Intra-articular Hyaluronic Injection Research Articles

A comparison of intra-articular hyaluronan injection accuracy rates between three approaches based on radiographic severity of knee osteoarthritis

To compare the accuracy rates of intra-articular hyaluronic acid (HA) injections for osteoarthritis (OA) of the knee between the modified Waddell approach (an anteromedial approach with manipulative ankle traction at 30 degrees of knee flexion), an anteromedial approach with the subjects seated (hereinafter the seated anteromedial approach) and a lateral patellar approach based on the Kellgren-Lawrence (K-L) radiographic grade (II, III and IV). Fifty patients with knee OA received HA injections through the three approaches. The accuracy rates were confirmed with a single radiograph after injections of a mixture of radiographic contrast medium. In the K-L grade IV cases (n=11), the accuracy rates through the modified Waddell approach (11 out of 11, 100%) were significantly higher than those through the seated anteromedial approach (six out of 11, 55%) and the lateral patellar approach (six out of 11, 55%) (P=0.035). No significant differences were detected in the accuracy rates of the participants classified as grade II (n=21) or III (n=18) cases between the modified Waddell approach (86% and 78%, respectively), the seated anteromedial approach (71% and 56%, respectively) and the lateral patellar approach (86% and 61%, respectively) (P>0.05). Although previous studies have been conducted on the accuracy of needle placement into the intra-articular space of the knee, no evaluations were performed with the results categorized by radiographic severity. This study highlighted the need for clinicians to change the approach employed for HA injections, according to the severity of knee OA.

One intra‐articular injection of hyaluronan prevents cell death and improves cell metabolism in a model of injured articular cartilage in the rabbit

The purpose of this study was to determine the effect of one intra-articular injection of hyaluronan on chondrocyte death and metabolism in injured cartilage. Twenty-three 6-month-old rabbits received partial-thickness articular cartilage defects created on each medial femoral condyle. In order to examine the effect on articular cartilage surrounding iatrogenic cartilage lesions, which can occur during arthroscopic procedures, Study 1 was performed: in 14 rabbits both knees were immediately rinsed with 0.9% NaCl. Experimental knees were treated with hyaluronan. Six rabbits were sacrificed at 2 days; eight rabbits 3 months postoperatively. Histomorphometric analysis was used for studying cell death in cartilage next to the defect. In order to examine the effect on longer lasting lesions, more reflecting the clinical situation, Study 2 was performed: after 6 months knee joints of nine rabbits were (i) irrigated with 0.9% NaCl, (ii) treated with hyaluronan after irrigation with 0.9% NaCl, or (iii) sham-treated. After 7 days patellas were used to study the chondrocyte metabolism by measuring the [(35)S]sulfate incorporation. Study 1: Two days postoperatively, in hyaluronan-treated cartilage the percentage of dead cells was 6.7%, which was significantly lower compared to 16.2% in saline-treated cartilage. After 3 months the percentages of dead cells in both groups were statistically similar. Study 2: Hyaluronan treatment resulted in significantly higher [(35)S]sulfate incorporation compared to knees irrigated with 0.9% NaCl. These results suggest a potential role for hyaluronan in preventing cell death following articular cartilage injury. One injection of hyaluronan improved cartilage metabolism in knees with 6-month-old cartilage defects.

Fibrous change of the infrapatellar fat pad due to strenuous running exercise and its treatment with intraarticular hyaluronan injection in a rat model.

The objective of the study was to determine whether strenuous running exercise produces a significant amount of fibrosis in the infrapatellar fat pad (IFP) of the knee and whether intraarticular injections of hyaluronan (HA) protect fibrosis in the IFP in a rat running model. Strenuous running exercise was performed on a rodent treadmill with 5% inclination using Wistar rats. After the exercise, hyaluronan was injected into the right knee joint once per week in the HA injection group. In the treatment control group of the left knee, no injection was done. Also, the running exercise group and the sedentary control group received no HA injection. The IFP was analyzed histologically and immunohistochemically after 1 week (5 km), 2 weeks (10 km), 3 weeks (15 km) and 6 weeks (30 km). The inflammatory reaction in the IFP was not prominent at each running stage. A slightly, but significantly increased amount of inflammatory cell infiltration appeared during strenuous running. The amount of collagen fibers increased significantly at 30 km stage. Histological scores showed less fibrosis of the IFP in the HA injection group than in the control group at 30 km run. Strenuous running exercise may cause fibrosis in the IFP of runners. Intraarticular HA injection will inhibit arthrofibrosis of painful runners.

Intra-articular Injection of Hyaluronan Diminishes Loss of Chondrocytes in a Rat Immobilized-Knee Model

Joint immobilization is a useful and common treatment modality in orthopedics. However, it also causes unfavorable outcome such as articular cartilage degeneration. Intra-articular injection of hyaluronan has been accepted as a treatment of osteoarthritis, but its effects on immobilized joint remain to be clarified. Hyaluronan is a polysaccharide, distributed ubiquitously in various tissues. In this study, we examined the effect of hyaluronan on the articular cartilage in immobilized joints. The unilateral knee joints of adult male rats were immobilized at 150 degrees in flexion with an internal plate and screws for 1, 2, 4, 6, 8, 12, or 16 weeks (n = 84). Hyaluronan or saline (50 microl/each injection) was administered intra-articularly on the day of surgery and once a week. The articular cartilage from the medial midcondylar region of the knee was obtained, and divided into non-contact, contact and transitional areas (between the non-contact and the contact areas). In each area, a degree of degeneration was evaluated by histomorphometric grading, and measurements of thickness and number of chondrocytes. Histological grading scores in the hyaluronan group were smaller at 12 and 16 weeks compared with those in the saline group. The thickness of the articular cartilage increased in the transitional area in both groups. The number of chondrocytes in the contact and transitional areas gradually decreased, but their number in the hyaluronan group was greater at 12 and 16 weeks compared with that in the saline group. Hyaluronan showed chondroprotective effects on the articular cartilage in a rat immobilized-knee model.

Serum keratan sulfate transiently increases in the early stage of osteoarthritis during strenuous running of rats: protective effect of intraarticular hyaluronan injection

IntroductionOsteoarthritis is influenced by genetic and environment factors, including mechanical stress; however, the relationship between running and the development of osteoarthritis remains a matter of controversy. We investigated whether osteoarthritic change could be obtained in a rat strenuous running model, whether serum keratan sulfate in rats could be detected by HPLC and was associated with onset or progression of osteoarthritis, and whether hyaluronan injection suppressed development of osteoarthritis and elevation of serum keratan sulfate.MethodsWistar rats were forced to run 30 km in 6 weeks on a treadmill machine. Articular cartilage of the knees was evaluated macroscopically and immunohistologically. Serum keratan sulfate was examined every week by HPLC. The effect of weekly knee injection of hyaluronan was also investigated.ResultsCartilage surfaces stained with India ink became irregular, metachromasia by safranin-O staining appeared to be almost lost, and Mankin's score significantly worsened after 30 km of running. Serum keratan sulfate in rats was detected by HPLC and transiently increased (peaked at 3 to 4 weeks) along with depletion of keratan sulfate in cartilage tissue. Hyaluronan treatment suppressed morphological progression of osteoarthritis and elevation of serum keratan sulfate.ConclusionRat strenuous running induced osteoarthritis. Serum keratan sulfate was associated with progression of osteoarthritis. Weekly intraarticular injection of hyaluronan controlled the development of osteoarthritis, and the effect was reflected by serum keratan sulfate.

Hyaluronan Suppresses IL-1β-induced Metalloproteinase Activity from Synovial Tissue

Intraarticular injection of hyaluronan (viscosupplementation) is commonly used to treat knee pain from osteoarthritis. The therapeutic benefit might derive from hyaluronan inhibition of the activity of the cytokine-regulated catabolic enzymes that attack joint cartilage (matrix metalloproteinases). We tested the hypothesis that hyaluronan inhibited interleukin-1beta-induced matrix metalloproteinase activity secreted by explants of synovial tissue from patients with osteoarthritis and investigated the mechanism of the effect. Hyaluronan with a molecular mass of 12.8 MDa (number average) antagonized induced metalloproteinase activity in proportion to hyaluronan concentration in the clinically relevant range of 2 to 8 mg/mL. The effect was not attributable solely to molecular mass because 1.2-MDa hyaluronan produced comparable inhibition. Based on measurements involving hyaluronans of different average molecular masses, polydispersity and viscosity were similarly ruled out as primary responsible factors. The effect of hyaluronan on induced metalloproteinase activity was mediated partially by CD44, the principal cell surface receptor for hyaluronan. Hyaluronan inhibited interleukin-1beta-induced metalloproteinase production from osteoarthritic synovial tissue by a process that was not solely dependent on hyaluronan molecular mass but that was partly mediated by hyaluronan binding to CD44. The efficacy of viscosupplementation could be explained if hyaluronan also blocked catabolic enzyme activity in the joint.

Attack of Gouty Arthritis after Intraarticular Injection of Naturally Derived Hyaluronic Acid

Viscosupplementation by intraarticular administration of exogenous hyaluronic acid has been a favorable treatment option to alleviate the symptoms of knee osteoarthritis. The potential but uncommon adverse reactions associated with intraarticular hyaluronic acid injection are local pain, swelling, and allergic response. These reactions are typically mild, transient, and self-limiting. The focus of this report is an 80-year-old man who presented with acute painful swelling of his knee joint after an injection of naturally derived hyaluronic acid. Aspiration of knee joint effusion yielded 40 mL of turbid straw-colored fluid. Synovial fluid cell counts revealed numerous leukocytes with a marked predominance of neutrophils. Intraleukocytic needle-shaped crystals with intensely negative birefringence were identified with polarized light microscopy, indicating monosodium urate crystals that are typically seen in acute gouty arthritis. The synovial fluid was sterile in culture. His knee pain reduced significantly after arthrocentesis and non-steroidal anti-inflammatory drug treatment. To the best of our knowledge, this is the first description of an attack of acute gout following intraarticular injection of naturally derived hyaluronic acid. The possible mechanisms were discussed with a review of the relevant literature.

Changes in biochemical markers and prediction of effectiveness of intra-articular hyaluronan in patients with knee osteoarthritis

Intra-articular injection of hyaluronan (HA) is frequently used to treat knee osteoarthritis (OA). We studied whether HA injections induced significant changes in levels of biochemical markers in synovial fluid (SF). In addition, we investigated the possibility of predicting the effectiveness of HA based on these biochemical markers. Twenty-eight patients with knee OA underwent five weekly intra-articular injections of HA. Knee pain was measured on visual analog scale (VAS) before and after the five injections. Levels of biochemical markers, including chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), keratan sulfate (KS), and tenascin-C (TN-C), were determined before and after the five injections. Correlations between the biochemical markers before HA injection and the improvement of VAS after the five injections were evaluated. After HA injections, levels of C6S, C4S, and KS decreased significantly. Inverse correlations were observed between the levels of TN-C and C4S before HA injection and improvement of VAS after the five injections. In contrast, no significant correlation was seen between levels of C6S and KS before injections and improvement of VAS after the five injections. The reduction in C6S, C4S, and KS levels after HA injections reflects that HA could help maintain normal cartilage metabolism. Our findings suggest that HA injections are effective in patients whose knees contain low levels of TN-C and C4S, reflecting an early stage of OA and limited synovitis.

Intra-articular injection of hyaluronate and indomethacin in rabbits with antigen-induced arthritis

Combined effects of hyaluronate and indomethacin in the treatment of rabbits with antigen-induced arthritis (AIA) were evaluated by assessing joint swelling, C-reactive protein (CRP) and prostaglandin E(2) (PGE(2)) levels with periodic intra-articular (ia) injections of hyaluronate alone (HA group) and with either a low or high concentration of indomethacin (LI-HA or HI-HA group). End-point analyses included matrix metalloproteinases-3 (MMP-3) activity and macroscopic and histological joint examinations. Results demonstrated that treatment in LI-HA and HI-HA groups resulted in statistically significant suppression of CRP, PGE(2, )and MMP-3 in comparison with those of HA group. Inhibition of serum CRP was only observed in LI-HA group. The order of serum MMP-3 inhibition was LI-HA>HI-HA>HA. Based on macroscopic and histological analyses of pannus formation, hyperplasia, inflammation, joint leakage and erosion, and loss of proteoglycan, the only statistically significant improvement was shown in LI-HA group compared to HA group and HI-HA group compared to control group.

Acute pseudoseptic arthritis after viscosupplementation of the knee: a case report

Intra-articular injections of hyaluronan are generally well tolerated; the most common adverse event associated with their use is an inflammatory reaction or a flare at the injection site. Naturally derived sodium hyaluronates have not been associated with pseudosepsis; we describe a case of severe arthritis mimicking acute septic arthritis after naturally hyaluronan. A 70-year-old woman had a medial femorotibial and patellofemoral compartment knee osteoarthritis. Hyaluronic acid injection was indicated because of the persistence of a pain while walking and restricted ability to walk 100 m, as well as the installation of a flessum. She was admitted for an evaluation of a joint effusion occurring within 48 h after the first hyaluronic acid intra-articular injection (first course), with no fever or chills. Joint fluid was found to be cloudy and contained 24,000 cells per mm(3). A knee aspiration was performed to evaluate the possibility of a joint infection. The examination of synovial fluid under phase contrast and polarizing microscopes showed no crystals, and culture on standard media was negative. Acute septic arthritis was considered to be the most likely diagnosis, and probabilistic antibiotic therapy was started. The result of the bacteriological examinations also returned negative. The absence of general signs, particularly fever and chills, with fast effusion regression in less than 4 days did not plead in favor of a septic origin. In front of this beam of arguments, antibiotic therapy was stopped after 4 days. The nonsteroidal anti-inflammatory drug (Nimésulide) was given. The clinical and laboratory test abnormalities were normalized within 2 weeks. Our case has the particularity to occur after using Curavisc, which is known as producing no allergenic reactions. Moreover, the described reaction occurred with the very first infiltration within the very first course.

Reduced Pain of Intraarticular Hyaluronate Injection With the Reciprocating Procedure Device

Greater than 50% of patients report significant pain with intraarticular injection of hyaluronate. The reciprocating procedure device (RPD), also known the reciprocating syringe, has 2 plungers that reciprocate with each other, permitting one-handed operation. The RPD increases physician control of the needle and is proposed to reduce patient pain during syringe procedures. To determine in a randomized controlled trial whether the RPD induces less pain than the traditional syringe during intraarticular hyaluronate therapy for the knee. Eighty intraarticular injection procedures of the knee were randomized to either the conventional syringe or the RPD using hyaluronate sodium derivative (Hylan G-F-20). Outcome measures included physician's estimate of pain, patient pain (Visual Analogue Pain Scale [VAPS]), procedure duration, operator satisfaction, complications, and response to the injected medication. Patients reported 85% more pain than physicians estimated. Fifty-one percent (19/37) of subjects experienced moderate to severe pain with the conventional syringe, while only 14% (6/43) experienced pain with the RPD. The RPD reduced pain scores (RPD VAPS score: 2.12 +/- 2.15; conventional syringe VAPS score: 4.22 +/- 3.25; P < 0.001), reduced procedure time (RPD: 1.34 +/- 1.09, conventional syringe: 1.90 +/- 1.35 minutes, P < 0.001), and improved physician satisfaction (RPD VASS Score: 9.02 +/- 0.80, conventional syringe 5.69 +/- 1.33, P < 0.001). Patients have considerably more pain with intraarticular needle introduction and injectable hyaluronate therapy than physicians estimate. The RPD reduces patient pain, reduces procedure time, and improves needle introduction compared with the conventional syringe for hyaluronate injection therapy for the knee.

Efficacy and Safety of Hyaluronan Treatment in Combination Therapy With Home Exercise for Knee Osteoarthritis Pain

Stitik TP, Blacksin MF, Stiskal DM, Kim JH, Foye PM, Schoenherr L, Choi E-S, Chen B, Saunders HJ, Nadler SF. Efficacy and safety of hyaluronan treatment in combination therapy with home exercise for knee osteoarthritis pain. Objective To assess the efficacy and safety of intra-articular injections of sodium hyaluronate combined with a home exercise program (HEP) in the management of pain associated with osteoarthritis (OA) of the knee. Design Single-blinded, parallel-design, 1-year clinical study with sequential enrollment. Setting University-based outpatient physiatric practice. Participants Sixty patients (18 men, 42 women; age, ≥50y) with moderate-to-severe pain associated with OA of the knee. Interventions (1) Five weekly intra-articular hyaluronate injections (5-HYL); (2) 3 weekly intra-articular hyaluronate injections (3-HYL); or (3) a combination of an HEP with 3 weekly intra-articular hyaluronate injections (3-HYL+HEP). Main Outcome Measures The primary outcome measure was a 100-mm visual analog scale for pain after a 50-foot walk (15.24m). Secondary measures included the Western Ontario and McMaster Universities Osteoarthritis Index subscales. Results The 3-HYL+HEP group had significantly faster onset of pain relief compared with the 3-HYL ( P<.01) and 5-HYL groups ( P=.01). All groups showed a mean symptomatic improvement from baseline (reduction in baseline pain at 3mo was 59%, 49%, and 48% for the 3-HYL+HEP, 3-HYL, and 5-HYL groups, respectively) that was clinically and statistically significant. There were no between-group differences in the incidence or nature of adverse events. Conclusions The combined use of hyaluronate injections with HEP should be considered for management of moderate-to-severe pain in patients with knee OA.

RANDOMIZED CONTROLLED TRIAL OF THE RECIPROCATING PROCEDURE DEVICE IN DEEP SYRINGE PROCEDURES.

Purpose The reciprocating procedure device (RPD) has been demonstrated to be clinically superior to the conventional syringe in deep needle and syringe procedures, including arthrocentesis, aspiration biopsy, and intra-articular injection of hyaluronate and corticosteroid. We hypothesized that this clinical superiority was due to intrinsic design characteristics of the RPD that permitted one-handed operation and enhanced control of the device by the operating physician. Materials and Methods Twenty physicians were tested for their ability to control a syringe and needle during a typical aspiration procedure with the RPD versus the traditional syringe using the validated quantitative needle-based displacement procedure model. Outcomes included unintended forward penetration (loss of control of the needle in the forward direction measured in mm), unintended retraction (loss of control of the needle in the reverse direction), and the ability to generate vacuum. Physicians operated the RPD with one hand and operated the traditional syringe alternatively with one hand and two hands. A nonoperating observer recorded all outcomes and measurements. Results The traditional syringe demonstrated a significant unintended forward penetration of 13.9 ± 2.3 mm (one-handed) and 9.02 ± 3.11 mm (two-handed). The RPD reduced unintended forward penetration to 7.39 ± 1.83 mm (a reduction of 47% and 18% respectively, p Conclusions The RPD with one hand generates vacuum more easily and is better controlled by physicians during typical interventional syringe procedures than the conventional syringe with one or two hands. The RPDs of all sizes are better controlled and superior to conventional syringes for typical interventional syringe procedures, including arthrocentesis and joint injection.

Severe acute inflammatory reaction (SAIR) of the fetlock joint after intraarticular hyaluronate injection in a horse

Hyaluronate (HA) was administered by intra-articular injection to a 13-year-old Haflinger mare for treatment of metacarpophalangeal osteoarthritis. Ten hours after the injection, a severe inflammatory reaction developed in the treated joint. While awaiting results of synovial fluid analysis, treatment for iatrogenic infectious arthritis was initiated, but the analysis did not confirm sepsis. Clinical signs improved significantly following systemic non-steroidal anti-inflammatory medication and the horse was discharged three days later. Following an intravenous hyaluronate injection, four days after discharge, the synovitis recurred. Synovial fluid analysis did not show any abnormalities, but the clinical signs were severe. The severe acute inflammatory reaction required systemic non-steroidal anti-inflammatory and intra-articular corticosteroid treatment in order to resolve the problem.

An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the knee

Five double-blind, randomized, saline-controlled trials (RCTs) were included in the United States marketing application for an intra-articular hyaluronan (IA-HA) product for the treatment of osteoarthritis (OA) of the knee. We report an integrated analysis of the primary Case Report Form (CRF) data from these trials. Trials were similar in design, patient population and outcome measures - all included the Lequèsne Algofunctional Index (LI), a validated composite index of pain and function, evaluating treatment over 3 months. Individual patient data were pooled; a repeated measures analysis of covariance was performed in the intent-to-treat (ITT) population. Analyses utilized both fixed and random effects models. Safety data from the five RCTs were summarized. A total of 1155 patients with radiologically confirmed knee OA were enrolled: 619 received three or five IA-HA injections; 536 received "placebo" saline injections. In the active and control groups, mean ages were 61.8 and 61.4 years; 62.4% and 58.8% were women; baseline total Lequèsne scores 11.03 and 11.30, respectively. Integrated analysis of the pooled data set found a statistically significant reduction (P < 0.001) in total Lequèsne score with hyaluronan (HA) (-2.68) vs placebo (-2.00); estimated difference -0.68 (95% CI: -0.56 to -0.79), effect size 0.20. Additional modeling approaches confirmed robustness of the analyses. This integrated analysis demonstrates that multiple design factors influence the results of RCTs assessing efficacy of intra-articular (IA) therapies, and that integrated analyses based on primary data differ from meta-analyses using transformed data.

Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interleukin-1β-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts via down-regulation of NF-κB and p38

In rheumatoid arthritis (RA), it is well known that rheumatoid synovial fibroblasts (RSF) produce matrix metalloproteinases (MMPs) when stimulated with proinflammatory cytokines such as interleukin-1beta (IL-1beta), which causes joint destruction. We have previously shown that hyaluronan (HA) inhibits IL-1beta actions in RSF via CD44, the principal HA receptor. However, CD44 mediates HA effects only partially, and intracellular events after the HA binding to its receptors remain unclear. We investigated the role of intercellular adhesion molecule-1 (ICAM-1), another cell surface receptor for HA, and the intracellular signalling pathways in the actions of HA. RSF were isolated from rheumatoid synovial tissues by enzymatic digestion and cultured in monolayers. The confluent cells were incubated for 48 h with IL-1beta, IL-1beta in the presence of HA, or IL-1beta in the presence of HA with pretreatment with anti-ICAM-1 antibody. Secretion of MMP-1 and MMP-3 was analysed by immunoblotting and immunofluorescence cytochemistry. Immunofluorescence cytochemistry was also performed to evaluate binding of HA to ICAM-1. The phosphorylation of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was analysed by immunoblotting. Production of MMP-1 and MMP-3 by RSF was stimulated by IL-1beta. HA at > or =2 mg/ml significantly inhibited MMP production induced by IL-1beta in a dose-dependent manner. Moreover, pretreatment with anti-ICAM-1 antibody at 50 mug/ml significantly blocked the effects of HA on the actions of IL-1beta on RSF, as shown by immunoblotting and immunofluorescence cytochemistry. Another immunofluorescence cytochemistry study demonstrated that HA bound RSF via ICAM-1. Inhibition studies revealed the requirement of NF-kappaB, p38 and c-jun NH2-terminal kinase (JNK) for IL-1beta-induced MMP production. IL-1beta activated all three pathways, whereas HA down-regulated their phosphorylation. Pretreatment with anti-ICAM-1 antibody reversed the inhibitory effects of HA on the activation of NF-kappaB and p38 without affecting JNK. HA suppresses IL-1beta-enhanced MMP-1 and MMP-3 synthesis in RSF via ICAM-1 through down-regulation of NF-kappaB and p38. Intra-articular injection of HA of high molecular weight may work through such a mechanism in RA joints.

Volume of a wash and the other conditions for maximum therapeutic effect of arthroscopic lavage in rheumatoid knees

The objective of this study was to determine the appropriate volume of saline to obtain a beneficial effect of arthroscopic lavage and the prognostic factors related to the clinical effect in a refractory rheumatoid knee. Arthroscopic lavage or arthrocentesis was performed in a random manner in 142 patients with relapsing rheumatoid arthritis. All patients were followed up for 24 months. Intra-articular lavage with 5 l (p < 0.01) or 3 l (p < 0.05) of saline gave better clinical results than did arthrocentesis. There was no significant difference between the cumulative incidence of recurrence of knee synovitis in patients who underwent arthrocentesis and that in patients who underwent lavage with 1 l of saline. Cox regression analysis showed that patients with knee arthritis of more than 6 months in duration and with Larsen grade II or less were more responsive to lavage with 5 or 3 l of saline. The duration of the effect of lavage with 3 l of saline was increased 2.9-fold (p = 0.04) by injection of both steroids and high molecular weight hyaluronan. No bleeding or infectious complications occurred after those procedures. Arthroscopic lavage with 5 l of saline is safe and has good therapeutic effects for rheumatoid knees with mild destruction in which arthritis has persisted for more than 6 months. Lavage with 3 l of saline is recommended when intra-articular injection of corticosteroid and high molecular weight hyaluronan is performed after lavage.

Septic knee arthritis after intra-articular hyaluronate injection: Two case reports

Intraarticular sodium hyaluronate injection to treat osteoarthritis is associated with minor side effects. Infections seem uncommon. We report two cases of septic knee arthritis. One patient was an 80-year-old woman who was admitted for Staphylococcus aureus knee arthritis after several intraarticular injections of sodium hyaluronate and corticosteroids. In the other patient, a 78-year-old woman, Neisseria mucosa knee arthritis occurred after a single sodium hyaluronate injection. Faultless aseptic technique is essential when administering hyaluronate viscosupplementation. Patients should be informed of the risk of septic arthritis.

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.

Effects of hyaluronan on three-dimensional microarchitecture of subchondral bone tissues in guinea pig primary osteoarthrosis

Hyaluronan (HA) has received increasing interest as a potential agent in therapeutic intervention in osteoarthrosis (OA). HA has been shown to reduce arthritic lesions in experimental animal models of articular cartilage injury. This study was to investigate the effects of high molecular weight HA intra-articular injection on subchondral bone tissues. Fifty-six male guinea pigs were randomly divided into 5 groups. During the initial 2.5-month period, three groups received intra-articular injection of HA 0.4 mg/kg/week for 5 weeks in both knee joints. Two control groups received vehicle. After 2.5 months, one HA group and one control group were sacrificed. The remaining 3 groups (5.5-month groups) were left for an additional 3 months before sacrifice during which time one HA group received additional 5 weeks injections, one HA group received no more injections, and the control group received vehicle. The left tibiae were harvested and micro-CT scanned to quantify three-dimensional microarchitecture of subchondral bone plate, cancellous bone and cortical bone, followed by mechanical testing and collagen and mineral determinations. All HA-treated groups had almost normal cartilage, whereas the control groups had typical OA-related cartilage degradation. In the 2.5-month group, HA resulted in significantly decreased subchondral plate volume fraction and thickness and HA-treated cancellous bone had significantly lower bone volume fraction, and typical rod-like structure. After 5.5 months, these changes were more pronounced, with an additional marked decrease in connectivity and bone surface density. HA-treated cortical bone had significantly greater volume fraction at both observation times. HA groups had greater bone mineral concentration and reduced collagen to mineral ratio with similar mechanical properties of cancellous bone but less stiff cortical bone. The effects of HA on cartilage and subchondral bone were maintained when treatment was discontinued. In summary, HA effectively protects against cartilage degeneration, decreases subchondral bone density and thickness, changes trabecular structure toward rod-like, so that subchondral bone becomes more compliant and thereby reduces cartilage stress during impact loading. HA preserved cancellous bone mechanical properties by increasing bone mineralization. Early HA administration is effective for intervention of OA initiation and progression, and short-term early HA treatment is sufficient to maintain treatment effects.