CHONDRO-PROTECTIVE AGENTS: GLYCOSAMINOGLYCANS & OTHER THINGS

MEDLINE SEARCH FEB 13 '95

"Chevallard M; Galanti A; Paresce E; Wolf A; Carrabba M Efficacy and tolerability of galactosamino-glycuronoglycan- sulfate in osteoarthritis of the knee: an 11-month experience. Osteoarthritis and Extra-articular Rheumatism Unit, G. Pini Orthopedic Institute, Milan, Italy. Int J Clin Pharmacol Res 1993;13 Suppl:49-53 Unique Identifier: MEDLINE 95088053

Abstract:

Chondroprotective agents represent a model for basic therapy of osteoarthritis (OA), thanks to their activity directed towards the protection and repair of articular cartilage. One of the most recent compounds capable of interfering with the pathogenic mechanisms of OA is galactosamino-glycuronoglycan-sulfate (GGGS), a highly depolymerized glycosaminoglycan with favorable chondroprotective and anti-inflammatory properties. The present paper describes the experience with GGGS given to a group of patients with symptomatic OA of the knee as compared to a parallel group treated with placebo. The drug (or placebo) was administered in two series of 25 intramuscular injections each over a period of 11 months, and four successive evaluations of treatment were made at various times during this period, and a fifth evaluation one month after the suspension of treatment to better evaluate the permanence of the therapeutic effect. The results obtained showed significant improvements on pain, algofunctional index and consumption of NSAIDs only in the group treated with GGGS. The drug was well tolerated and no reduction of dosage or drop-out from therapy were required. The favorable clinical effects and the patients' good compliance make GGGS a useful drug for successful chondroprotective treatment of OA.

Medical Subject Headings:

Aged Anti-Inflammatory Agents, Non-Steroidal--ADMINISTRATION & DOSAGE- -PHARMACOLOGY--*THERAPEUTIC USE *Cartilage, Articular--DRUG EFFECTS--PATHOLOGY Comparative Study Double-Blind Method Female *Glycosaminoglycans--ADMINISTRATION & DOSAGE--PHARMACOLOGY- -THERAPEUTIC USE Human Injections, Intramuscular *Knee Joint--DRUG EFFECTS--PATHOLOGY Longitudinal Studies Male Middle Age *Osteoarthritis--DRUG THERAPY Pain--DRUG THERAPY Pain Measurement CLINICAL TRIAL (Publ. Type) JOURNAL ARTICLE (Publ. Type) RANDOMIZED CONTROLLED TRIAL (Publ. Type)

Paroli E Glycosaminoglycan chondroprotection: pharmacological vistas. Institute of Pharmacology, University of Rome La Sapienza, Italy. REVIEW ARTICLE: 50 REFS. Int J Clin Pharmacol Res 1993;13 Suppl:1-9 Unique Identifier: MEDLINE 95088047

Abstract:

Chondroprotection is a somewhat new field in the therapy of osteoarthritis, which is designed to improve cartilage repair as well as enhance joint remodeling. It clearly results from both laboratory models as well as from studies on human osteoarthritis, that cartilage contains biological resources to meet the repair of degenerative injuries and inflammation. Interestingly, sulfated glycosaminoglycans from matrix inhibit leukocyte protease and complement-mediated immunological reactions. By fractioning cartilage glycosaminoglycans from Selachus (Matrix), evidence has been obtained that a proper chondroitinsulfate sequence, which is able to inhibit elastase, may be released from cartilage proteoglycans by cleavage of the xyl-ser O-glycosidic bond. Since a number of sulfated glycosaminoglycans have a regulatory function in an array of tissues, attention is drawn to possible regulatory properties of selected sequences of matrix chondroitinsulfate, as far as chondroprotection is concerned.

Medical Subject Headings:

Anti-Inflammatory Agents, Non-Steroidal--PHARMACOLOGY--THERAPEUTIC USE *Cartilage--DRUG EFFECTS--PATHOLOGY Chondroitin Sulfates--PHARMACOLOGY--THERAPEUTIC USE Comparative Study *Glycosaminoglycans--PHARMACOLOGY--THERAPEUTIC USE Heparin--PHARMACOLOGY--THERAPEUTIC USE Human Hyaluronidase--ANTAGONISTS & INHIB *Osteoarthritis--DRUG THERAPY Pancreatopeptidase--ANTAGONISTS & INHIB Protease Inhibitors--PHARMACOLOGY--THERAPEUTIC USE CLINICAL TRIAL (Publ. Type) JOURNAL ARTICLE (Publ. Type) REVIEW (Publ. Type) REVIEW, TUTORIAL (Publ. Type)

Todhunter RJ; Lust G Polysulfated glycosaminoglycan in the treatment of osteoarthritis. Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. REVIEW ARTICLE: 55 REFS. J Am Vet Med Assoc 1994 Apr 15;204(8):1245-51 Unique Identifier: MEDLINE 94284158

Medical Subject Headings:

Animal Disease Models, Animal Enzyme Inhibitors *Glycosaminoglycans--THERAPEUTIC USE Human *Osteoarthritis--DRUG THERAPY--PREVENTION & CONTROL--VETERINARY JOURNAL ARTICLE (Publ. Type) REVIEW (Publ. Type) REVIEW, TUTORIAL (Publ. Type)

Goa KL; Benfield P Hyaluronic acid. A review of its pharmacology and use as a surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing. Adis International Limited, Auckland, New Zealand. REVIEW ARTICLE: 256 REFS. Drugs 1994 Mar;47(3):536-66 Unique Identifier: MEDLINE 94252210

Abstract:

Hyaluronic acid is a naturally occurring polysaccharide with distinct physicochemical properties which underlie its application as a viscoelastic tool in ophthalmological surgery. In cataract surgery the role of hyaluronic acid in facilitating procedures and protecting the corneal endothelium is well established. Some benefit has also been gained with the use of hyaluronic acid in penetrating keratoplasty, trabeculectomy, retinal reattachment and trauma surgery, although its efficacy in these indications is less well-defined in the published literature. In addition to its lubricating and cushioning properties, demonstration of some in vitro anti-inflammatory activity and a possible disease-modifying effect for hyaluronic acid in animals has prompted its investigation as a treatment in osteoarthritis and, to a much lesser extent, in rheumatoid arthritis. Hyaluronic acid 20 mg, as weekly intra-articular injections for 3 to 7 weeks, improved knee pain and joint motion in patients with osteoarthritis. Although this occurred to a greater degree than with placebo in most comparisons, the effects of hyaluronic acid was similar to those of placebo in the largest trial. In the few available comparisons with other agents, hyaluronic acid appeared equivalent to methylprednisolone 40 mg (for 3 weeks) and to a single injection of triamcinolone 40 mg. Hyaluronic acid was distinguished from other therapies by providing a sustained effect after treatment discontinuation. Together with its very good tolerability profile, these properties justify further study of hyaluronic acid in patients with osteoarthritis. Some limited evidence of improvement in patients with rheumatoid arthritis, and a possible healing effect of hyaluronic acid on tympanic membrane perforations, represent additional areas of interest for future investigation. In summary, hyaluronic acid is a well-established adjunct to cataract surgery and may prove to be a promising option in the treatment of patients with osteoarthritis. Its very good tolerability provides further impetus for examination of its potential role in an extended scope of arthritic and ophthalmological indications, and in wound healing.

Medical Subject Headings:

Adjuvants, Pharmaceutic Animal *Cataract Extraction Endothelium, Corneal--DRUG EFFECTS Human *Hyaluronic Acid--PHARMACOLOGY--PHARMACOKINETICS--THERAPEUTIC USE Ophthalmology *Osteoarthritis--DRUG THERAPY *Wound Healing--DRUG EFFECTS JOURNAL ARTICLE (Publ. Type) REVIEW (Publ. Type) REVIEW, ACADEMIC (Publ. Type)

Keller WG; Aron DN; Rowland GN; Odend'hal S; Brown J The effect of trans-stifle external skeletal fixation and hyaluronic acid therapy on articular cartilage in the dog. Department of Small Animal Medicine, Avian Medicine, Anatomy and Radiology, College of Veterinary Medicine, University of Georgia, Athens. Vet Surg 1994 Mar-Apr;23(2):119-28 Unique Identifier: MEDLINE 94249163

Abstract:

Transarticular external skeletal (TES) fixators were applied unilaterally to the stifle joints of 10 young adult dogs. After 4 weeks, the fixators were removed from all dogs. Two dogs were not allowed a remobilization period, whereas 8 dogs were provided with 4 additional weeks of weight-bearing activity in a kennel run. Four dogs were given high-molecular weight hyaluronic acid by intra-articular injection weekly during the remobilization period. Clinical gait evaluations and range of motion were determined during the remobilization period. Articular cartilage samples from both stifle joints of all dogs were evaluated histologically and histochemically. No significant differences in gait scores or range of motion were noted between treated and untreated dogs. Articular cartilage proteoglycan content was reduced after 4 weeks of trans-stifle external skeletal fixation as determined by loss of alcian blue (AB) histochemical staining. Improved homogeneity of histochemical staining was observed after remobilization. However, remobilization was associated with histological damage to the surface and tangential layers of articular cartilage. Remobilization combined with hyaluronic acid (HA) therapy improved histochemical staining and reduced structural damage to articular cartilage when compared with remobilization alone.

Medical Subject Headings:

Animal *Cartilage, Articular--CHEMISTRY--DRUG EFFECTS--PATHOLOGY *Dogs--SURGERY *External Fixators--ADVERSE EFFECTS--VETERINARY Histocytochemistry *Hyaluronic Acid--PHARMACOLOGY--THERAPEUTIC USE Immobilization Male Proteoglycans--ANALYSIS--METABOLISM Random Allocation *Stifle Support, Non-U.S. Gov't JOURNAL ARTICLE (Publ. Type)

Aviad AD; Houpt JB The molecular weight of therapeutic hyaluronan (sodium hyaluronate): how significant is it? Rheumatic Disease Unit, Mount Sinai Hospital, University of Toronto, ON, Canada. REVIEW ARTICLE: 56 REFS. J Rheumatol 1994 Feb;21(2):297-301 Unique Identifier: MEDLINE 94238575

Abstract:

Various molecular weight hyaluronic acid (HA) preparations have been injected into joints for the treatment of human and equine osteoarthritis. A therapeutic advantage has been claimed for commercial products with a molecular weight in the range found in normal synovial fluid (SF), compared to lower molecular weight products. But a correlation between molecular weight and efficacy is not borne out by an analysis of the available literature on clinical results. SF viscosity, HA concentration, HA molecular weight and rate of synthesis in joint disease. It is proposed that the beneficial effect of injected HA in joint disease may be due to pharmacological rather than to physical properties.

Medical Subject Headings:

Animal Horse Diseases--DRUG THERAPY Horses Human *Hyaluronic Acid--CHEMISTRY--THERAPEUTIC USE *Joint Diseases--DRUG THERAPY--VETERINARY Molecular Weight Osteoarthritis--DRUG THERAPY--VETERINARY Synovial Fluid--DRUG EFFECTS--PHYSIOLOGY Viscosity JOURNAL ARTICLE (Publ. Type) REVIEW (Publ. Type) REVIEW, TUTORIAL (Publ. Type)

Ghosh P The role of hyaluronic acid (hyaluronan) in health and disease: interactions with cells, cartilage and components of synovial fluid. Raymond Purves Bone & Joint Research Laboratories, University of Sydney, Royal North Shore Hospital of Sydney, St. Leonards, NSW, Australia. REVIEW ARTICLE: 72 REFS. Clin Exp Rheumatol 1994 Jan-Feb;12(1):75-82 Unique Identifier: MEDLINE 94215255

Abstract:

Intra-articular administration of hyaluronic acid (Hyaluronan) (HA) is now gaining widespread acceptance for the treatment of osteoarthritis (OA), even though little is known of its mechanism of action. In vitro and in vivo studies have shown that HA is able to modulate a variety of cellular functions, suppress the activities of pro-inflammatory mediators and can attenuate the nociceptive response in arthritic joints. However, recent studies with animal models of non-inflammatory OA have questioned the ability of HA to protect articular cartilage degeneration directly. The objective of this review is to examine some aspects of HA chemistry and pharmacology in relation to its interactions with cells, cartilage and the components of synovial fluid.

Medical Subject Headings:

Analgesics--PHARMACOLOGY Animal Anti-Inflammatory Agents, Non-Steroidal--PHARMACOLOGY *Cartilage, Articular--CYTOLOGY--METABOLISM Human *Hyaluronic Acid--PHARMACOLOGY--PHYSIOLOGY--THERAPEUTIC USE *Osteoarthritis--DRUG THERAPY--METABOLISM Rabbits Sheep *Synovial Fluid--CYTOLOGY--METABOLISM JOURNAL ARTICLE (Publ. Type) REVIEW (Publ. Type) REVIEW, TUTORIAL (Publ. Type)

Skakibara Y; Miura T; Iwata H; Kikuchi T; and others Effect of high-molecular-weight sodium hyaluronate on immobilized rabbit knee. Department of Orthopedic Surgery, Tokyo Kouseinenkin Hospital, Japan. Clin Orthop 1994 Feb;(299):282-92 Unique Identifier: MEDLINE 94163864

Abstract:

Experimental osteoarthrosis of the knee joint was induced in rabbits using a polyethylene binding brace. A 1% solution of sodium hyaluronate (HA) of molecular weight 1.73 x 10(6) (HA-173) was administered intraarticularly at a dosage of 0.1 ml/kg body weight twice a week. Changes in articular cartilage and synovial membrane, and joint contracture were compared with a saline control group at intervals throughout a six-week period of immobilization. In all groups, articular cartilage degeneration and joint contracture progressed with time but were inhibited by the administration of HA-173. Additionally, the results of a 1% solution of HA of molecular weight 9.8 x 10(5) (HA-98), a 1% solution of HA of molecular weight 2.02 x 10(6) (HA-202), and saline, each administered twice a week for five weeks at a dose of 0.1 ml/kg body weight, were compared. It was clear that the articular cartilage degeneration was significantly inhibited by HA as compared with saline, and that the effect was more potent with the higher molecular weight, HA-202, than with HA-98. Furthermore, joint contracture was inhibited by HA, and the effect was more potent with the higher molecular weight, HA-202, than with HA-98.

Medical Subject Headings:

Animal Braces Cartilage, Articular--DRUG EFFECTS--PATHOLOGY Comparative Study Disease Models, Animal Drug Screening *Hyaluronic Acid--THERAPEUTIC USE Immobilization *Knee Joint--DRUG EFFECTS--PATHOLOGY Male Molecular Weight Osteoarthritis--DRUG THERAPY--ETIOLOGY--PATHOLOGY Polyethylenes Rabbits Synovial Membrane--DRUG EFFECTS--PATHOLOGY Time Factors JOURNAL ARTICLE (Publ. Type)

Yoshimi T; Kikuchi T; Obara T; Yamaguchi T; and others Effects of high-molecular-weight sodium hyaluronate on experimental osteoarthrosis induced by the resection of rabbit anterior cruciate ligament. Department of Orthopedics, Tokyo Koseinenkin Hospital, Japan. Clin Orthop 1994 Jan;(298):296-304 Unique Identifier: MEDLINE 94163822

Abstract:

Sodium hyaluronate (HA) with a molecular weight of 202 x 10(4) (HA-202) was administered into the right knees of mature rabbits for the treatment of experimental osteoarthrosis induced by resection of the anterior cruciate ligament. At six and 12 weeks after the initiation of administration, the test group was compared with a group administered physiological saline solution to determine the effects on articular cartilage and synovial tissue. In both the six- and the 12-week period, cartilage degeneration proceeded with the lapse of time in both groups; however at 12 weeks, the efficacy of HA-202 in inhibiting degeneration was clearly observed at the lateral condyle of the femur and tibia where relatively marked degeneration was observed in the saline group. A comparison was also made among three groups administered HA-95 (sodium hyaluronate with a molecular weight of 95 x 10(4)), HA-202, and saline, respectively, for 12 weeks. The saline group showed the greatest cartilage degeneration accompanied by complete disorganization of the cartilage layer and the disappearance of chondrocytes. The degeneration was less in the HA groups, and it was more significantly inhibited in the HA-202 group than in the HA-95 group.

Medical Subject Headings:

Animal Anterior Cruciate Ligament--SURGERY Cartilage, Articular--DRUG EFFECTS Comparative Study Femur--PATHOLOGY *Hyaluronic Acid--THERAPEUTIC USE Knee Joint Male Molecular Weight *Osteoarthritis--DRUG THERAPY--PHYSIOPATHOLOGY Rabbits Synovial Membrane--DRUG EFFECTS Tibia--PATHOLOGY JOURNAL ARTICLE (Publ. Type)

Graf J; Neusel E; Schneider E; Niethard FU Intra-articular treatment with hyaluronic acid in osteoarthritis of the knee joint: a controlled clinical trial versus mucopolysaccharide polysulfuric acid ester. Orthopedic University Hospital Heidelberg, Department of Experimental Orthopedics, Germany. Clin Exp Rheumatol 1993 Jul-Aug;11(4):367-72 Unique Identifier: MEDLINE 94007366

Abstract:

In a single-blind, randomized clinical trial, both the efficacy and safety of hyaluronic acid (HA) were compared with that of mucopolysaccharide polysulfuric acid ester (MPA) in patients with osteoarthritis of the knee joint. Both agents were administered intra-articularly over six weeks. Patients received either seven injections of HA or 13 injections of MPA. Joint function, range of motion, severity of pain, the general condition of the bony structure and soft tissue of the joint area, and the global clinical efficacy and safety of the medication were assessed. The mean improvement in the modified total Larson rating score was 22% (SD = 28) after HA treatment and 7% (SD = 17) after treatment with MPA (analysis of variance: p = 0.02). This change was mainly caused by a reduction of pain. The onset of pain relief was more rapid in the HA group. The therapeutic effect increased in both treatment groups during the follow-up period. During this interval, lasting six months after the start of treatment, a further reduction of pain and an improvement of knee joint function could be observed. At the end of the study, 25 out of 33 (76%) patients in the HA group and 11 out of 24 (46%) patients in the MPA group were symptom-free or markedly improved (Chi-square test: p = 0.02). Both agents were tolerated very well.

Medical Subject Headings:

Adult Aged Comparative Study Drug Tolerance Female *Glycosaminoglycans--ADMINISTRATION & DOSAGE--ADVERSE EFFECTS- -THERAPEUTIC USE Human *Hyaluronic Acid--ADMINISTRATION & DOSAGE--ADVERSE EFFECTS- -THERAPEUTIC USE Injections, Intra-Articular Male Middle Age *Osteoarthritis--DRUG THERAPY Safety CLINICAL TRIAL (Publ. Type) JOURNAL ARTICLE (Publ. Type) RANDOMIZED CONTROLLED TRIAL (Publ. Type)

Yu LP Jr; Smith GN Jr; Brandt KD; Myers SL; and others Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline [see comments] Rheumatology Division, Indiana University School of Medicine, Indianapolis 46202-5103. Arthritis Rheum 1992 Oct;35(10):1150-9 Unique Identifier: MEDLINE 93038896 Comment in: Arthritis Rheum 1993 Sep;36(9):1335-6

Abstract:

OBJECTIVE. In vitro studies have indicated that levels of neutral metalloproteinases in osteoarthritic (OA) cartilage are elevated and that doxycycline (doxy) inhibits collagenolytic and gelatinolytic activity in extracts of OA cartilage. The purpose of the present study was to test the effect of oral doxy administration on the severity of cartilage degeneration in OA. METHODS. OA was induced in 12 adult mongrel dogs by transection of the anterior cruciate ligament (ACL) 2 weeks after dorsal root ganglionectomy. Six dogs received doxy orally from the day after ACL transection until they were killed 8 weeks later; the other 6 served as untreated OA controls. RESULTS. The unstable knee of each untreated dog exhibited extensive full-thickness cartilage ulceration of the medial femoral condyle. In sharp contrast, cartilage on the distal aspect of the femoral condyle of the unstable knee was grossly normal in 2 doxy-treated dogs, and exhibited only thinning and/or surface irregularity in the others. Degenerative cartilage lesions on the medial trochlear ridge, superficial fibrillation of the medial tibial plateau, and osteophytosis were, however, unaffected by doxy treatment. Collagenolytic activity and gelatinolytic activity in cartilage extracts from OA knees of untreated dogs were 5-fold and 4-fold greater, respectively, than in extracts from dogs given doxy. CONCLUSION. Prophylactic administration of doxy markedly reduced the severity of OA in weight-bearing regions of the medial femoral condyle. It remains to be determined whether administration of doxy after OA changes have developed is also effective.

Medical Subject Headings:

Administration, Oral Animal Cartilage, Articular--DRUG EFFECTS--METABOLISM--PATHOLOGY Collagenases--ANTAGONISTS & INHIB Dogs *Doxycycline--ADMINISTRATION & DOSAGE--THERAPEUTIC USE Gait Glycosaminoglycans--BIOSYNTHESIS *Osteoarthritis--METABOLISM--PATHOLOGY--PREVENTION & CONTROL Pepsin A--ANTAGONISTS & INHIB Support, U.S. Gov't, P.H.S. Synovial Fluid--METABOLISM Tissue Culture Uronic Acids--METABOLISM JOURNAL ARTICLE (Publ. Type)

Dragani L; D'Aurelio A; Vecchiet L [Effects of a heparin-heparinoid combination on esthesiologic and trophic changes in deep periarticular tissues in gonarthritis] Cattedra di Semeiotica Medica, Universita degli Studi G. D'Annunzio, Chieti. Language: Ita Riv Eur Sci Med Farmacol 1992 Jul-Aug;14(4):271-7 Unique Identifier: MEDLINE 93303369

Abstract:

We evaluated the efficacy of heparin-glucuronylglucosaminoglycane association topically used on periarticular deep tissues (subcutaneous and muscle), in 20 females divided into two homogeneous groups of 10 each, affected by painful osteoarthritis of the knee. Electrically stimulated subcutaneous and muscular pain thresholds have been assessed; ultrasound scan of subcutaneous tissue overlying articular rima and vastus medialis muscle, and ultrasound scan of vastus medialis muscle thickness have been also examined. The measurements have been done (at the beginning of the experiment) in basal conditions and respectively after one, two, and three weeks treatment with the drug or placebo administered in a double blind fashion. Subcutaneous and muscular pain thresholds have shown an important rise right from the first week of treatment; subcutaneous tissue thickness was significantly decreased after two weeks treatment and in the same period a significant increase of vastus medialis muscle was registered. No such variations have been shown after placebo treatment. The possible mechanisms of such effects have been assessed in a peripheral control action of inflammation, with decrease of nociceptive message and consequent limitation of dystrophic reflex phenomena.

Medical Subject Headings:

Aged Drug Combinations English Abstract Female *Glycosaminoglycans--THERAPEUTIC USE *Heparin--THERAPEUTIC USE Human Middle Age *Osteoarthritis--COMPLICATIONS--DRUG THERAPY--ULTRASONOGRAPHY Pain Threshold--DRUG EFFECTS JOURNAL ARTICLE (Publ. Type)

Ghosh P; Armstrong S; Read R; Numata Y; and others Animal models of early osteoarthritis: their use for the evaluation of potential chondroprotective agents. Raymond Purves Research Laboratories, University of Sydney, Royal North Shore Hospital of Sydney, St. Leonards, New South Wales, Australia. Agents Actions Suppl 1993;39:195-206 Unique Identifier: MEDLINE 93206713

Abstract:

Medial meniscectomy was undertaken in adult merino sheep and after 16 weeks exercise each group was administered five weekly intra-articular injections of saline, pentosan polysulphate (PPS), hyaluronic acid (HA) or a combination of PPS + HA. Gait analysis and x-rays were undertaken before and after drug treatment. At sacrifice (26 weeks), joints were examined for gross pathological and histochemical changes. Only the PPS-treated group showed an improvement in gait, with low radiological and histology scores. The HA-treated group showed similar but less significant changes to these parameters.

Medical Subject Headings:

Animal Arthrography Cartilage, Articular--PATHOLOGY--RADIOGRAPHY Disease Models, Animal Exertion Gait--PHYSIOLOGY Histocytochemistry *Hyaluronic Acid--ADMINISTRATION & DOSAGE--THERAPEUTIC USE Injections, Intra-Articular Joints--PATHOLOGY Male *Osteoarthritis--DRUG THERAPY--PATHOLOGY--RADIOGRAPHY *Pentosan Sulfuric Polyester--ADMINISTRATION & DOSAGE--THERAPEUTIC USE Sheep Synovial Membrane--PHYSIOLOGY JOURNAL ARTICLE (Publ. Type)

Bertolami CN; Gay T; Clark GT; Rendell J; and others Use of sodium hyaluronate in treating temporomandibular joint disorders: a randomized, double-blind, placebo-controlled clinical trial.

Section of Oral and Maxillofacial Surgery, University of California, School of Dentistry, Los Angeles 90024-1668. J Oral Maxillofac Surg 1993 Mar;51(3):232-42 Unique Identifier: MEDLINE 93187731

Abstract:

This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporomandibular joint (TMJ) disorders. One hundred twenty-one patients were studied at three test sites using a randomized, double-blind, placebo-controlled experimental design. Patients were selected on the basis of 1) confirmed diagnosis of either degenerative joint disease (DJD), reducing displaced disc (DDR), or non-reducing displaced disc (DDN); 2) non-responsiveness to non-surgical therapies; and 3) severe dysfunction as established by the Helkimo indices (HI), visual analog scales (VASs), and physical measurements of joint movement and joint noise (arthrophonometry [APM]). Subjects received a unilateral upper joint space injection of either 1) 1% sodium hyaluronate in physiologic saline (MedChem Products, Woburn, MA) or 2) USP physiologic saline. Clinical evaluations were performed using HI, VAS, and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection. Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval. For DJD, no difference in outcome was seen between treatment groups. For DDN, significant between-group differences were seen through 1 month; however, beyond this time point, the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy. For DDR, statistically significant within-group and between-group improvement in all three measures (HI, VAS, APM) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period. At the month-2 and month-3 examination intervals, twice as many patients treated with hyaluronate (90%) showed improvement compared to patients given placebo. Further, only 3% of patients with DDR who were treated with hyaluronate relapsed compared with 31% of patients with DDR given placebo.

Medical Subject Headings:

Adult Cartilage, Articular--PATHOLOGY--PHYSIOPATHOLOGY Dislocations--DRUG THERAPY--PHYSIOPATHOLOGY Double-Blind Method Facial Pain--DRUG THERAPY--PHYSIOPATHOLOGY--PSYCHOLOGY Female Human *Hyaluronic Acid--ADMINISTRATION & DOSAGE--ADVERSE EFFECTS- -THERAPEUTIC USE Injections, Intra-Articular Male Movement Osteoarthritis--DRUG THERAPY--PHYSIOPATHOLOGY Patient Satisfaction Placebos Prospective Studies Self Concept Sound Support, Non-U.S. Gov't *Temporomandibular Joint Diseases--DRUG THERAPY--PHYSIOPATHOLOGY- -PSYCHOLOGY Time Factors CLINICAL TRIAL (Publ. Type) JOURNAL ARTICLE (Publ. Type) MULTICENTER STUDY (Publ. Type) RANDOMIZED CONTROLLED TRIAL (Publ. Type)

Mazieres B; Loyau G; Menkes CJ; Valat JP; and others [Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis. 5-months result of a multicenter double-blind controlled prospective study using placebo] Centre Hospitalier Universitaire, Toulouse. Language: Fre Rev Rhum Mal Osteoartic 1992 Jul-Sep;59(7-8):466-72 Unique Identifier: MEDLINE 93134315

Abstract:

One hundred twenty patients with osteoarthritis of the knees and hips were entered into a randomized, placebo-controlled, double-blind trial designed to evaluate the effectiveness of chondroitin sulfate (Structum). The three-month treatment phase was followed by a two-month treatment-free phase to allow evaluation of carry-over effects. The main endpoint was use of non-steroidal anti-inflammatory drugs (expressed as mg of diclofenac equivalent). At completion of the three-month treatment phase, patients taking chondroitin sulfate (4 capsules/day) were using significantly less NSAIDs; this decrease persisted throughout the two-month treatment-free follow-up phase. The other parameters studied including visual analog scale assessment of pain, the Lequesne pain-function index, and overall patient and physician assessments, all showed a similar significant tendency. Tolerance was outstanding and no patients required premature withdrawal. These findings indicate that chondroitin sulfate is useful for the treatment of osteoarthritis, both as an agent slowly effective against symptoms and to reduce the need for NSAIDs. The carry-over effect of the drug suggests that intermittent administration may be appropriate.

Medical Subject Headings:

*Chondroitin Sulfates--THERAPEUTIC USE Double-Blind Method English Abstract Female Human *Knee Male Middle Age *Osteoarthritis--DRUG THERAPY--EPIDEMIOLOGY *Osteoarthritis, Hip--DRUG THERAPY--EPIDEMIOLOGY Placebos Prospective Studies CLINICAL TRIAL (Publ. Type) JOURNAL ARTICLE (Publ. Type) MULTICENTER STUDY (Publ. Type) RANDOMIZED CONTROLLED TRIAL (Publ. Type)

Tsvetkova ES; Agababova ER; Bogomolova NA [Cartilage-protective preparations in the therapy of osteoarthrosis] Language: Rus Ter Arkh 1992;64(5):59-60 Unique Identifier: MEDLINE 93088232

Abstract:

Based on an analysis of the current data on the pathogenesis of osteoarthrosis, the authors provide evidence for the importance of chondroprotective therapy. Present comparative experimental and clinical (tentative) data on the efficacy of chondroprotective drugs.

Medical Subject Headings:

Anti-Inflammatory Agents, Non-Steroidal--THERAPEUTIC USE *Cartilage, Articular--DRUG EFFECTS Chondroitin Sulfates--THERAPEUTIC USE Comparative Study English Abstract Glucosamine--THERAPEUTIC USE Human *Osteoarthritis--DRUG THERAPY--ETIOLOGY Tissue Extracts--THERAPEUTIC USE CLINICAL TRIAL (Publ. Type) JOURNAL ARTICLE (Publ. Type) RANDOMIZED CONTROLLED TRIAL (Publ. Type)

Agrati AM; Frigerio S; Palmieri G; Palmieri R; Vargiu A [The possible effects of galactosaminoglucuronoglycan sulfate on blood coagulation processes] II Divisione Medicina Generale Brera, Ospedale Niguarda- Ca Granda, Milano. Language: Ita Minerva Med 1992 Sep;83(9):529-31 Unique Identifier: MEDLINE 93063998

Abstract:

Ten patients with osteoarthritis were treated in an open study with galactosaminoglucuronoglycan sulphate for 60 days (800 mg b.i.d. per os). The following haemostatic indices were measured before and after treatment: platelet count, adhesion and aggregation; prothrombin time and activity; partial thromboplastin time and antithrombin III. Total and HDL cholesterolemia, triglycerides, arterial pressure and heart rate were also measured. No blood coagulation index was found to be significantly altered in treated patients. In addition, neither variations from the normal limits of lipidemic and cardiocirculatory values nor adverse effects related to treatment were reported. Although the study was carried out in a limited population, these findings show that GGG does not interfere with the coagulation process and, from a more general point of view, they confirm its excellent tolerance.

Medical Subject Headings:

Adult *Anticoagulants--THERAPEUTIC USE *Blood Coagulation--DRUG EFFECTS Blood Coagulation Tests *Chondroitin Sulfates--THERAPEUTIC USE Comparative Study English Abstract Human Osteoarthritis--BLOOD--DRUG THERAPY *Polysaccharides--THERAPEUTIC USE CLINICAL TRIAL (Publ. Type) JOURNAL ARTICLE (Publ. Type)

Pinals RS Pharmacologic treatment of osteoarthritis. Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick. REVIEW ARTICLE: 50 REFS. Clin Ther 1992 May-Jun;14(3):336-46; discussion 335 Unique Identifier: MEDLINE 92346652

Abstract:

Current pharmacotherapy for osteoarthritis (OA) is aimed at relief of pain and functional disability. Although an inflammatory component may be found in some cases, there is little evidence that anti-inflammatory drugs commonly used in the treatment of OA provide more relief than simple analgesics. A growing body of knowledge about the pathophysiology of OA now offers opportunities to develop interventions aimed at retarding the progressive degeneration of articular cartilage. This is a function of an imbalance between cartilage matrix synthesis and breakdown. New and experimental treatments include oral, parenteral, and intra-articular agents, some of which are chemicals and others biological products. Their modes of action have generally not been established in humans, but may be inferred from in vitro culture systems and animal models. These mechanisms include inhibition of synovial cell-derived cytokines and chondrocyte-derived degradative enzymes, inactivation of superoxide free radicals, stimulation of matrix synthesis, and enhancement of synovial fluid lubrication. Many of these treatments have been shown to provide short- or long-term symptomatic improvement in clinical trials. Protection of cartilage or promotion of repair has been demonstrated in animal studies, but not convincingly in human OA studies.

Medical Subject Headings:

Acetaminophen--THERAPEUTIC USE Analgesics--THERAPEUTIC USE Anti-Inflammatory Agents, Non-Steroidal--THERAPEUTIC USE Glycosaminoglycans--METABOLISM--THERAPEUTIC USE Human Hyaluronic Acid--THERAPEUTIC USE *Osteoarthritis--DRUG THERAPY--PHYSIOPATHOLOGY Salicylates--THERAPEUTIC USE Superoxide Dismutase--THERAPEUTIC USE Tissue Extracts--THERAPEUTIC USE JOURNAL ARTICLE (Publ. Type) REVIEW (Publ. Type) REVIEW, TUTORIAL (Publ. Type)

Carroll GJ; Bell MC; Laing BA; McCappin S; and others Reduction of the concentration and total amount of keratan sulphate in synovial fluid from patients with osteoarthritis during treatment with piroxicam. Department of Rheumatic Diseases, Royal Perth Hospital, Western Australia. Ann Rheum Dis 1992 Jul;51(7):850-4 Unique Identifier: MEDLINE 92337444

Abstract:

To study the effects of piroxicam on cartilage metabolism in vivo, a three phase (placebo/piroxicam 20 mg/day by mouth/placebo) double blind controlled trial was conducted in patients with osteoarthritis of the knee joint. Twenty one patients were recruited, 19 of whom (11 women, eight men, median age 70 years) completed the treatment schedule. The knee joint under study was aspirated to dryness at four week intervals. Treatment with piroxicam was accompanied by a decrease in the pain score, an improvement in the functional index, and an increased range of movement. Reductions in the concentration (mean (SEM) 120 (6) to 110 (8) micrograms/ml) and the total amount (1.22 (0.34) to 0.99 (0.37) mg) of keratan sulphate, but not the effusion volume (9.4 (2.5) to 8.3 (2.6) ml) were observed during treatment with piroxicam. These findings are consistent with decreased proteoglycan catabolism during treatment with piroxicam. Neither depressed synthesis nor enhanced clearance of degraded proteoglycan fragments can be excluded, however.

Medical Subject Headings:

Adolescence Adult Aged 80 and over Double-Blind Method Female Human *Keratan Sulfate--ANALYSIS--METABOLISM Knee Joint--PHYSIOPATHOLOGY Male Middle Age *Osteoarthritis--DRUG THERAPY--METABOLISM--PHYSIOPATHOLOGY *Piroxicam--THERAPEUTIC USE Proteoglycans--METABOLISM Support, Non-U.S. Gov't *Synovial Fluid--CHEMISTRY CLINICAL TRIAL (Publ. Type) JOURNAL ARTICLE (Publ. Type) RANDOMIZED CONTROLLED TRIAL (Publ. Type)"

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