StrongJoint™ Ultimate Joint Care is a revolutionary, fast-acting formula that has been scientifically formulated to help promote joint comfort and mobility. In addition to the popular ingredients in Joint Care Science such as Glucosamine, Chondroitin, MSM and Hyaluronic Acid, StrongJoint™ contains new breakthrough ingredients known as Collagen Type II and BosPure®.
Collagen Type II has been clinically proven to support healthy joint function and is found to be more effective than taking Glucosamine and Chondroitin alone. BosPure® is a patented Boswellia formula which helps in inflammatory issues and has been clinically shown to improve mobility in 7 days.
With increased mobility and joint comfort, StrongJoint™ can help you to pursue the activities you love and get back on track…fast!
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Collagen Type II
Collagen is a natural protein and the primary substance of the connective tissue that holds our body together. It is the main component of skin, cartilage, ligaments, and tendons. However after age of 25, our body’s natural production of collagen starts to reduce at the rate of 1.5% per year. Taking collagen supplements can help to replenish lost collagen, improve mobility, and support overall joint health.
Why Collagen Type II?
There are more than 25 types of collagen that naturally occur in the body. Scientific studies show that Collagen Type II is found to be the predominant type of collagen in the human articular cartilage. It makes up 50% of all the proteins in our cartilage and 85-90% of collagen in our articular cartilage.
Studies show that Collagen Type II has multiple protective benefits to our joint. It helps to:
BosPure® Boswellia (Boswellia Serrata, AKBA), is a clinically researched and uniquely standardized boswellia extract. Boswellia Serrata is one of nature’s oldest and most powerful bioactive compounds. It has been known to inhibit collagen degradation, reduce joint swelling, inflammation, and relieve pain due to stiffness in the joints.
MSM (methylsulfonylmethane) is a natural form of organic sulphur found throughout the body. It supports flexibility and strength in connective tissues and cell membranes. MSM has been widely used for the relief of inflammation, stiffness and swelling from arthritis. Studies show that MSM is effective to fight against Osteoarthritis and other joint conditions because of its high sulphur content.
Glucosamine sulphate is a compound found naturally in the cartilage matrix and synovial fluid. It acts like a lubricant, and keeps the joints moving smoothly. Taking glucosamine sulphate daily helps to repair damaged cartilage by replenishing the body’s supply of glucosamine.
Chondroitin sulphate provides the structural components of joint cartilage and facilitates the entry of glucosamine into joints. It helps to keep cartilage healthy by absorbing fluid into the connective tissue and promote elasticity in cartilage. Scientific studies also suggest that Chondroitin sulphate may be an effective treatment for osteoarthritis.
Hyaluronic acid is a gel-like substance found in every tissue of the body with the highest concentrations in connective tissue such as skin and cartilage. It works by acting like a lubricant and shock absorber in the joints and helps the joints to work properly.
Vitamin C is essential for formation of cartilage, collagen, and joint tissue. It is also a powerful antioxidant that can help protect the cartilages from harmful free radicals.
Vitamin D helps the body absorb calcium to keep bones strong and healthy.
Bio-2 is a piperine extract formula that can help increase the bioavailability and maximize absorption of Boswellia Serrata and other nutrients.
I am 49 years old. I used to have knee pain since many years ago and had difficulties in climbing the stairs and getting up after squatting down. But ever since I started taking StrongJoint for about 4 months, now I can feel the differences. I am able to climb the stairs without any problems or pain, and no problem in getting myself up after squatting down. I am happy with StrongJoint and am still taking it. Sometime, I’ve recommended to many people around me.
I used to encounter joint pain when I climb up the stairs. After trying US Clinicals StrongJoint, I feel that my joint problems have improved. Now I consume StrongJoint everyday, and I recommend to my brother too.
After trying StrongJoint for 2 weeks, I can really feel the effect, my knee is not as painful and there is lesser creaking sound. I am able to climb the stairs with lesser sufferings now. Those who are serious about protecting and strengthening their joints should try this product.
I saw the advertisement on Wanbao, a supplement that can be consumed for the prevention of cartilage loss, and decided to try as I have been experiencing creaking joints for 2 years. Currently I can feel mild joint pain, therefore I consumed StrongJoint for maintenance of joint health and prevention of loss of joint cartilage and creaking joints.
My knee always has a sharp pain as my work requires me to move about frequently. The doctor said I need to go for an operation but it doesn’t mean I would fully recover. Eventually my friend introduced me US Clinicals StrongJoint which lessen the pain I am experiencing. My trip to Japan this time round is no longer a burden. I am able to walk about freely from dawn to dusk all thanks to US Clinicals StrongJoint.
I love dancing and would always dance 3 times in a week. Due to this reason, my joint has been hurting for almost a year. In the past I have taken many other joint supplements but they don’t work for me. One day while I was browsing Lifestyle Magazine, I saw an advertisement on US Clinicals StrongJoint which captured my attention. After taking the capsule for 1 – 2 months, I could feel that my joints were not as pain as before. I have been taking this product for 6 months and will definitely recommend it to my friends.
I am a painter. As I have to stand, squat and climb the stairs to work every now and then, my shoulders and leg joints are always painful. Although I have tried various joint care supplements, they are not effective and now I am facing difficulties in my life due to this problem. Ever since my friend introduced Strong Joint to me, the pain on my joint doesn’t hurt as much. After 2 to 3 months, my knees no longer have creaking sound and my legs are more flexible when I am climbing up and down.
Take two capsules per day after meal.
You can start seeing results in joint comfort and mobility in a week. However, results may vary from every individual. You are suggested to take StrongJoint™ consecutively for at least 4-6 weeks to achieve best results.
No known side effect has been observed. All the ingredients in StrongJoint™ are tested and approved to ensure safety, purity and efficacy. It is therefore safe for long term consumption.
StrongJoint™ is a supplement formulated to supply important nutrients that are not always easy to obtain in sufficient amounts from diet. However, we recommend you to consult your health care practitioner concerning drug interactions if you are taking any medication.
- Activation of collagen type II expression in osteoarthritic and rheumatoid cartilage.
Thomas Aigner, et al, Virchows Archiv B Cell Pathol (1992) 62:337-345
Summary: In situ hybridization and immunohistochemical techniques were applied to investigate gene expression and extracellular deposition of collagen type II in normal, osteoarthritic and rheumatoid human articular cartilage. Normal cartilage showed an essentially even extracellular distribution of type II collagen with poly-and monoclonal antibodies, while only a few cells were positive for ~l(II) collagen mRNA. In situ hybridization of osteoarthritic and rheumatoid cartilage, however, showed strong enhancement of type II collagen gene expression; transcripts were observed predominantly in the upper middle zone of the articular cartilage while the upper layer was mostly negative and correlated with a zone of reduced proteoglycan staining. The elvated mRNA levels frequently coincided with pericellular immunostaining for type II collagen, indicative for enhanced synthesis of the protein. In two samples, however, pericellular loss of collagen type II staining was found despite positive cytoplasmic signals with the ~l(II) RNA probe, suggesting enhanced collagen destruction. Control hybridization with a probe for 18S rRNA revealed very few negative cells throughout both normal and arthritic cartilage samples, ruling out major cell necrosis in the specimens investigated. Thus, our observations identify sites of activated type II collagen synthesis in osteoarthritic cartilage that were predicted by previous biochemical studies and support the notion that damaged cartilage attempts to restore matrix by enhanced synthesis of its components.
- Can collagen type II sustain a methotrexate-induced therapeutic effect in patients with long-standing rheumatoid arthritis? A double-blind, randomized trial.
H J Hauselmann, M Caravatti, B Seifert, K Wang, P Bruckner, G Stucki, B A Michel, British journal of rheumatology 11/1998; 37(10):1110-7
Objective: Based on the results of two recently published, randomized, double-blind and placebo-controlled studies, a possible improvement in rheumatoid arthritis disease activity after oral tolerization with triple helical collagen type II has been suggested. The goal of this study was to go one step further and ask the question whether collagen type II can sustain the therapeutic effect induced by methotrexate, the most widely accepted disease-modifying anti-rheumatic drug in patients with long-standing rheumatoid arthritis.
Methods : Ninety-two patients with rheumatoid arthritis on stable therapy with methotrexate were enrolled in a 3 month double-blind, randomized and comparative study to examine the efficacy of oral triple helical collagen type II as compared to continuing methotrexate. The dose of methotrexate (or the respective placebo drug) and of concomitant corticosteroids was not changed and intra-articular corticosteroids were not allowed during the 3 months. The primary study endpoint was disease activity as measured by physician and patients.
Results: While patients under ongoing therapy with methotrexate had, as expected, no change in disease activity, almost all parameters of disease activity and outcome in patients under a daily oral dose of 0.5 mg triple helical collagen type II worsened significantly (highly significant difference in swollen joints, between the two groups, P < 0.0001). No significant differences in side-effects between the two groups during the study period could be demonstrated.
Conclusions: Substitution of methotrexate with daily 0.5 mg of triple helical collagen type II in patients with rheumatoid arthritis leads to a significant increase in disease activity, suggesting that oral collagen type II at the given dose is not capable of sustaining the methotrexate-induced anti-inflammatory effect in patients with long-standing rheumatoid arthritis.
- Oral administration of type-II collagen peptide 250-270 suppresses specific cellular and humoral immune response in collagen-induced arthritis
Ping Zhu, Xiao-Yan Li, Hong-Kun Wang, Jun-Feng Jia, Zhao-Hui Zheng, Jin Ding, Chun-Mei Fan, Clinical Immunology (2007) 122,75-84
Abstract: Oral antigen is an attractive approach for the treatment of autoimmune and inflammatory diseases. Establishment of immune markers and methods in evaluating the effects of antigen-specific cellular and humoral immune responses will help the application of oral tolerance in the treatment of human diseases. The present article observed the effects of chicken collagen II (CII), the recombinant polymerized human collagen II 250-270 (rhCII 250-270) peptide and synthesized human CII 250-270 (syCII 250-270) peptide on the induction of antigen-specific autoimmune response in rheumatoid arthritis (RA) peripheral blood mononuclear cells (PBMC) and on the specific cellular and humoral immune response in collagen-induced arthritis (CIA) and mice fed with CII (250-270) prior to immunization with CII. In the study, proliferation, activation and intracellular cytokine production of antigen-specific T lymphocytes were simultaneously analyzed by bromodeoxyuridine (BrdU) incorporation and flow cytometry at the single-cell level. The antigen-specific antibody and antibody-forming cells were detected by ELISA and ELISPOT, respectively. CII (250-270) was found to have stimulated the response of specific lymphocytes in PBMC from RA patients, including the increase expression of surface activation antigen marker CD69 and CD25, and DNA synthesis.
- Boswellic acids in chronic inflammatory diseases.
Ammon H P T, Planta medica 2006 Oct; 72(12):1100-16
Abstract: Oleogum resins from BOSWELLIA species are used in traditional medicine in India and African countries for the treatment of a variety of diseases. Animal experiments showed anti-inflammatory activity of the extract. The mechanism of this action is due to some boswellic acids. It is different from that of NSAID and is related to components of the immune system. The most evident action is the inhibition of 5-lipoxygenase. However, other factors such as cytokines (interleukins and TNF-alpha) and the complement system are also candidates. Moreover, leukocyte elastase and oxygen radicals are targets. Clinical studies, so far with pilot character, suggest efficacy in some autoimmune diseases including rheumatoid arthritis, Crohn’s disease, ulcerative colitis and bronchial asthma. Side effects are not severe when compared to modern drugs used for the treatment of these diseases.
- Boswellia serrata: An overall assessment of in Vitro, Preclinical, Pharmacokinetic and Clinical Data
Mona Abdel-Tawab, Oliver Werz and Manfred Schubert- Zsilavecz, Clin Pharmacokinet 2011;50 (6): 349 – 369
Abstract: Non-steroidal anti-inflammatory drug (NSAID) intake is associated with high prevalence of gastrointestinal or cardiovascular adverse effects. All efforts to develop NSAIDs that spare the gastrointestinal tract and the cardiovascular are still far from achieving a breakthrough. In the last two decades, preparations of the gum resin of Boswellia serrata (a traditional ayurvedic medicine) and of other Boswellia species have experienced increasing popularity in Western countries. Animal studies and pilot clinical trials support the potential of B. serrata gum resin extract (BSE) for the treatment of a variety of inflammatory diseases like inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and asthma. Moreover, in 2002 the European Medicines Agency classified BSE as an ‘orphan drug’ for the treatment of peritumoral brain oedema. Compared to NSAIDs, it is expected that the administration of BSE is associated with better tolerability, which needs to be confirmed in further clinical trials.
Until recently, the pharmacological effects of BSE were mainly attributed to suppression of leukotriene formation via inhibition of 5- lipoxygenase (5-LO) by two boswellic acids, 11-keto-s-boswellic acid (KBA) and acetyl-11-keto-s-boswellic acid (AKBA). These two boswellic acids have also been chosen in the monograph of Indian frankincense in European Pharmacopoeia 6.0 as markers to ensure the quality of the air-dried gum resin exudates of B. serrata. Furthermore, several dietary supplements advertise the enriched content of KBA and AKBA. However, boswellic acids failed to inhibit leukotriene formation in human whole blood, and pharmacokinetic data revealed very low concentrations of AKBA and KBA in plasma, being far below the effective concentrations for bioactivity in vitro. Moreover, permeability studies suggest poor absorption of AKBA following oral administration. In view of these results, the previously assumed mode of action – that is, 5-LO inhibition – is questionable. On the other hand, 100-fold higher plasma concentrations have been determined for s-boswellic acid, which inhibits microsomal prostaglandin E synthase-1 and the serine protease cathepsin G. Thus, these two enzymes might be reasonable molecular targets related to the anti-inflammatory properties of BSE. In view of the results of clinical trials and the experimental data from in vitro studies of BSE, and the avai lable pharmacokinetic and metabolic data on boswellic acids, this review presents different perspectives and gives a differentiated insight into the possible mechanisms of actions of BSE in humans. It underlines BSE as a promising alternative to NSAIDs, which warrants investigation in further pharmacological studies and clinical trials.
- A double blind, randomized, placebo controlled study of the efficacy and safety of 5-LoxinR for treatment of osteoarthritis of the knee
Krishanu Sengupta, et al, Arthritis research & therapy. 2008; 10 (4): R85
Introduction: 5-LoxinR is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-LoxinR in the treatment of osteoarthritis (OA) of the knee.
Methods: Seventy-five OA patients were included in the study. The patients received either 100 mg (n = 25) or 250 mg (n = 25) of 5-LoxinR daily or a placebo (n = 25) for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne’s Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. Additionally, the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement of a battery of biochemical parameters in serum and haematological parameters, and urine analysis were performed to evaluate the safety of 5-LoxinR in OA patients.
Results: Seventy patients completed the study. At the end of the study, both doses of 5-LoxinR conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients. Interestingly, significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-LoxinR as early as 7 days after the start of treatment. Corroborating the improvements in pain scores in treatment groups, we also noted significant reduction in synovial fluid matrix metalloproteinase-3. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups.
Conclusion: 5-LoxinR reduces pain and improves physical functioning significantly in OA patients; and it is safe for human consumption. 5-LoxinR may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients.
- Open, randomized, controlled clinical trial of Boswellia serrata extract as compared to valdecoxib in osteoarthritis of knee.
Sontakke S, Thawani V, Pimpalkhute S, Kabra P, Babhulkar S, Hingorani L, Indian Journal of Pharmacology. 2007; 39 (1) 27-29
Objective: To compare the efficacy, safety and tolerability of Boswellia serrata extract (BSE) in osteoarthritis (OA) knee with valdecoxib, a selective COX-2 inhibitor.
Materials and Methods: In a randomized, prospective, open-label, comparative study the efficacy, safety and tolerability of BSE was compared with valdecoxib in 66 patients of OA of knee for six months. The patients were assessed by WOMAC scale at baseline and thereafter at monthly interval till 1 month after drug discontinuation. Antero-posterior radiographs of affected knee joint were taken at baseline and after 6 months.
Results: In BSE group the pain, stiffness, difficulty in performing daily activities showed statistically significant improvement with two months of therapy which even lasted till one month after stopping the intervention. In valdecoxib group the statistically significant improvement in all parameters was reported after one month of therapy but the effect persisted only as long as drug therapy continued. Three patients from BSE group and two from valdecoxib group complained of acidity. One patient from BSE group complained of diarrhea and abdominal cramps.
Conclusion: BSE showed a slower onset of action but the effect persisted even after stopping therapy while the action of valdecoxib became evident faster but waned rapidly after stopping the treatment.
- Ist H15 (Harzextrakt von Boswellia serrata, “Weihrauch”) eine sinnvolle Erganzung zur etablierten medikamentosen Therapie der chronischen Polyarthritis?–Ergebnisse einer doppelblinden Pilotstudie.
[Is H15 (resin extract of Boswellia serrata, “incense”) an efficient supplementation to established drug therapy in RA? – Results of a double blinded pilot trial]
Sander O, Herborn G, Rau R. Z Rheumatol. 1998 Feb; 57(1): 11-6.
Background: Leukotrienes and prostaglandines are important mediators of inflammation. While prostaglandine synthesis can be influenced by NSAIDs therapeutical approaches to the 5-lipoxygenase pathway are rare. Resinous extracts of Boswellia serrata (H15, indish incense), known from traditional ayurvedic medicine, decrease leukotriene synthesis in vitro. Case reports suggest a clinical role for that drug.
Methods: Outpatients with active RA have been enrolled into a multicenter controlled trial. Patients received 9 tablets of active drug (3600 mg) or placebo daily in addition to their previous therapy. Doses of NSAIDs could be adjusted on demand. Efficacy parameters, Ritchies Index for swelling and pain, ESR, CRP, pain on VAS and NSAID dose were documented at baseline and 6 and 12 weeks after initiation. Mean values and medians were calculated to compare the groups for significant or clinically relevant change from baseline or difference between both groups at any time point of observation.
Results: A total of 78 patients were recruited in 4 centers, the data have been published in abstract form. Only 37 patients (verum 18, placebo 19), enrolled in Ratingen were available for detailed efficacy and safety analysis. All evaluations in these patients were performed by one investigator (G.H.). There was no subjective, clinical or laboratory parameter showing a significant or clinically relevant change from baseline or difference between both groups at any time point of observation. The mean NSAID dose reduction reached levels of 5.8% (H15) and 3.1% (placebo). One patient in each group showed a good response in all parameters but 4 patients in each group worsened. The others showed no alteration of their disease. CONCLUSION: Treatment with H15 showed no measurable efficacy. Controlled studies including a greater patient population are necessary to confirm or reject our results.
- Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee –A randomized double blind placebo controlled trial
N. Kimmatkar, V. Thawani, L. Hingorani, and R. Khiyani; Phytomedicine 10: 3–7 (2003)
Summary: Osteoarthritis is a common, chronic, progressive, skeletal, degenerative disorder, which commonly affects the knee joint. Boswellia serrata tree is commonly found in India. The therapeutic value of its gum (guggulu) has been known. It posses good anti-inflammatory, anti-arthritic and analgesic activity. A randomized double blind placebo controlled crossover study was conducted to assess the efficacy, safety and tolerability of Boswellia serrata Extract (BSE) in 30 patients of osteoarthritis of knee, 15 each receiving active drug or placebo for eight weeks. After the first intervention, washout was given and then the groups were crossed over to receive the opposite intervention for eight weeks. All patients receiving drug treatment reported decrease in knee pain, increased knee flexion and increased walking distance. The frequency of swelling in the knee joint was decreased. Radiologically there was no change. The observed differences between drug treated and placebo being statistically significant, are clinically relevant. BSE was well tolerated by the subjects except for minor gastrointestinal ADRs. BSE is recommended in the patients of osteoarthritis of the knee with possible therapeutic use in other arthritis.
- Special extract of BOSWELLIA serrata (H 15) in the treatment of rheumatoid arthritis
Etzel R. Phytomedicine. 1996 May;3(1):91-4.
Summary: H15, a special extract of the gum resin of Boswellia serrata (BS) is effective in the treatment of rheumatoid arthritis (RA). These findings were obtained in more than 260 patients by using a range of different clinical approaches for evaluation. The criteria for assessment were mainly joint swelling, pain, erytrocyte sedimentation rate (ESR), stiffness, additional use of NSAID, side effects and tolerance. The therapeutic action was mainly proven by comparing H15 with a placebo standard therapy. H15 is:
- normally not used for acute pain therapy;
- a disease-modifying agent and can replace other disease-modifying therapies;
- beneficial in early use;
- also beneficial when used with current disease-modifying drugs;
- well tolerated and safe in early use and long-term therapy.
- Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis
David E. Trentham, et al, Science, New Series, Vol. 261, No. 5129 (Sep. 24, 1993), pp. 1727-1730
Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type 11 collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type 11 collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.
- Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial
David C. Crowley, et al, Int J Med Sci 2009; 6(6):312-321.
Abstract : Previous studies have shown that undenatured type II collagen (UC-II) is effective in the treatment of rheumatoid arthritis, and preliminary human and animal trials have shown it to be effective in treating osteoarthritis (OA). The present clinical trial evaluated the safety and efficacy of UC-II as compared to a combination of glucosamine and chondroitin (G+C) in the treatment of OA of the knee. The results indicate that UC-II treatment was more efficacious resulting in a significant reduction in all assessments from the baseline at 90 days; whereas, this effect was not observed in G+C treatment group. Specifically, although both treatments reduced the Western Ontario McMaster Osteoarthritis Index (WOMAC) score, treatment with UC-II reduced the WOMAC score by 33% as compared to 14% in G+C treated group after 90 days. Similar results were obtained for visual analog scale (VAS) scores. Although both the treatments reduced the VAS score, UC-II treatment decreased VAS score by 40% after 90 days as compared to 15.4% in G+C treated group. The Lequesne’s functional index was used to determine the effect of different treatments on pain during daily activities. Treatment with UC-II reduced Lequesne’s functional index score by 20% as compared to 6% in G+C treated group at the end of 90-day treatment. Thus, UC-II treated subjects showed significant enhancement in daily activities suggesting an improvement in their quality of life.
- Effect of Intra-articular Injection of Hyaluronic Acid in Rheumatoid Arthritis Patients with Knee Osteoarthritis
Chen-Liang Chou, et al, J Chin Med Assoc2008; 71(8):411–415
Background: Intra-articular injection of hyaluronic acid (HA) is a well-documented treatment for knee osteoarthritis (OA). One of the multifactorial mechanisms is that exogenous HA can stimulate endogenous HA production. HA can regulate the growth and function of chondrocytes by binding to CD44 receptors on the chondrocytes. Synovitis is often found in patients with rheumatoid arthritis (RA) and is supposed to result from CD44 activity. The aim of this study was to investigate the effect of intra-articular injection of HA in patients with RA combined with knee OA.
Methods: Twenty RA patients with OA knees were enrolled; 11 patients were placed into a stage II group and 9 into a stage III group, in accordance with the Kellgren-Lawrence classification of knee OA. All patients received intra-articular injection of HA (ARTZ) once a week for 5 weeks, and were evaluated with the WOMAC index (including the pain, stiffness and physical function subscales) at baseline, week 5 and week 9. The Friedman test and Wilcoxon signed rank test with Bonferroni correction method were used for statistical analysis.
Results: The effect of intra-articular injection of HA was significant at week 5 (p < 0.0167) and persisted to week 9 (p < 0.0167). This therapy was equally efficacious with stage II and stage III patients, with no difference between the 2 groups.
Conclusion: Intra-articular injection of HA was beneficial in patients with RA combined with knee OA.
- Efficacy of intra-articular hyaluronic acid in patients with osteoarthritis of the ankle: a prospective study
Dr Shu-Fen Sun M.D., et al, OsteoArthritis and Cartilage (2006) 14, 867 874
Objective: To investigate the efficacy, safety and the duration of treatment effectiveness of intra-articular hyaluronic acid (Artz, Japan) in patients with ankle osteoarthritis (OA).
Method: As a prospective clinical trial, 93 patients with unilateral ankle pain for at least 6 months and radiographically classified as Kellgren-Lawrence grade I or II ankle OA were included. After five weekly intra-articular Artz injections, the Ankle Osteoarthritis Scale (AOS), the American Orthopaedic Foot and Ankle Society (AOFAS) ankle/hindfoot score, ankle sagittal range of motion (ROM), patients’ global satisfaction, local adverse events and consumption of rescue analgesics were analyzed.
Results: Seventy-five patients completed the study. Significant improvement in AOS and AOFAS ankle/hindfoot scores was noted at 1 week, 1 month, 3 months and 6 months post the fifth injection (P < 0.001 compared with baseline). The mean reduction of AOS score was 1.9, 2.6, 2.5 and 2.6 at each following visit (P < 0.001). The mean AOFAS ankle/hindfoot score improved from 64 points at baseline to 75, 78, 78, and 78 points at 1 week, 1 month, 3 months and 6 months, respectively, post the fifth injection (P < 0.001). Ankle sagittal ROM did not improve significantly (P > 0.05). The majority of patients reported satisfaction at 1 week (100%), 1 month (100%), 3 months (90.7%) and 6 months (86.7%) follow-up. Local adverse events occurred in 6.7% of patients. Acetaminophen consumption dropped significantly following treatment (P < 0.001).
Conclusion: Five weekly intra-articular injections of Artz provide pain relief and functional improvements in patients with Kellgren-Lawrence grades I and II ankle OA. The clinical effect was rapid at 1 week and may last for 6 months or more.
- Effectiveness of intra-articular hyaluronic acid for ankle osteoarthritis treatment: a systematic review and meta-analysis.
Chang KV, et al, Arch Phys Med Rehabil. 2013 May;94(5):951-60.
Objectives: To explore the effectiveness and safety of hyaluronic acid (HA) administration for ankle osteoarthritis (OA), and to investigate the effects of variations in HA regimens on treatment responses.
Data sources: Electronic databases, including PubMed and Scopus, were searched from January 1995 to June 2012.
Study selection: We included randomized controlled trials (RCTs) or prospective cohort studies that employed intra-articular HA to treat ankle OA. Four RCTs, 1 comparative study, and 4 single-arm prospective studies were identified, comprising 354 participants.
Data extraction: We determined effect sizes for selected studies by extracting pain scores from ankle OA or visual analog scales before and after HA or reference treatments. Meta-regression was implemented to determine whether outcomes were modified by variations in HA regimens.
Data synthesis: The pooled effect size of improvement scores from baseline was 2.01 (95% confidence interval [CI], 1.27-2.75), whereas the values of comparisons with reference treatments including saline, exercise, and arthroscopy reduced to 0.85 (95% CI, -0.13 to 1.83). The placebo effect of the injection procedure accounted for 87% of the observed efficacy of HA treatment. The meta-regression indicated that the molecular weight was not associated with the magnitude of pain relief, but increases in total doses and active ingredients administered might result in a better outcome. Conversely, increases in injection volumes might cause a reduction of effect sizes. Regarding the side effects, the use of extremely high molecular weight HA frequently caused early postinjection pain.
Conclusions: Intra-articular HA administration can significantly reduce pain in ankle OA compared with the condition before treatment, and it is likely superior to reference therapy. We recommend using multiple doses with an appropriate injection volume to achieve maximum effectiveness.
- Intra-articular Hyaluronic Acid Potential Treatment of Younger Patients with Knee Injury andor Post-Traumatic Arthritis
Jazrawi LM, Rosen J. The Physician and Sportsmedicine, 2011 May; 39(2):107-13.
Abstract: Anterior cruciate ligament (ACL) and meniscal injuries are common in both athletes and the general population. Such injuries may lead to early-onset post-traumatic osteoarthritis (OA) in 50% to 60% of patients, regardless of whether patients had reconstruction performed. In younger patients, intra-articular (IA) injection of hyaluronic acid (HA) may be useful for improving short-term outcomes and possibly slowing or arresting the progression of OA. Hyaluronic acid has anti-inflammatory, anabolic, and chondroprotective effects, which have been demonstrated in in vitro and animal models of meniscal and ACL injury. Results from several clinical trials and patient series have demonstrated the benefit of IA HA injection in younger patients with acute knee damage, including symptomatic meniscal tears and isolated ACL injury with chondral injury, although evidence for this is less extensive than the large database supporting the use of IA HA injection in older patients with knee OA. Administration of HA has been shown to improve outcomes in patients undergoing knee arthroscopy, and IA HA also has direct antinociceptive effects that may contribute to its benefit in patients with patellofemoral pain. However, the use of IA HA in patients with ACL injury or early OA has been evaluated in only a few studies. Thus, there is a need for larger-scale randomized controlled trials with longer durations of follow-up to provide more definitive evaluation of the efficacy and safety of IA HA in these patients. Such studies provide an opportunity to further elucidate the benefits of IA HA in younger patients with knee damage and may result in appropriate expansion of use in this large population, which has a substantial need for new treatment alternatives.
- Relationship between serum hyaluronic acid level and disease activity in early rheumatoid arthritis
M Majeed, F McQueen, S Yeoman, L McLean, Ann Rheum Dis 2004; 63:1166–1168.
Objectives: To measure hyaluronic acid (HA) levels, which are raised in active rheumatoid arthritis (RA), in patients with early RA, and to assess the correlation with clinical and laboratory indices of disease activity and with subsequent radiographic erosive status.
Patients and methods: Patients fulfilling ACR criteria were recruited into a prospective cohort within 6 months of disease onset and reviewed every 6 months. An HA binding protein based sandwich ELISA was used to measure HA in 240 sera from 82 patients at regular intervals.
Results: Patients had higher HA levels than age matched healthy blood donor controls (median 37.4 v 29.1 ng/ml, respectively, p,0.02), which increased with more prolonged disease. Baseline HA level correlated with measures of disease activity, including swollen and tender joint counts, HAQ, global assessments, ESR, and CRP; was higher in men; and increased with age. There was no relationship with HLA-DRB1 shared epitope or rheumatoid factor status. At 6 and 12 month follow up visits, HA levels were higher in patients who later developed erosions. However, a raised HA level was not a good predictor of erosions.
Conclusions: Serum HA level correlates with clinical and laboratory measures of disease activity in early RA, but is unlikely to be of practical use in clinical practice.
- Reduced pain from osteoarthritis in hip joint or knee joint during treatment with calcium ascorbate. A randomized, placebo-controlled cross-over trial in general practice
Hertz Jensen N. Ugeskr Laeger 2003;165:2563–6
Introduction: Although vitamin C is essential for the formation of collagen and proteoglycan and has been shown to minimise surgically induced arthritis in guinea pigs, no controlled trial has examined its effect on human osteoarthritis.
Material and methods: The trial was a multicenter, double-blind, randomised, placebo-controlled, crossover-trial performed by ten general practitioners. The Declaration of Helsinki and the European guidelines for good clinical practice were strictly followed. One hundred and thirty-three patients with radiographically verified symptomatic osteoarthritis of the hip joints and/or the knee joints were treated with one gram of calcium ascorbate or identically looking placebo tablets. The calcium ascorbatetablets and the placebo tablets should be swallowed daily for 14 +/- 3 days respectively, separated by 7 +/- 3 days wash out. The main outcome measure was difference on the 100 mm visual analog scale (VAS) score for pain in a preselected joint. The secondary outcomes were Lequesne score for function and patient preference.
Results: Calculated on an intention-to-treat principle, calcium ascorbate reduced pain significantly compared to placebo (p = 0.0078 by analysis of variance between groups (ANOVA) for difference in VAS, mean difference 4.6 mm (95% CI 1.2-8.0). Similar superiority was found for Lequesne index (p = 0.036, difference 0.56 (95% CI 0.04-1.08) and for patient preference (p = 0.012).
Discussion: The demonstrated effect is less than half as pronounced as commonly reported forNSAID etc. If the finding can be reproduced with a smaller, acceptable intake of vitamin C this would be of importance considering the large prevalence of osteoarthrosis.
- Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis
Pavelka K, et al, Arch Intern Med. 2002 Oct 14;162(18):2113-23.
Background: Conventional symptomatic treatments for osteoarthritis do not favorably affect disease progression. The aim of this randomized, placebo-controlled trial was to determine whether long-term (3-year) treatment with glucosamine sulfate can modify the progression of joint structure and symptom changes in knee osteoarthritis, as previously suggested.
Methods: Two hundred two patients with knee osteoarthritis (using American College of Rheumatology criteria) were randomized to receive oral glucosamine sulfate, 1500 mg once a day, or placebo. Changes in radiographic minimum joint space width were measured in the medial compartment of the tibiofemoral joint, and symptoms were assessed using the algo-functional indexes of Lequesne and WOMAC (Western Ontario and McMaster Universities).
Results: Osteoarthritis was of mild to moderate severity at enrollment, with average joint space widths of slightly less than 4 mm and a Lequesne index score of less than 9 points. Progressive joint space narrowing with placebo use was -0.19 mm (95% confidence interval, -0.29 to -0.09 mm) after 3 years. Conversely, there was no average change with glucosamine sulfate use (0.04 mm; 95% confidence interval, -0.06 to 0.14 mm), with a significant difference between groups (P =.001). Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings (>0.5 mm): 5% vs 14% (P =.05). Symptoms improved modestly with placebo use but as much as 20% to 25% with glucosamine sulfate use, with significant final differences on the Lequesne index and the WOMAC total index and pain, function, and stiffness subscales. Safety was good and without differences between groups.
Conclusion: Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification.
- Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis evidence from two 3-year studies
Bruyere O, et al, Menopause: The Journal of The North American Menopause Society Vol. 11, No. 2, pp. 138–143
Objective: To investigate the effect of glucosamine sulfate on long-termsymptoms and structure progression in postmenopausal women with knee osteoarthritis (OA).
Design: This study consisted of a preplanned combination of two three-year, randomized, placebo-controlled, prospective, independent studies evaluating the effect of glucosamine sulfate on symptoms and structure modification in OA and post-hoc analysis of the results obtained in postmenopausal women with knee OA. Minimal joint space width was assessed at baseline and after 3 years from standing anteroposterior knee radiographs. Symptoms were scored by the algofunctional WOMAC index at baseline and after 3 years. All primary statistical analyses were performed in intention-to-treat, comparing joint space width and WOMAC changes between groups by ANOVA.
Results: Of 414 participants randomized in the two studies, 319 were postmenopausal women. At baseline, glucosamine sulfate and placebo groups were comparable for demographic and disease characteristics, both in the general population and in the postmenopausal women subset. After 3 years, postmenopausal participants in the glucosamine sulfate group showed no joint space narrowing [joint space change of +0.003 mm (95% CI, -0.09 to 0.11)], whereas participants in the placebo group experienced a narrowing of -0.33mm(95%CI, -0.44 to -0.22; P < 0.0001 between the two groups). Percent changes after 3 years in the WOMAC index showed an improvement in the glucosamine sulfate group [-14.1% (95%, -22.2 to -5.9)] and a trend for worsening in the placebo group (5.4% (95% CI, -4.9 to 15.7) (P = 0.003 between the two groups).
Conclusion: This analysis, focusing on a large cohort of postmenopausal women, demonstrated for the first time that a pharmacological intervention for OA has a disease-modifying effect in this particular population, the most frequently affected by knee OA.
- Evaluation of the lipoxygenase inhibitory effect of boswellic acid analogues
Dr.P.R Sudhakaran, Manju devi.S
Aim: To compare the ability of different water soluble preparations of Boswellic acid with varying content of AKBA to inhibit lipoxygenases.
Materials: All chemicals used were of high purity analytical grade reagents. Histopaque 1077, RPMI-1640, penicillin, streptomycin, tris, bovine serum albumin and linoleic acid were obtained from Sigma Chemicals Co, USA.
Methods: 1. Isolation of monocytes from human blood. Peripheral blood mononuclear cells were isolated from anticoagulated blood of healthy donors using Histopaque 1077 as per manufacturer’s instruction. Briefly anticoagulated blood was layered over equal volume of Histopaque1077. After centrifugation at 400g for 30 minutes at room temperature, mononuclear cells were collected from interface and resuspended in 2ml PBS and mixed by gentle aspiration. Cells were sedimented by centrifugation at 250g for 10 minutes, washed and resuspended in 0.5ml PBS-Tween and was lysed by three freeze thaw cycles. From inflammatory humans also peripheral blood monocytes were isolated and used for assay. 2. Culture of Peripheral Blood Mononuclear Cells. The peripheral blood mononuclear cells isolated from anticoagulated blood were cultured in 35mm culture plates in RPMI medium supplemented with 5% homologous serum and were maintained by incubating the plates in a carbon dioxide incubator at 370C in 95% air and 5% carbon dioxide atmosphere. The cells were activated using 40μg of Concanavalin A and the effects of different analogues of Boswellic acid on LOX activity were studied. 3. Assay of LOX activity. 4. Protein estimation. Protein was estimated by the method of Lowry et al.
Results and discussion: To study the inhibitory effect of different preparations of Boswellic acid containing varying proportion of BA and AKBA on lipoxygenases, human monocytes were used as sources. 5-LOX and 15-LOX activity were analysed in both normal and inflammatory condition and the results are given below.