and nitric oxide in the joint fluid of patients with knee osteoarthritis

Objective Intraarticular injections of sodium hyaluronate (Na-HA) appear effective in reducing subjective symptoms of osteoarthritis (OA) and may also have protective effects on the cartilage matrix. The present study analyzed the suppressive effects of Na-HA on the release and degradation of aggrecan and on levels of nitric oxide (NO) in the joint fluid of patients with knee OA. Design Sixteen OA patients with knee joint effusion were treated by 5 weekly intraarticular injections of Na-HA. Prior to each Na-HA injection, joint fluid was collected to determine the levels of chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate (C6S), intact aggrecan and NO. Results One week after the final injection, the joint fluid levels of C4S, C6S, and NO were significantly decreased. In contrast, the joint fluid level of intact aggrecan was stable during the series of Na-HA injections. A trend was seen for a positive correlation ( P<0.1) between the clinical score and C4S or C6S joint fluid levels, and for a negative correlation between the joint fluid levels of intact aggrecan and C4S or C6S. No significant correlations were observed between joint fluid levels of NO, the clinical score, and levels of C4S, C6S, and intact aggrecan. Conclusion The results of this study suggest that intraarticularly injected Na-HA is able to improve the clinical symptoms of OA partially based on its ability to reduce the release and degradation of aggrecan and/or to enhance the synthesis of aggrecan in the joint tissues of the patients with knee OA. While Na-HA also reduces the NO level in the joint fluid of patients with knee OA, this effect may be independent from the other effects of Na-HA.

Efficacy of Intra-articular Sodium Hyaluronate in Patients with Osteoarthritis of the Knee

Background: Osteoarthritis of the knee joint is a chronic disease associated with degenerative change in the constituents of the knee joint, which is characterized by the slow degradation of cartilage, pain and increasing disability. Traditional treatments for osteoarthritis include weight loss, muscle strengthening exercise, simple analgesics, non-steroidal anti-inflammatory drugs, intra-articular corticosteroids and surgery, but drug treatments have various adverse reactions. Although some assessments of sodium hyaluronate have indicated clinical improvement in the majority of cases, the therapeutic effects of an intra-articular injection of sodium hyaluronate on osteoarthritis of the knee is still in question. Therefore, the present study was undertaken to elucidate the therapeutic efficacy and safety of an intra-articular injection of sodium hyaluronate for osteoarthritis of the knee. Methods: A randomized clinical trial was carried out in 35 patients with osteoarthritis of the knee to evaluate the efficacy and tolerability of an intra-articular injection of 25 mg sodium hyaluronate once a week, for 5 consecutive weeks. The final evaluation was assessed by pain at rest, pain on walking, tenderness of the joint line before the study initiation, and at the 2nd, 4th and 6th weeks after the end of the injections. The level of knee pain was evaluated using a 100 mm VAS (visual analog scale). Results: The pain at rest, as assessed by the visual analog scale (VAS), showed a statistically significant (P

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 treatment of osteoarthritis of the knee: an arthroscopic and clinical comparison between sodium hyaluronate (500-730 kDa) and methylprednisolone acetate

Corticosteroids have long represented the drugs of choice for intra-articular treatment of osteoarthritis (OA), but their use has drawbacks, indicating the need for alternatives devoid of these effects. This comparative study examined the clinical efficacy and the structural effects of intra-articular injections of sodium hyaluronate (HA) of molecular weight (MW) 500–730 kDa (one injection weekly for 5 weeks) versus methylprednisolone acetate (MP) (one injection weekly for 3 weeks) in the treatment knee OA. We studied 99 patients with knee OA, primary or secondary to a traumatic event, classified according to criteria of the American College of Rheumatology. Pain assessments by VAS and arthroscopic examinations of synovial membrane and cartilage were performed at baseline and 180 days after the start of the treatment. Arthroscopic features were evaluated under blind conditions. Initially, MP showed a more immediate beneficial clinical effect in reducing pain than HA, but after 180 days the symptomatic effect of HA was more long lasting than that of MP. Arthroscopic findings at day 180, in comparison with baseline conditions, showed that both drugs were decreased synovial membrane inflammation but HA was superior to MP in reducing the grade and extent of cartilage damage. HA of 500–730 kDa represents a valid alternative to corticosteroids in the intra-articular treatment of OA with a beneficial effect on the structural alterations. This study supports previous data on a potential structure-modifying activity of HA in OA of the knee.

Arthrocentesis with sodium hyaluronate is more effective than arthrocentesis alone in temporomandibular joint treatment

Question: Is arthrocentesis with sodium hyaluronate more effective than arthrocentesis alone in people with temporomandibular joint derangements? Objective To investigate the efficacy of arthrocentesis with and without injection of sodium hyaluronate (SH) into the upper joint space in the treatment of temporomandibular joint (TMJ) internal derangements. Design Randomised non-blinded prospective trial. Intervention Thirty-one people (five males and 26 females, age 14–53 years) who had TMJ problems in 41 joints were randomly divided into two treatment groups. One group received arthrocentesis alone, the other arthrocentesis plus intra-articular injection of SH. Both groups contained patients with disc displacement with reduction and with closed lock. Patients were evaluated before the procedure, on postoperative day 1 and then regularly for 24 months. Outcome measures Intensity of TMJ pain, jaw function and clicking sounds in the TMJ were assessed using visual analogue scales (VAS). Maximal mouth opening and lateral jaw movements also were recorded at each follow-up visit. Results Both techniques increased maximal mouth opening, lateral movements and function while reducing TMJ pain and noise. Maximal jaw opening increased at 24 months in both groups (see Table 1). Conclusions Patients benefited from both techniques but arthrocentesis with injection of SH seemed to be superior to arthrocentesis alone. Jaw function improved and maximal mouth opening increased earlier and continued longer in arthrocentesis and SH group.

Treatment of patients with arthrosis of the temporomandibular joint by infiltration of sodium hyaluronate: a preliminary study.

Patients with degenerative disease of the temporomandibular joint (TMJ) who did not respond to conservative medical therapy (splint therapy, selected grinding or physiotherapy) can be treated by arthrocentesis, which is associated with intra-articular injections of sodium hyaluronate (Hyalgan). In this study, we treated ten dysfunctional patients with degenerative joint disease (DJD) who had been diagnosed clinically and had had the diagnosis confirmed by MRI. All subjects presented impaired mouth opening, joint pain at rest and on movement and impaired masticatory efficiency. We performed one cycle of five infiltrations with joint arthrocentesis and the injection of sodium hyaluronate at weekly intervals. The following parameters were assessed before and after infiltration and at follow-up after 6 months: mouth opening (with a mean of between 36.5 mm and 41.9 mm); sideways movements (to the right 4.9 mm to 8.9 mm and to the left 4.7 mm to 9.2 mm); pain at rest (VAS=1.8 to 0.5) and on movement (VAS=7.8 to 1.1); masticatory efficiency (VAS=5.7 to 8.6); subjective judgement of the functional TMJ limitation level (from 2.8 to 0.8); judgement of efficacy (from 2.4 to 3.2); judgement of tolerability to the therapy (from 2.0 to 3.1). The therapeutic benefits observed can be attributed both to joint arthrocentesis and to the characteristics of sodium hyaluronate itself. All the parameters considered revealed a statistically significant positive variation that persisted over time ( P<0.05). The results obtained by this minimally invasive, fast and easy technique proved to be valid and lasting. This infiltration technique using sodium hyaluronate looks very promising for patients affected by symptomatic DJD who do not respond to conservative medical therapy, reflecting similarly encouraging findings in the orthopaedic treatment of degenerative knee pathology.

Laser-Facilitated arthrodesis of the distal tarsal joints

Abstract Arthritis of the distal tarsal joints is a common cause of lameness in performance horses. Clinical signs of distal tarsal arthritis are variable and may include gait abnormalities typical for tarsal lameness, including accentuated elevation of the affected limb, shortened cranial phase of the stride, and decreased arc of the foot. Affected horses frequently resent palpation of the lumbar and gluteal musculature. The lameness is usually increased after a hind limb flexion test. This condition is most commonly treated with intra-articular injections of sodium hyaluronate and corticosteroids in conjunction with controlled exercise and systemic nonsteroidal anti-inflammatory medication. Horses that are refractory to this form of treatment have traditionally been treated by cunean tenectomy with inconsistent results. Various surgical techniques have been used to achieve arthrodesis of these joints in an effort to eliminate the lameness associated with arthritic changes in these joints. Laser-assisted arthrodesis offers a minimally invasive surgical procedure with a relatively short convalescent period that eliminates the clinical signs of lameness in a high number of cases.

Cartilage and bone biological markers in the synovial fluid of osteoarthritic patients after hyaluronan injections in the knee

Objective: To evaluate synovial fluid levels of cartilage and bone biological markers after repetitive intra-articular injections of sodium hyaluronate (HA) in knee osteoarthritis (OA) patients. Methods: Twenty patients with knee OA were evaluated before and after 5 weekly injections of HA. To study cartilage and bone biological markers, synovial fluid and urine samples were collected simultaneously with the first (FI=week 0) and before the last injection (LI=week 4) of HA. Not commercially available markers (cartilage oligomeric matrix protein (COMP), proteoglycan monomers and cyanogen bromide peptide 11 of the type II collagen chains (α (II) CA11B)) were determined by an indirect inhibition ELISA developed and standardized in our laboratory. Results: We found a significant reduction in levels of proteoglycan monomers (30±16 vs. 22±10 μg/ml, p<0.05), an increase in COMP concentration (2.9±0.9 vs. 3.6±0.9 μg/ml, p<0.05) and osteocalcin (BGP) levels (8.7±8 vs. 11.9±9 ng/ml, p<0.05). No significant changes were observed in the levels of α (II)CB11B), metalloproteinase-1 (MMP-1) or pyridinium cross-link/creatinine (Pyr/Cr). Conclusions: HA could elicit an indirect response on the cartilage and bone metabolism due to the increased overuse of the joint caused by the analgesic effect of HA. However, a direct HA action on the metabolism of chondrocytes must not be ruled out.

Efficacy of temporomandibular joint arthrocentesis with and without injection of sodium hyaluronate in treatment of internal derangements

Purpose: This study was designed to investigate the efficacy of arthrocentesis with and without injection of sodium hyaluronate (SH) into the upper joint space in the treatment of temporomandibular joint (TMJ) internal derangements. Patients and Methods: Forty-one TMJs in 5 males and 26 females aged 14 to 53 years comprised the study material. The patients' complaints were limited mouth opening, TMJ pain and tenderness, and joint noises during function. Patients were randomly divided into 2 groups in which only arthrocentesis was performed in 1 group and arthrocentesis plus intra-articular injection of sodium hyaluronate was performed in the other group. Both groups contained patients with disc displacement with reduction and with closed lock. Clinical evaluation of the patients was done before the procedure, immediately after the procedure, on postoperative day 1, and at 1, 2, 3, 4, 5, 6, 9, 12, 18, and 24 months postoperatively. Intensity of TMJ pain, jaw function, and clicking sounds in the TMJ were assessed using visual analog scales. Maximal mouth opening and lateral jaw movements also were recorded at each follow-up visit. Results: Both techniques increased maximal mouth opening, lateral movements, and function, while reducing TMJ pain and noise. Conclusions: Although patients benefitted from both techniques, arthrocentesis with injection of SH seemed to be superior to arthrocentesis alone. © 2001 American Association of Oral and Maxillofacial Surgeons

Effect of arthrocentesis and sodium hyaluronate injection on nitrite, nitrate, and thiobarbituric acid-reactive substance levels in the synovial fluid

To evaluate the effect of arthrocentesis and sodium hyaluronate (SH) injections on nitrite, nitrate, and thiobarbituric acid-reactive substance (TBA-RS) levels in temporomandibular joint internal derangements. Arthrocentesis was performed on 10 patients, and 15 patients received a supplemental injection of SH after arthrocentesis. All these patients received an SH injection 15 days after the first intervention. The synovial fluid samples were obtained before arthrocentesis on the first appointment and before the SH injection 15 days later. Nitrite and nitrate levels were measured with a highly sensitive and specific chemiluminescence detection method, and the concentration of lipid peroxidation products was assessed by means of the thiobarbituric acid reaction. Symptomatic improvement was seen in both groups. Nitrite, nitrate, and TBA-RS levels only decreased significantly (P <.05) with a supplemental SH injection after arthrocentesis. Intra-articular injections of SH may reduce nitrite, nitrate, and TBA-RS levels that play a role in the pathogenesis of various temporomandibular disorders.

Influence of intra‐articular sodium hyaluronate and polysulphated glycosaminoglycans on the biochemical composition of equine articular surface repair tissue

The influence of repeated intra-articular injections of sodium hyaluronate and polysulphated glycosaminoglycan on the repair of full-thickness osteochondral defects was examined in the midcarpal joints of ponies. The study showed no significant difference between treated and control groups with regard to total collagen content, uronic acid content or the relative proportions of Type I and Type II collagen in the repair tissue, indicating that the drugs did not affect the biochemical composition of the repair tissue 11 weeks after defect induction.

Intra-Articular Injection of Sodium Hyaluronate in Patients with Rheumatoid Arthritis

Intra-Articular Injection of Sodium Hyaluronate in Patients with Rheumatoid Arthritis

Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study

The efficacy and the safety of intra-articular injections of sodium hyaluronate were studied in patients with osteoarthritis of the knee in a randomized multicenter double-blind study. Two hundred and nine patients received five injections of either 25 mg hyaluronate/2.5 ml (verum, N = 102) or 0.25 mg hyaluronate/2.5 ml (control, N = 107) at weekly intervals. Seven patients in each group were excluded from the protocol-correct efficacy analysis. The Lequesne Index, the first main criterion, showed a significant superiority of the verum-treated patients after the third injection up to the final follow-up examination 9 weeks after the last injection (MANOVA, P < 0.025). The consumption of paracetamol was defined as a complementary main criterion that did not reveal significant differences between the treatment groups. Most of the individual secondary endpoints demonstrated a much better response to the active treatment without reaching the significance level in the intergroup comparisons for the single time-points. Side-effects were confined to local reactions of minor severity and short duration in four patients (six events) of the verum group and in five patients of the control group. Clinical chemistry and hematology remained essentially unchanged.

変形性膝関節症に対する高分子量ヒアルロン酸ナトリウム（ＳＰＨ）の使用経験 特に関節鏡所見について

The result of intraarticular injection of high molecular weight sodium hyaluronate in the knee joint were reviewed. Twelve knees in 12 patients were divided into two groups: Group A consisted of 10 patients with osteoarthritis in the medial compartment of the knee and arthroscopic medial partial meniscectomy had been performed. Group B consisted of 2 patients who had osteoarthritis in the medial compartment of the knee and lateral partial meniscectomy had been performed. After meniscectomy all patients received intraarticular injection of high molecular weight sodium hyaluronate into the knee joint for at least 5 months. After this therapy all knees were arthroscoped again. Improvement was obserbed in both groups.These results suggest that high molecular weight sodium hyaluronate is effective for improvement of degenerative joint cartilage.

顎関節症に対するヒアルロン酸ナトリウムの顎関節腔内注入療法の効果について 特にアラキドン酸代謝産物の消長からみて

We investigated arachidonic acid (AA) metabolites in synovial fluid of 18 patients with temporomandibular joint (TMJ) arthrosis. AA metabolites were separated and quantified by high performance liquid chromatography (HPLC).Among 18 patients, 15 were treated by injections of sodium hyaluronate (SH) into the superior joint compartment of the TMJ. We assessed the effect of treatment clinical symptoms and the generation of AA metabolites.In addition, we measured the leukotrienes (LTs) produced by polymorphonuclear leukocytes (PMNs) obtained from peripheral blood and studied the effect of SH.The following results were obtained:1. Clinical symptoms of TMJ arthrosis improved after intra-articular injections of SH.2. As clinical symptoms improved, AA metabolites decreased.3. SH tended to inhibit the generation of LTs produced by stimulated PMNs.4. This study suggests that TMJ arthrosis is associated with inflammation.

Septic Arthritis of the Distal Interphalangeal Joint in 12 Horses

The medical records of 12 horses with septic arthritis of a distal interphalangeal joint were reviewed to determine clinical features and response to treatment. Sepsis was caused by trauma or an injection that resulted in an open or contaminated distal interphalangeal joint. All horses were severely lame. Treatment included broad-spectrum parenterally administered antimicrobial drugs (ten horses), percutaneous through-and-through joint lavage (eight horses), indwelling drains (three horses), immobilization of the limb in a cast (three horses), intraarticular injection of sodium hyaluronate (one horse), intraarticular injection of antimicrobial drugs (five horses), curettage of the distal phalanx (one horse), and cancellous bone grafting to promote fusion (one horse). Five horses were euthanatized. Ankylosis of the affected joint developed in five horses, four of which are pasture sound. Two horses treated medically are sound although one underwent subsequent palmar digital neurectomy for treatment of navicular syndrome.

Intraarticular Sodium Hyaluronate Injections in the Pond-Nuki Experimental Model of Osteoarthritis in Dogs

The effect of the intraarticular sodium hyaluronate (HA) injection on the osteoarthritic knee joint has been evaluated in dogs using an experimental model of osteoarthritis induced by sectioning the anterior cruciate ligament. Seven weeks after surgery, the damage, graded according to Mankin's scale, was significantly reduced in knee joints treated with HA from the second week postsurgery compared to untreated joints. When intraarticular HA therapy was initiated after the seventh week, osteoarthritis progression was still reduced compared to controls. Both morphology and morphometry showed a beneficial effect of HA on the cartilage response to the damage, as well as a clearcut inhibitory effect on the development of the fibroblastlike cell layer on the articular cartilage in untreated joints. The beneficial effects on the cartilage integrity and response to osteoarthritic damage might be related to a primary effect of HA on the cartilage surface. However, these effects do not exclude the possibility that, in addition, HA might act on the synovial membrane by limiting the synovial reaction.