Oral administration of polymer hyaluronic acid alleviates symptoms of knee osteoarthritis: a double-blind, placebo-controlled study over a 12-month period

Toshiyuki Tashiro, Satoshi Seino, Toshihide Sato, Ryosuke Matsuoka, Yasunobu Masuda, Naoshi Fukui, Toshiyuki Tashiro, Satoshi Seino, Toshihide Sato, Ryosuke Matsuoka, Yasunobu Masuda, Naoshi Fukui

Abstract

This study was conducted to investigate the efficacy of oral hyaluronic acid (HA) administration for osteoarthritis (OA) in knee joints. Sixty osteoarthritic subjects (Kellgren-Lawrence grade 2 or 3) were randomly assigned to the HA or placebo group. The subjects in the HA group were given 200 mg of HA once a day everyday for 12 months, while the subjects in the placebo group were given placebo. The subjects in both groups were requested to conduct quadriceps strengthening exercise everyday as part of the treatment. The subjects' symptoms were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM) score. The symptoms of the subjects as determined by the JKOM score improved with time in both the HA and placebo groups. This improvement tended to be more obvious with the HA group, and this trend was more obvious with the subjects aged 70 years or less. For these relatively younger subjects, the JKOM score was significantly better than the one for the placebo group at the 2nd and 4th months after the initiation of administration. Oral administration of HA may improve the symptoms of knee OA in patients aged 70 years or younger when combined with the quadriceps strengthening exercise.

Figures

Figure 1
Figure 1
Change in JKOM score with respect to subject's age. Subjects were divided into two groups of younger (≦70 years of age; 21 subjects) and older subjects (older than 70 years of age; 17 subjects), and change of JKOM score was evaluated in the respective groups. For younger subjects, change rate of total score relative to that at baseline (a) is shown together with rates for “pain and stiffness in the knees” (b), “condition of daily life” (c), “general activities” (d), and “health conditions” subscales (e). Change rates of total JKOM score and those of 4 subscales for older subjects are shown in the same manner (f–j, resp.). Open and closed circles indicate change rates of subjects given HA and placebo, respectively. Results are mean ± SE of 7 to 11 subjects. *P < 0.05 against baseline and #P < 0.05 against placebo group.
Figure 2
Figure 2
Change in JKOM score with respect to disease severity. Subjects were divided by the Kellgrel-Lawrence (K/L) grade determined on radiographs, and changes in the total JKOM score are shown in respective groups by change rates relative to scores at baseline. Results of subjects with K/L grade 2 knee OA (A) and those with K/L grade 3 OA (B) are shown. Open and closed circles indicate change rates of subjects given HA and placebo, respectively. Results are mean ± SE of 9 to 11 subjects. *P < 0.05 against baseline.

References

    1. Loeser RF., Jr. Aging and the etiopathogenesis and treatment of osteoarthritis. Rheumatic Disease Clinics of North America. 2000;26(3):547–567.
    1. Murphy L, Schwartz TA, Helmick CG, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Care and Research. 2008;59(9):1207–1213.
    1. Jinks C, Jordan K, Croft P. Osteoarthritis as a public health problem: the impact of developing knee pain on physical function in adults living in the community: (KNEST 3) Rheumatology. 2007;46(5):877–881.
    1. Oliveria SA, Felson DT, Reed JI, Cirillo PA, Walker AM. Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization. Arthritis and Rheumatism. 1995;38(8):1134–1141.
    1. Centers for Disease Control and Prevention. Prevalence of arthritis-United States. Morbidity and Mortality Weekly Report. 1997;50:334–336.
    1. Mayer K, Palemer J. The polysaccharide of the vitreous humor. Journal of Biological Chemistry. 1934;107:629–637.
    1. Peyron JG, Balazs EA. Preliminary clinical assessment of Na-hyaluronate injection into human arthritic joints. Pathologie Biologie. 1974;22(8):731–736.
    1. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis and Rheumatism. 2000;43(9):1905–1915.
    1. Day R, Brooks P, Conaghan PG, Petersen M. A double blind, randomized, multicenter, parallel group study of the effectiveness and tolerance of intraarticular hyaluronan in osteoarthritis of the knee. Journal of Rheumatology. 2004;31(4):775–782.
    1. Adams ME, Lussier AJ, Peyron JG. A risk-benefit assessment of injections of hyaluronan and its derivatives in the treatment of osteoarthritis of the knee. Drug Safety. 2000;23(2):115–130.
    1. Sato T, Iwaso H. An effectiveness study of hyaluronic acid (Hyabest J) in the treatment of osteoarthritis of the knee. Journal of New Remedies and Clinics. 2008;57(2):260–269.
    1. Sato T, Iwaso H. An effectiveness study of hyaluronic acid (Hyabest J) in the treatment of osteoarthritis of the knee on the patint in the United States. Journal of New Remedies and Clinics. 2009;58(3):551–558.
    1. Iwaso H, Sato T. Examination of the efficacy and safety of oral administration of Hyabest J, highly pure hyaluronic acid, for knee joint pain. Journal of Japanese Society of Clinical Sports Medicine. 2009;17(3):566–572.
    1. Nagaoka I, Nabeshima K, Murakami S, et al. Evaluation of the effects of a supplementary diet containing chicken comb extract on symptoms and cartilage metabolism in patients with knee osteoarthritis. Experimental and Therapeutic Medicine. 2010;1(5):817–827.
    1. Kalman DS, Heimer M, Valdeon A, Schwartz H, Sheldon E. Effect of a natural extract of chicken combs with a high content of hyaluronic acid (Hyal-Joint) on pain relief and quality of life in subjects with knee osteoarthritis: a pilot randomized double-blind placebo-controlled trial. Nutrition Journal. 2008;7(1, article 3)
    1. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Annals of the Rheumatic Diseases. 1957;16(4):494–502.
    1. Doi T, Akai M, Fujino K, et al. Effect of home exercise of quadriceps on knee osteoarthritis compared with nonsteroidal antiinflammatory drugs: a randomized controlled trial. American Journal of Physical Medicine and Rehabilitation. 2008;87(4):258–269.
    1. Akai M, Doi T, Fujino K, Iwaya T, Kurosawa H, Nasu T. An outcome measure for Japanese people with knee osteoarthritis. Journal of Rheumatology. 2005;32(8):1524–1532.
    1. Balogh L, Polyak A, Mathe D, et al. Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs. Journal of Agricultural and Food Chemistry. 2008;56(22):10582–10593.
    1. Hara H, Haga S, Kasai T, Kiriyama S. Fermentation products of sugar-beet fiber by cecal bacteria lower plasma cholesterol concentration in rats. Journal of Nutrition. 1998;128(4):688–693.
    1. Kajimoto O, Odanaka Y, Sakamoto W, Yoshida K, Takahashi T. Clinical effects of dietary hyaluronic acid on dry skin. Journal of New Remedies and Clinics. 2001;50(4):548–560.
    1. Sato T, Sakamoto W, Odanaka W, Yoshida K, Urushibara O. Clinical effects of dietary hyaluronic acid on dry, rough skin. Aesthetic Dermatology. 2002;12:109–120.
    1. Asari A, Kanemitsu T, Kurihara H. Oral administration of high molecular weight hyaluronan (900 kDa) controls immune system via toll-like receptor 4 in the intestinal epithelium. Journal of Biological Chemistry. 2010;285(32):24751–24758.
    1. Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. Journal of Rheumatology. 1999;26(11):2423–2430.
    1. Noack W, Fischer M, Forster KK, Rovati LC, Setnikar I. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis and Cartilage. 1994;2(1):51–59.
    1. Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LC. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Archives of Internal Medicine. 2002;162(18):2113–2123.
    1. Anderson JW, Nicolosi RJ, Borzelleca JF. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy. Food and Chemical Toxicology. 2005;43(2):187–201.
    1. Hua J, Sakamoto K, Nagaoka I. Inhibitory actions of glucosamine, a therapeutic agent for osteoarthritis, on the functions of neutrophils. Journal of Leukocyte Biology. 2002;71(4):632–640.
    1. Fenton JI, Chlebek-Brown KA, Peters TL, Caron JP, Orth MW. Glucosamine HCl reduces equine articular cartilage degradation in explant culture. Osteoarthritis and Cartilage. 2000;8(4):258–265.
    1. Gouze JN, Bordji K, Gulberti S, et al. Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes. Arthritis and Rheumatism. 2001;44(2):351–360.
    1. Hua J, Suguro S, Hirano S, Sakamoto K, Nagaoka I. Preventive actions of a high dose of glucosamine on adjuvant arthritis in rats. Inflammation Research. 2005;54(3):127–132.
    1. Hua J, Sakamoto K, Kikukawa T, Abe C, Kurosawa H, Nagaoka I. Evaluation of the suppressive actions of glucosamine on the interleukin-1β-mediated activation of synoviocytes. Inflammation Research. 2007;56(10):432–438.
    1. Meikle PJ, Whittle AM, Hopwood JJ. Human acetyl-coenzyme A:α-glucosaminide N-acetyltransferase: kinetic characterization and mechanistic interpretation. Biochemical Journal. 1995;308(1):327–333.
    1. Punzi L, Schiavon F, Cavasin F, Ramonda R, Gambari PF, Todesco S. The influence of intra-articular hyaluronic acid on PGE2 and cAMP of synovial fluid. Clinical and Experimental Rheumatology. 1989;7(3):247–250.
    1. Sharif M, Kirwan JR, Elson CJ, Granell R, Clarke S. Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years. Arthritis and Rheumatism. 2004;50(8):2479–2488.
    1. Fukui N, Yamane S, Ishida S, et al. Relationship between radiographic changes and symptoms or physical examination findings in subjects with symptomatic medial knee osteoarthritis: a three-year prospective study. BMC Musculoskeletal Disorders. 2010;11, article 269
    1. Roos EM, Dahlberg L. Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: a four-month, randomized, controlled trial in patients at risk of osteoarthritis. Arthritis and Rheumatism. 2005;52(11):3507–3514.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅