Wetenschappelijk onderzoek over artrose

Het protocol voor de behandeling artrose (gewrichtsslijtage) is op basis van wetenschappelijke publicaties ontwikkeld. Hierbij is gebruik gemaakt van hoog gekwalificerd recent onderzoek dat wordt gepubliceerd in de PubMed database. Placebo controlled onderzoek, meta analyses en reviews hebben de voorkeur. Dit soort onderzoek valt onder Evidence Based Medicine.

OA = Osteoarthritis = Artrose

Pathologie artrose

Algemeen

REVIEW

1. Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF. Ann Intern Med. 2000 Oct 17;133(8):635-46. Osteoarthritis: new insights. Part 1: the disease and its risk factors
   Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weight-bearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability.[Article]
   
2. Felson DT, Lawrence RC, Hochberg MC, McAlindon T, Dieppe PA, Minor MA, Blair SN, Berman BM, Fries JF, Weinberger M, Lorig KR, Jacobs JJ, Goldberg V. Ann Intern Med. 2000 Nov 7;133(9):726-37.
   Part 2 focuses on treatment approaches; evidence for the efficacy of commonly used oral therapies is reviewed and information on alternative therapies, including nutriceuticals and acupuncture, is presented. Biomechanical interventions, such as exercise and bracing, and behavioral interventions directed toward enhancing self-management are reviewed. Current surgical approaches are described and probable future biotechnology-oriented approaches to treatment are suggested.[Article]
   

Collageen degradatie

REVIEW

3. Kurz B, Lemke AK, Fay J, Pufe T, Grodzinsky AJ, Schünke M. Ann Anat. 2005 Nov;187(5-6):473-85. Pathomechanisms of cartilage destruction by mechanical injury
   Mechanical injury is considered to be a major inductor of articular cartilage destruction and therefore a risk factor for the development of secondary osteoarthritis. Mechanical injury induces damage to the tissue matrix directly or mediated by chondrocytes via expression of matrix-degrading enzymes and reduction of biosynthetic activity. As a consequence the mechanical properties of cartilage change.[Abstract]
   
4. Lane Smith R, Trindade MC, Ikenoue T, Mohtai M, Das P, Carter DR, Goodman SB, Schurman DJ. Biorheology. 2000;37(1-2):95-107. Effects of shear stress on articular chondrocyte metabolism
   The articular cartilage of diarthrodial joints experiences a variety of stresses, strains and pressures that result from normal activities of daily living. In normal cartilage, the extracellular matrix exists as a highly organized composite of specialized macromolecules that distributes loads at the bony ends. The chondrocyte response to mechanical loading is recognized as an integral component in the maintenance of articular cartilage matrix homeostasis. With inappropriate mechanical loading of the joint, as occurs with traumatic injury, ligament instability, bony malalignment or excessive weight bearing, the cartilage exhibits manifestations characteristic of osteoarthritis. Breakdown of cartilage in osteoarthritis involves degradation of the extracellular matrix macromolecules and decreased expression of chondrocyte proteins necessary for normal joint function.[Abstract]
   

STUDY

5. Tchetina EV, Squires G, Poole AR. J Rheumatol. 2005 May;32(5):876-86. Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions
   Very early focal degeneration in knee articular cartilage is accompanied by upregulation of collagenase activity and expression of genes associated with chondrocyte terminal differentiation and matrix degradation. Thus chondrocyte differentiation may be closely related to the very early development of cartilage degeneration such as occurs in OA.[Abstract]
   
6. Squires GR, Okouneff S, Ionescu M, Poole AR. Arthritis Rheum. 2003 May;48(5):1261-70. The pathobiology of focal lesion development in aging human articular cartilage and molecular matrix changes characteristic of osteoarthritis
   These results demonstrate that lesions seen in aging exhibit molecular changes in matrix turnover similar to those seen in OA articular cartilage at arthroplasty, but not in healthy normal aging cartilage. The direct relationships between type II collagen cleavage and denaturation and the inverse relationship between type II collagen content and cleavage or denaturation implicate collagenase activity and damage to collagen in this loss of collagen during lesion developmen.[Article]
   

Oxidatieve stress

REVIEW

7. Henrotin YE, Bruckner P, Pujol JP Osteoarthritis Cartilage. 2003 Oct;11(10):747-55. The role of reactive oxygen species in homeostasis and degradation of cartilage
   This review of the literature supports the concept that ROS are not only deleterious agents involved in cartilage degradation, but that they also act as integral factors of intracellular signaling mechanisms.[Abstract]
   
8. Bonet ML, Granados N, Palou A. Curr Drug Targets. 2011 Dec;12(14):2103-28. Molecular players at the intersection of obesity and osteoarthriti
   Dysregulated production of adipose tissue-derived inflammatory mediators, hyperlipidemia, and increased systemic oxidative stress are conditions frequently associated with obesity that may favor joint degeneration.[Abstract]
   

STUDY

9. Yudoh K, Nguyen vT, Nakamura H, Hongo-Masuko K, Kato T, Nishioka K. Arthritis Res Ther. 2005;7(2):R380-91. Epub 2005 Jan 26. Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis: oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function
   Oxidative stress leads to increased risk for osteoarthritis (OA) but the precise mechanism remains unclear.[Article]
   

Metabool syndroom

REVIEW

10. Zhuo Q, Yang W, Chen J, Wang Y. Nat Rev Rheumatol. 2012 Dec;8(12):729-37. doi: 10.1038/nrrheum.2012.135. Metabolic syndrome meets osteoarthriti
    In this Review, we summarize the shared mechanisms of inflammation, oxidative stress, common metabolites and endothelial dysfunction that characterize the aetiologies of OA and MetS, and nominate metabolic OA as the fifth component of MetS. We also describe therapeutic opportunities that might arise from uniting these concepts.[Abstract]
    

Pycnogenol

11. Cisár P1, Jány R, Waczulíková I, Sumegová K, Muchová J, Vojtassák J, Dura?ková Z, Lisý M, Rohdewald P. Phytother Res. 2008 Aug;22(8):1087-92. doi: 10.1002/ptr.2461. Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis
    Results show that Pycnogenol in patients with mild to moderate OA improves symptoms and is able to spare NSAIDs.[Abstract]
    
12. Medical management of osteoarthritis of the knee and hip joints
    
    Osteoarthritis (OA) is a chronic, degenerative disorder of multifactorial aetiology, characterised by loss of articular cartilage and periarticular bone remodelling. OA causes joint pain, typically worse with weight bearing and activity, and stiffness after inactivity. There is no cure, and gradual, although slow, progression is most common. Almost 1.2 million Australians have symptoms of OA, and 13% are classified as disabled or handicapped. As well as affecting over half of people aged over 75 years, OA is a significant problem for 10% of adults still in the workforce. Overall, OA is the leading cause of musculoskeletal pain, disability and handicap in Australia.

    Goals of managing OA include controlling pain, maintaining and improving the range of movement and stability of affected joints, and limiting functional impairment. These goals should be achieved with minimal toxicity. Joint arthroplasty is indicated by end-stage joint failure with intractable pain, but most patients will be managed without surgery. Management must be individualised and patient-centred, and usually involves multiple strategies. Most morbidity is associated with OA of the large weight-bearing joints (the knee and hip). Here, we provide a pragmatic outline of the medical management of OA of these joints.

13. The pathophysiology of osteoarthritis
    
    Osteoarthritis (OA) is a complex disease whose pathogenesis includes the contribution of biomechanical and metabolic factors which, altering the tissue homeostasis of articular cartilage and subchondral bone, determine the predominance of destructive over productive processes. A key role in the pathophysiology of articular cartilage is played by cell/extra-cellular matrix (ECM) interactions, which are mediated by cell surface integrins. In a physiologic setting, integrins modulate cell/ECM signaling, essential for regulating growth and differentiation and maintaining cartilage homeostasis. During OA, abnormal integrin expression alters cell/ECM signaling and modifies chondrocyte synthesis, with the following imbalance of destructive cytokines over regulatory factors. IL-1, TNF-alpha and other pro-catabolic cytokines activate the enzymatic degradation of cartilage matrix and are not counterbalanced by adequate synthesis of inhibitors. The main enzymes involved in ECM breakdown are metalloproteinases (MMPs), which are sequentially activated by an amplifying cascade. MMP activity is partially inhibited by the tissue inhibitors of MMPs (TIMPs), whose synthesis is low compared with MMP production in OA cartilage. Intriguing is the role of growth factors such as TGF-beta, IFG, BMP, NGF, and others, which do not simply repair the tissue damage induced by catabolic factors, but play an important role in OA pathogenesis.
14. The role Protein kinase Czeta is up-regulated in osteoarthritic cartilage and is required for activation of NF-kappaB by tumor necrosis factor and interleukin-1 in articular chondrocytes
    
    Protein kinase Czeta (PKCzeta) is an intracellular serine/threonine protein kinase that has been implicated in the signaling pathways for certain inflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha), in some cell types. A study of gene expression in articular chondrocytes from osteoarthritis (OA) patients revealed that PKCzeta is transcriptionally up-regulated in human OA articular cartilage clinical samples. This finding led to the hypothesis that PKCzeta may be an important signaling component of cytokine-mediated cartilage matrix destruction in articular chondrocytes, believed to be an underlying factor in the pathophysiology of OA. IL-1 treatment of chondrocytes in culture resulted in rapidly increased phosphorylation of PKCzeta, implicating PKCzeta activation in the signaling pathway. Chondrocyte cell-based assays were used to evaluate the contribution of PKCzeta activity in NF-kappaB activation and extracellular matrix degradation mediated by IL-1, TNF, or sphingomyelinase. In primary chondrocytes, IL-1 and TNF-alpha caused an increase in NF-kappaB activity resulting in induction of aggrecanase-1 and aggrecanase-2 expression, with consequent increased proteoglycan degradation. This effect was blocked by the pan-specific PKC inhibitors RO 31-8220 and bisindolylmaleimide I, partially blocked by Gö 6976, and was unaffected by the PKCzeta-sparing inhibitor calphostin C. A cell-permeable PKCzeta pseudosubstrate peptide inhibitor was capable of blocking TNFand IL-1-mediated NF-kappaB activation and proteoglycan degradation in chondrocyte pellet cultures. In addition, overexpression of a dominant negative PKCzeta protein effectively prevented cytokine-mediated NF-kappaB activation in primary chondrocytes. These data implicate PKCzeta as a necessary component of the IL-1 and TNF signaling pathways in chondrocytes that result in catabolic destruction of extracellular matrix proteins in osteoarthritic cartilage.
15. Protein kinase Czeta is up-regulated in osteoarthritic cartilage and is required for activation of NF-kappaB by tumor necrosis factor and interleukin-1 in articular chondrocytes
    
    In summary, modulation of cytokines that control MMP gene up-regulation would appear to be fertile targets for drug development in the treatment of OA. Several studies illustrate the potential importance of modulating IL-1 activity as a means to reduce the progression of the structural changes in OA. In the experimental dog and rabbit models of OA, we have demonstrated that in vivo intraarticular injections of the IL-Ra gene can prevent the progression of structural changes in OA. Future directions in the research and treatment of osteoarthritis (OA) will be based on the emerging picture of pathophysiological events that modulate the initiation and progression of OA.
16. The contribution of adipose tissue and adipokines to inflammation in joint disease
    
    Adipokines are proteins produced by white adipose tissue, which is an active secretory organ. Regulation of immune and inflammatory responses is among the multiple physiological processes involving adipokines. Leptin, adiponectin and resistin are the most extensively studied adipokines. Leptin may promote inflammation by inducing Th1 phenotype development, whereas adiponectin may combat inflammation by reducing the production of pro-inflammatory cytokines. Resistin belongs to a family of proteins found in foci of inflammation, where they contribute to the inflammatory response. All three adipokines have been detected in synovial fluid from joints affected with the inflammatory disease rheumatoid arthritis (RA) or the degenerative disease osteoarthritis (OA). Recent evidence points to involvement of leptin in RA and OA and indicates that adiponectin and/or resistin mediate inflammation in arthritis. Thus, fat tissue is an active organ whose products contribute to inflammatory and degenerative processes underlying common joint diseases.
17. Adipose tissue, adipokines, and inflammation
    
    White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-alpha, IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified.

Inflammation

META

1. Jin X1, Beguerie JR2, Zhang W3, Blizzard L1, Otahal P1, Jones G1, Ding C4. Ann Rheum Dis. 2015 Apr;74(4):703-10. doi: 10.1136/annrheumdis-2013-204494. Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis
   Low-grade systemic inflammation may play a greater role in symptoms rather than radiographic changes in OA.[Abstract]
   

REVIEW

2. Chin KY1. Drug Des Devel Ther. 2016 Sep 20;10:3029-3042. eCollection 2016. The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis
   Osteoarthritis is a degenerative disease of the joint affecting aging populations worldwide. It has an underlying inflammatory cause, which contributes to the loss of chondrocytes, leading to diminished cartilage layer at the affected joints.[Article]
   

REVIEW

3. Robinson WH1,2, Lepus CM1,2, Wang Q1,2, Raghu H1,2, Mao R1,2, Lindstrom TM1,2, Sokolove J1,2 Nat Rev Rheumatol. 2016 Oct;12(10):580-92. doi: 10.1038/nrrheum.2016.136. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis
   Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis, increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies. [Abstract]
   

Groenlipmossel

CLINICAL

1. Coulson S1, Butt H, Vecchio P, Gramotnev H, Vitetta Inflammopharmacology. 2013 Feb;21(1):79-90. doi: 10.1007/s10787-012-0146-4 Green-lipped mussel extract (Perna canaliculus) and glucosamine sulphate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profile
   Both GLM and GS reduced OA symptoms.[Abstract]
   

REVIEW

2. Brien S1, Prescott P, Coghlan B, Bashir N, Lewith G. QJM. 2008 Mar;101(3):167-79. doi: 10.1093/qjmed/hcm108. Systematic review of the nutritional supplement Perna Canaliculus (green-lipped mussel) in the treatment of osteoarthritis
   The data from the two more rigorous trials, in conjunction with our re-analysis of original data suggests that GLM may be superior to placebo for the treatment of mild to moderate OA.[Article]
   

CLINICAL

3. Coulson S1, Vecchio P, Gramotnev H, Vitetta L. Inflammopharmacology. 2012 Apr;20(2):71-6. doi: 10.1007/s10787-012-0128-6. Green-lipped mussel (Perna canaliculus) extract efficacy in knee osteoarthritis and improvement in gastrointestinal dysfunction: a pilot study
   Green-lipped mussel significantly improved knee joint pain, stiffness and mobility. We report for the first time that the administration of GLM extract also significantly improved GI symptoms by 49% in OA patients.[Abstract]
   

CLINICAL

4. Cho SH1, Jung YB, Seong SC, Park HB, Byun KY, Lee DC, Song EK, Son JH. Eur Ann Allergy Clin Immunol. 2003 Jun;35(6):212-6. Clinical efficacy and safety of Lyprinol, a patented extract from New Zealand green-lipped mussel (Perna Canaliculus) in patients with osteoarthritis of the hip and knee: a multicenter 2-month clinical trial
   Lyprinol was very effective and is a promising anti-inflammatory product that relieves the signs and symptoms of osteoarthritis, without adverse effect.[Abstract]
   

RCT

5. Zawadzki M1, Janosch C, Szechinski J. Mar Drugs. 2013 Jun 5;11(6):1920-35. doi: 10.3390/md11061920. Perna canaliculus lipid complex PCSO-524™ demonstrated pain relief for osteoarthritis patients benchmarked against fish oil, a randomized trial, without placebo control
   These results suggest that PCSO-524™ might offer a potential alternative complementary therapy with no side effects for OA patients.[Article]
   

REVIEW

6. Halpern GM1. Allerg Immunol (Paris). 2000 Sep;32(7):272-8. Anti-inflammatory effects of a stabilized lipid extract of Perna canaliculus (Lyprinol)
   Clinical studies, either controlled or randomized, have demonstrated very significant AI activity in patients with osteoarthritis (OA), rheumatoid arthritis (RA), asthma, and other inflammatory conditions. Lyprinol is a reproducible, stable source of bioactive lipids with much greater potency than plant/marine oils currently used as nutritional supplements to ameliorate signs of inflammation.[Abstract]
   

RCT Animal

7. Cayzer J1, Hedderley D, Gray S. Equine Vet J. 2012 Jul;44(4):393-8. doi: 10.1111/j.2042-3306.2011.00455.x. A randomised, double-blinded, placebo-controlled study on the efficacy of a unique extract of green-lipped mussel (Perna canaliculus) in horses with chronic fetlock lameness attributed to osteoarthritis
   The LPPC significantly alleviated the severity of lameness and joint pain and improved response to joint flexion in horses with lameness attributable to OA in the fetlock.[Abstract]
   

RCT Animal

8. Pollard B1, Guilford WG, Ankenbauer-Perkins KL, Hedderley D. N Z Vet J. 2006 Jun;54(3): Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease
   GLME had a beneficial effect on the clinical signs of dogs presumptively diagnosed with mild-to-moderate DJD. Long-term therapy may be required before improvement is apparent.[Abstract]
   

Kurkuma

REVIEW

1. Mirzaei H1, Shakeri A2, Rashidi B3, Jalili A1, Banikazemi Z4, Sahebkar A5. Biomed Pharmacother. 2017 Jan;85:102-112. doi: 10.1016/j.biopha.2016.11.098 Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies
   The efficacy and safety of curcumin phytosomes have been shown against several human diseases including cancer, osteoarthritis, diabetic microangiopathy and retinopathy, and inflammatory diseases.[Abstract]
   

REVIEW

2. Peddada KV1, Peddada KV2, Shukla SK3, Mishra A3, Verma V4. Orthop Surg. 2015 Aug;7(3):222-31. doi: 10.1111/os.12183. Role of Curcumin in Common Musculoskeletal Disorders: a Review of Current Laboratory, Translational, and Clinical Dat
   Research at the laboratory, translational and clinical levels that supports the use of curcumin for various musculoskeletal disorders, such as osteoarthritis, osteoporosis, musculocartilaginous disorders, and sarcoma is here in comprehensively summarized.[Abstract]
   

REVIEW

3. Henrotin Y1, Clutterbuck AL, Allaway D, Lodwig EM, Harris P, Mathy-Hartert M, Shakibaei M, Mobasheri A. Osteoarthritis Cartilage. 2010 Feb;18(2):141-9. doi: 10.1016/j.joca.2009.10.002
   The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals.[Abstract]
   

CLINICAL

4. Panahi Y1, Alishiri GH2, Parvin S1, Sahebkar A3,4. J Diet Suppl. 2016;13(2):209-20. doi: 10.3109/19390211.2015.1008611. Mitigation of Systemic Oxidative Stress by Curcuminoids in Osteoarthritis: Results of a Randomized Controlled Trial
   Short-term supplementation with curcuminoids attenuates systemic oxidative stress in patients with osteoarthritis. These antioxidant effects may account for the reported therapeutic effects of curcuminoids in relieving osteoarthritis symptoms.[Abstract]
   

CLINICAL

5. Henrotin Y1, Gharbi M, Dierckxsens Y, Priem F, Marty M, Seidel L, Albert A, Heuse E, Bonnet V, Castermans C. BMC Complement Altern Med. 2014 May 17;14:159. doi: 10.1186/1472-6882-14-159. Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial
   This study highlighted the potential effect of curcumin in knee OA patient. This effect was reflected by the variation of a cartilage specific biomarker, Coll2-1 that was rapidly affected by the treatment. These results are encouraging for the qualification of Coll2-1 as a biomarker for the evaluation of curcumin in OA treatment.[Article]
   

RCT

6. Panahi Y1, Rahimnia AR, Sharafi M, Alishiri G, Saburi A, Sahebkar A. Phytother Res. 2014 Nov;28(11):1625-31. doi: 10.1002/ptr.5174. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial
   To conclude, curcuminoids represent an effective and safe alternative treatment for OA.[Abstract]
   

RCT

7. Kuptniratsaikul V1, Dajpratham P1, Taechaarpornkul W2, Buntragulpoontawee M3, Lukkanapichonchut P4, Chootip C5, Saengsuwan J6, Tantayakom K7, Laongpech S8. Clin Interv Aging. 2014 Mar 20;9:451-8. doi: 10.2147/CIA.S58535. eCollection 2014. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study
   C. domestica extracts are as effective as ibuprofen for the treatment of knee osteoarthritis.[Article]
   

ANIMAL

8. Martins CA1, Leyhausen G1, Volk J1, Geurtsen W2. J Endod. 2015 Oct;41(10):1638-45. doi: 10.1016/j.joen.2015.05.009. Curcumin in Combination with Piperine Suppresses Osteoclastogenesis In Vitro
   Piperine, an alkaloid present in black pepper, seems to enhance the bioavailability and activity of curcumin.[Abstract]
   

ANIMAL

9. Zeng X1,2, Cai D1,2, Zeng Q3,4, Chen Z1,2, Zhong G5, Zhuo J1,4, Gan H1,2, Huang X1,2, Zhao Z1,2, Yao N1,2, Huang D1,2, Zhang C1,4, Sun D1,2, Chen Y1,2. Biopharm Drug Dispos. 2017 Jan;38(1):3-19. doi: 10.1002/bdd.2049. Selective reduction in the expression of UGTs and SULTs, a novel mechanism by which piperine enhances the bioavailability of curcumin in rat
   It is concluded that piperine pre-treatment time-dependently improves the bioavailability of curcumin.[Abstract]
   

REVIEW

10. Anand P1, Kunnumakkara AB, Newman RA, Aggarwal BB. Mol Pharm. 2007 Nov-Dec;4(6):807-18. Epub 2007 Nov 14. Bioavailability of curcumin: problems and promises
    These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life.[Abstract]
    

Referenties vitamine C

1. 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
   
   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. 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. 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).
2. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study
   
   A 16-week randomized, double-blind, placebo-controlled crossover trial of a combination of glucosamine HCl (1,500 mg/day), chondroitin sulfate (1,200 mg/day), and manganese ascorbate (228 mg/day) in degenerative joint disease (DJD) of the knee or low back was conducted. The combination therapy relieves symptoms of knee osteoarthritis. A larger data set is needed to determine the value of this therapy for spinal DJD. Short-term combination therapy appears safe in this setting.
3. Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis
   
   We recruited 93 patients with OA of the knee from a single center. The intervention group received 1000 mg FCHG49 glucosamine HCl, 800 mg TRH122 low molecular weight sodium chondroitin sulfate and 152 mg manganese ascorbate twice daily The studied combination of glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate was found to be effective for the treatment of radiographically mild to moderate OA of the knee as measured by the ISK. This is the first U.S. study of these agents. Copyright 2000 OsteoArthritis Research Society International.
4. Vitamin C and chiropractic
   
   A review of the literature relating to possible clinical implications of ascorbic acid (AA) supplementation was conducted. Factors requiring a higher AA intake include smoking, alcohol ingestion, stress, diabetes mellitus, pregnancy, and certain drugs, including oral contraceptives, some antibiotics, acetylsalicylate and anti-inflammatory medications. AA has been found to significantly increase wound healing, reduce the inflammatory response, lessen respiratory distress, enhance immune function and serve to benefit many common conditions including osteoarthritis. It is concluded that vitamin C supplementation could be utilized for many conditions seen by chiropractors.
5. Effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate on synovial fluid chondroitin sulfate 3B3 and 7D4 epitope in a canine cruciate ligament transection model of osteoarthritis
   
   Administration of CS-G-M was associated with altered concentrations of 3B3 and 7D4 epitope in synovial fluid, suggesting that these compounds may act to modulate articular cartilage matrix metabolism in vivo
6. Effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate on synovial fluid chondroitin sulfate 3B3 and 7D4 epitope in a canine cruciate ligament transection model of osteoarthritis
   
   Administration of CS-G-M was associated with altered concentrations of 3B3 and 7D4 epitope in synovial fluid, suggesting that these compounds may act to modulate articular cartilage matrix metabolism in vivo
7. 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
   
   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).

Referenties glucosamine

Hieronder vindt u alle wetenschappelijke artikelen die zijn gebruikt bij het schrijven van ons stuk over het gebruik van glucosamine bij artrose.

1. Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials
   The available evidence suggests that glucosamine sulfate may be effective and safe in delaying the progression and improving the symptoms of knee OA. Due to the sparse data on structural efficacy and safety, further studies are warranted.
2. The effect of glucosamine sulphate on osteoarthritis: design of a long-term randomised clinical trial
   The primary outcome measures, which are joint space narrowing (JSN), and change in the pain and function score of the Western Ontario McMaster Universities Osteoarthritis index (WOMAC), are determined at baseline and after two years of follow-up during the final assessment. Intermediate measures at three-month intervals throughout the trial are used to study secondary outcome measures. Secondary outcome measures are changes in WOMAC stiffness score, quality of life, medical consumption, side effects and differences in biomarker CTX-II.
3. The effect of glucosamine supplementation on people experiencing regular knee pain
   These results suggest that glucosamine supplementation can provide some degree of pain relief and improved function in persons who experience regular knee pain, which may be caused by prior cartilage injury and/or osteoarthritis. The trends in the results also suggest that, at a dosage of 2,000 mg per day, the majority of improvements are present after eight weeks.
4. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial
   The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis.
5. Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis
   Similarly, patients given glucosamine sulphate experienced earlier alleviation of symptoms compared with those who had placebo. The use of glucosamine sulphate also resulted in a significantly larger proportion of patients who experienced lessening or disappearance of symptoms within the trial period. No adverse reactions were reported by the patients treated with glucosamine, and no variation in laboratory tests was recorded.
6. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study
   Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification.
7. Therapeutic Activity of Oral Glucosamine Sulfate in Osteoarthrosis: A Placebo-Controlled Double-Blind Investigation
   Those who had glucosamine sulfate showed a picture more similar to healthy cartilage. It is concluded that glucosamine sulfate tends to rebuild the damaged cartilage, thus restoring articular function in most chronic arthrosic patients.
8. Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of the knee in out-patients
   A double-blind trial was carried out in 40 out-patients with unilateral osteoarthrosis of the knee to compare the efficacy and tolerance of oral treatment with 1.5 g glucosamine sulphate or 1.2 g ibuprofen daily over a period of 8 weeks. Pain scores decreased faster during the first 2 weeks in the ibuprofen than in the glucosamine treatment group. Although the rate of decrease was slower, the reduction in pain scores was continued throughout the trial period in patients an glucosamine and the difference between the two groups turned significantly in favour of glucosamine
9. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee
   Topical application of glucosamine and chondroitin sulfate is effective in relieving the pain from OA of the knee and improvement is evident within 4 weeks.
10. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee
    Glucosamine sulfate was therefore as effective as ibuprofen on symptoms of knee OA. These data confirm glucosamine sulfate as a safe symptomatic Slow Acting Drug for OA.
11. The use of glucosamine therapy in osteoarthritis
    Although clinical trials include methodologic flaws and publication bias, glucosamine is likely an effective therapy for the symptomatic management of osteoarthritis.
12. Glucosamine for osteoarthritis: part I, review of the clinical evidence
    The National Center for Complementary and Alternative Medicine and the National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS/NCCAM) have funded a multicenter five arm placebo controlled study called The Glucosamine Arthritis Intervention Trial (GAIT). GAIT spans 24 weeks, enrolling 1588 subjects, at 13 centers comparing the efficacy of glucosamine sulfate, chondroitin sulfate, glucosamine with chondroitin, to placebo and compared to celecoxib for knee OA. This study may have final data in March 2005.
13. Glucosamine for osteoarthritis: part II, biologic and metabolic controversies
    Glucosamine is a popular nutritional supplement, discussed in clinical offices, peer-reviewed literature, and the media. Despite its popularity, much information is still needed regarding its biological effect in-vivo and its effects on glucose metabolism. The biologic effects of other constituents such as sulfate, chondroitin sulfate, and other additives need to be investigated as well.
14. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial
    This study demonstrates that oral glucosamine supplementation does not result in clinically significant alterations in glucose metabolism in patients with type 2 diabetes mellitus.
15. Osteoarthritic patients with high cartilage turnover show increased responsiveness to the cartilage protecting effects of glucosamine sulphate
    The data indicate that measurement of urinary collagen type II C-telopeptide fragments enables the identification of OA patients with high cartilage turnover who at the same time are most responsive to therapy with structure modifying drugs.
16. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis
    Our study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds. Regarding the relatively sparse data on glucosamine and joint space narrowing and the absence of data on structural effects of chondroitin, further studies are needed to investigate the relationship among time, dose, patient baseline characteristics, and structural efficacy for an accurate, disease-modifying characterization of these 2 compounds.
17. Glucosamine: a review of its use in the management of osteoarthritis
    In short-term clinical trials, glucosamine provided effective symptomatic relief for patients with osteoarthritis of the knee. In addition, glucosamine has shown promising results in modifying the progression of arthritis over a 3-year period. Glucosamine may therefore prove to be a useful treatment option for osteoarthritis
18. Recent advances in glucosamine and chondroitin supplementation
    Glucosamine and chondroitin are alternative solutions to previous pharmaceutical options for the treatment of osteoarthritis
19. Medical management of osteoarthritis of the knee and hip joints
    Glucosamine sulfate is a safe and effective over-the-counter treatment
20. Articular cartilage biology
    Current research is helping to clarify the mechanisms by which a variety of agents, such as glucosamine, chondroitin sulfate, hyaluronic acid, green tea, glucocorticoids, and nonsteroidal anti-inflammatory drugs, can modify the symptoms and course of osteoarthritis
21. New perspectives in the management of osteoarthritis. structure modification: facts or fantasy?
    Several entities have been carefully investigated for the symptomatic and structural management of osteoarthritis (OA). The most compelling evidence of a potential for inhibiting the structural progression of OA has been obtained with glucosamine sulfate, while some preliminary results also suggest that other compounds could be used in the same indication. At any rate, several medications have clearly demonstrated a symptomatic action, mainly in OA of the lower limbs, including pain relief and improvement of functional disability. An important issue is that all conclusive studies with such chemical entities resulted from the use of prescription medicines and not over-the-counter or nutriceutical supplements.
22. Chondroprotective agents: glucosamine and chondroitin
    The near universal finding of the safety of glucosamine and chondroitin combined with some compelling evidence of their efficacy should spur further research into their mechanism of action, optimal dosing, long-term effects on disease modification, and clinical applicability. When recommending a supplement to patients, the clinician should take into account the purity of the ingredients, reputation of the manufacturer, and the molecular weight of chondroitin supplied.
23. Glucosamine sulfate in osteoarthritis of the knee
    Glucosamine sulfate is a drug used for the treatment of osteoarthritis (OA), based on its pharmacological and metabolic activities on the cartilage and chondrocytes, complemented by mild anti-inflammatory properties and a favorable pharmacokinetic profile.
24. The effect of glucosamine sulphate on osteoarthritis: design of a long-term randomised clinical trial
    Pharmacological treatment for osteoarthritis (OA) can be divided into two groups: symptom-modifying drugs and disease-modifying drugs. Symptom-modifying drugs are currently the prescription of choice for patients with OA, as disease-modifying drugs are not yet available in usual care. However, there has recently been a lot of debate about glucosamine sulphate (GS), a biological agent that is thought to have both symptom-modifying and disease-modifying properties.
25. Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies
    To investigate the effect of glucosamine sulfate on long-term symptoms and structure progression in postmenopausal women with knee osteoarthritis (OA). 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.
26. Correlation between radiographic severity of knee osteoarthritis and future disease progression. Results from a 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate
    These results suggest that patients with the less severe radiographic knee OA will experience, over 3 years, the most dramatic disease progression in terms of joint space narrowing. Such patients may be particularly responsive to structure-modifying drugs.
27. Glucosamine for osteoarthritis Patients’ welfare should be primary concern
    Glucosamine is currently the only substance known that can both help with the symptoms of osteoarthritis and improve the course of the disease, without showing any harmful effect for the patient. Despite its supplement status in certain countries, the evidence tells us that glucosamine must be taken seriously.
28. Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial
    GS and ibuprofen reduce pain levels in patients with TMJ degenerative joint disease. In the subgroup that met the initial efficacy criteria, GS had a significantly greater influence in reducing pain produced during function and effect of pain with daily activities. GS has a carryover effect.
29. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study
    A 16-week randomized, double-blind, placebo-controlled crossover trial of a combination of glucosamine HCl (1,500 mg/day), chondroitin sulfate (1,200 mg/day), and manganese ascorbate (228 mg/day) in degenerative joint disease (DJD) of the knee or low back was conducted. CONCLUSIONS: The combination therapy relieves symptoms of knee osteoarthritis.
30. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis
    The present study confirms that GS is a selective drug for osteoarthritis, as effective on the symptoms of the disease as NSAIDs but significantly better tolerated. For these properties GS seems particularly indicated in the long-term treatments needed in osteoarthritis.
31. Glucosamine sulphate: a controlled clinical investigation in arthrosis
    Efficacy and tolerance of a new preparation of pure glucosamine sulphate, in injectable and oral form, were investigated in 30 patients with osteoarthrosis. Clinical and biological tolerance were excellent with both treatments, and no definitely drug-related complaints were recorded. It is suggested that parenteral and/or oral treatment with pure glucosamine sulphate should be considered as basic therapy for the management of primary or secondary degenerative osteoarthrosis disorders.
32. Risk assessment for glucosamine and chondroitin sulfate
    Glucosamine and chondroitin sulfate are two popular dietary ingredients present in dietary supplements intended to support joint health. A large body of human and animal research suggests that oral intakes of these ingredients, either alone or in combination, reduces joint pain and improves mobility in persons with osteoarthritis. The OSL risk assessment method indicates that the evidence strongly supports safety at intakes up to 2000mg/d for glucosamine, and 1200mg/d for chondroitin sulfate, and these levels are identified as the respective OSL. These values represent the highest levels tested in human clinical trials. The complete absence of adverse effects at these levels supports a confident conclusion of their long-term safety.
33. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee
    Glucosamine sulfate is able to stimulate proteoglycan synthesis by chondrocytes and has mild anti-inflammatory properties. In clinical trials, glucosamine sulfate was more effective than placebo in controlling the symptoms of osteoarthritis (OA). Glucosamine sulfate was therefore as effective as ibuprofen on symptoms of knee OA. These data confirm glucosamine sulfate as a safe symptomatic Slow Acting Drug for OA.
34. Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis
    Glu, MSM and their combination produced an analgesic and anti-inflammatory effect in osteoarthritis. Combination therapy showed better efficacy in reducing pain and swelling and in improving the functional ability of joints than the individual agents. All the treatments were well tolerated. The onset of analgesic and anti-inflammatory activity was found to be more rapid with the combination than with Glu. It can be concluded that the combination of MSM with Glu provides better and more rapid improvement in patients with osteoarthritis.
35. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator
    The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms. Although acetaminophen also had a higher responder rate compared with placebo, it failed to show significant effects on the algofunctional indexes.
36. Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects
    When compared with placebo, glucosamine did not cause insulin resistance or endothelial dysfunction in lean subjects or significantly worsen these findings in obese subjects. The half-life of plasma glucosamine after oral dosing was approximately 150 min, with no significant changes in steady-state glucosamine levels detectable after 6 weeks of therapy. We conclude that oral glucosamine at standard doses for 6 weeks does not cause or significantly worsen insulin resistance or endothelial dysfunction in lean or obese subjects.
37. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial
    
    The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis.
38. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy
    There were no adverse effects of oral glucosamine administration on blood, urine or fecal parameters. Side effects were significantly less common with glucosamine than placebo or non-steroidal anti-inflammatory drugs (NSAID). In contrast to NSAID, no serious or fatal side effects have been reported for glucosamine. Our critical evaluation indicates that glucosamine is safe under current conditions of use and does not affect glucose metabolism.
39. Sulfated glucosamine inhibits MMP-2 and MMP-9 expressions in human fibrosarcoma cells
    In the present study, sulfated glucosamine (SGlc) that has been reported to relieve joint pain and inflammation in many arthritis patients was studied for its inhibitory effects on MMP-2 and MMP-9 in human fibrosarcoma cells. Expression and activity of above MMPs studied using gelatin zymography suggested SGlc as a potent MMP inhibitor. Further, transfection of promoter genes of MMPs and their transcription factors clearly exhibited that inhibition of MMP-2 and MMP-9 was due to down-regulation of transcription factor, NF-kappaB. However expression of activator protein-1 (AP-1), another important transcription factor of MMPs, was not affected by SGlc treatment. In addition, protein expression results of Western blot analysis were also in agreement with the results of gene transfection experiments. Moreover, down-regulation of NF-kappaB resulted in production of low levels of both NF-kappaB p50 and p65 proteins and directly affected activation process of MMP-2 and MMP-9 expressions. Since MMPs involve in joint inflammation, it can be presumed that inhibition of MMP-2 and MMP-9 can be one of the mechanisms of SGlc to be an effective drug in relieving the symptoms of osteoarthritis.
40. N-Acetylglucosamine Prevents IL-1″-Mediated Activation of Human Chondrocytes
    Glucosamine represents one of the most commonly used drugs to treat osteoarthritis. However, mechanisms of its antiarthritic activities are still poorly understood. The present study identifies a novel mechanism of glucosamine-mediated anti-inflammatory activity. It is shown that both glucosamine and N-acetylglucosamine inhibit IL-1-induced NO production in normal human articular chondrocytes.
41. The reverse glucosamine sulfate pathway: application in knee osteoarthritis
    Glucosamine is a natural amino sugar and a normal constituent of glycosaminoglycans in the cartilage matrix and synovial fluid of joints. Crystalline glucosamine sulfate salt has been approved as a medicinal product for the treatment of osteoarthritis in several European countries. The activity of glucosamine sulfate has recently been related to its capacity to downregulate the catabolic effects of pro-inflammatory molecules, such as IL-1, which are present in osteoarthritic cartilage.
42. Glucosamine sulfate promotes osteoblastic differentiation of MG-63 cells via anti-inflammatory effect
    Glucosamine sulfate (SGlc) has been known to be effective in controlling osteoarthritis (OA) symptoms in several clinical studies. However, the mechanisms of this positive effect of SGlc in human OA still remain elusive. Therefore, first, the effects of SGlc on the differentiation of osteoblast-like MG-63 cells were investigated. Our results demonstrate that SGlc can increase ALP activity, collagen synthesis, osteocalcin secretion, and mineralization in osteoblastic cells in vitro. Furthermore, it was observed that SGlc exhibited anti-inflammatory effect on production of TNF-alpha, IL-1beta, and PGE(2) in macrophage, RAW264.7 cells. In conclusion, these results suggest that SGlc can promote cell differentiation in cultured MG-63 osteoblast cells via anti-inflammatory effect.
43. Glucosamine modulates chondrocyte proliferation, matrix synthesis, and gene expression
    Results indicate that culture conditions play a significant role in determining the effect of GlcN on chondrocytes, explaining both the previously reported beneficial and deleterious effects of this sugar. The ability of GlcN to alter TGF-beta1 signaling provides a biochemical mechanism for GlcN activity on chondrocytes that up to now has remained elusive. The observed anabolic effect of optimal GlcN concentrations on chondrocytes may be useful in formulating effective cartilage repair strategies.
44. Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes
    The results indicate that GS can stimulate mRNA and protein levels of aggrecan core protein and, at the same time, inhibit production and enzymatic activity of matrix-degrading MMP-3 in chondrocytes from OA articular cartilage. These results provide a cogent molecular mechanism to support clinical observations suggesting that GS may have a beneficial effect in the prevention of articular cartilage loss in some patients with OA.
45. This house believes that we should advise our patients with osteoarthritis of the knee to take glucosamine
    Glucosamine is a natural aminomonosaccharide, which is a normal constituent of glycosaminoglycans in cartilage matrix and synovial fluid. Oral glucosamine is taken by patients with osteoarthritis in the belief that it can improve symptoms and act as a disease-modifying agent. There are good biological reasons to believe that glucosamine could have beneficial effects on cartilage in osteoarthritis. Experiments on cultured human chondrocytes have shown that glucosamine increases the production of aggrecans, and reduces the formation of nitric oxide and interleukin 6 in response to interleukin 1ß. It may therefore exert both chondroprotective and anti-inflammatory effects. Furthermore, experiments in animals have suggested that circulating glucosamine can localize in cartilage.
    
46. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy
    There were no adverse effects of oral glucosamine administration on blood, urine or fecal parameters. Side effects were significantly less common with glucosamine than placebo or non-steroidal anti-inflammatory drugs (NSAID). In contrast to NSAID, no serious or fatal side effects have been reported for glucosamine. Our critical evaluation indicates that glucosamine is safe under current conditions of use and does not affect glucose metabolism.
47. Pandemonium over painkillers persists
    Chronic non-cancer pain remains under-treated. Five years ago it was highlighted that more research was needed into the safety and efficacy of NSAIDs and opioid drugs in older people (Cowan, 2002). Concerns remain over NSAID-induced pathology and now there are safety concerns over the continued use of supposedly safer COX-2 agents. There also remain concerns over the problematic use of opioids, including the potential for psychological and physical dependence. While more research is still needed to inform prescribing for older people, it is also apparent that we still need long-term studies of commonly used pain medications for the whole spectrum of age groups. Data derived from such studies would inform nurse prescribing.
48. ACETAMINOPHEN-INDUCED HEPATOTOXICITY
    The analgesic acetaminophen causes a potentially fatal, hepatic centrilobular necrosis when taken in overdose. The initial phases of toxicity were described in Dr. Gillette’s laboratory in the 1970s. These findings indicated that acetaminophen was metabolically activated by cytochrome P450 enzymes to a reactive metabolite that depleted glutathione (GSH) and covalently bound to protein.
49. Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man
    Glucosamine is bioavailable after oral administration of crystalline glucosamine sulfate, persists in circulation, and its pharmacokinetics support once-daily dosage. Steady state peak concentrations at the therapeutic dose of 1,500 mg were in line with those found to be effective in selected in vitro mechanistic studies. This is the only glucosamine formulation for which pharmacokinetic, efficacy and safety data are now available.
50. The effect of glucosamine sulphate on osteoarthritis: design of a long-term randomised clinical trial
    Pharmacological treatment for osteoarthritis (OA) can be divided into two groups: symptom-modifying drugs and disease-modifying drugs. Symptom-modifying drugs are currently the prescription of choice for patients with OA, as disease-modifying drugs are not yet available in usual care. However, there has recently been a lot of debate about glucosamine sulphate (GS), a biological agent that is thought to have both symptom-modifying and disease-modifying properties.
51. Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials
    The available evidence suggests that glucosamine sulfate may be effective and safe in delaying the progression and improving the symptoms of knee OA. Due to the sparse data on structural efficacy and safety, further studies are warranted.
52. Glucosamine modulates chondrocyte proliferation, matrix synthesis, and gene expression
    Results indicate that culture conditions play a significant role in determining the effect of GlcN on chondrocytes, explaining both the previously reported beneficial and deleterious effects of this sugar. The ability of GlcN to alter TGF-beta1 signaling provides a biochemical mechanism for GlcN activity on chondrocytes that up to now has remained elusive. The observed anabolic effect of optimal GlcN concentrations on chondrocytes may be useful in formulating effective cartilage repair strategies.
53. N-acylation of glucosamine modulates chondrocyte growth, proteoglycan synthesis, and gene expression
    Addition of GlcNBu to BAC or HAC to AD cultures generally stimulated cell proliferation and PG synthesis, while addition of GlcN resulted in inhibition of these indicators. The inhibitory effects of the GlcN molecule appear to be related to the unsubstituted amino group. Additions of GlcNBu, but not GlcN, to HAC resulted in upregulation in the expression of a large number of genes.
54. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial
    The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis.
55. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee
    Glucosamine sulfate is able to stimulate proteoglycan synthesis by chondrocytes and has mild anti-inflammatory properties. In clinical trials, glucosamine sulfate was more effective than placebo in controlling the symptoms of osteoarthritis (OA). In order to better characterize this therapeutic activity, we conducted a randomized, double-blind, parallel-group study of glucosamine sulfate 500 mg t.i.d. vs ibuprofen 400 mg t.i.d., orally for 4 weeks. Glucosamine sulfate was therefore as effective as ibuprofen on symptoms of knee OA. These data confirm glucosamine sulfate as a safe symptomatic Slow Acting Drug for OA.
56. Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis
    The efficacy and tolerance of oral glucosamine sulphate were tested against placebo in a prospective double-blind trial in 20 out-patients with established osteoarthrosis. Two capsules of either glucosaminene sulphate (250 mg) or placebo were administered 3-times daily over a period of 6 to 8 weeks. Articular pain, joint tenderness and restricted movement were semi-quantitatively scored 1 to 4 every 3 days, and individually averaged over the treatment period (overall composite score). Possible side-reactions were similarly scored upon positive questioning of the patients. Haematology, erythrocyte sedimentation rate, urine analysis and X-rays were recorded before and after treatment. Significant alleviation of symptoms was associated with the use of the active drug at the prescribed dose. Similarly, patients given glucosamine sulphate experienced earlier alleviation of symptoms compared with those who had placebo. The use of glucosamine sulphate also resulted in a significantly larger proportion of patients who experienced lessening or disappearance of symptoms within the trial period. No adverse reactions were reported by the patients treated with glucosamine, and no variation in laboratory tests was recorded.
57. Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis
    Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification
58. Therapeutic Activity of Oral Glucosamine Sulfate in Osteoarthrosis: A Placebo-Controlled Double-Blind Investigation
    It is concluded that glucosamine sulfate tends to rebuild the damaged cartilage, thus restoring articular function in most chronic arthrosic patients.
59. The effect of glucosamine supplementation on people experiencing regular knee pain
    These results suggest that glucosamine supplementation can provide some degree of pain relief and improved function in persons who experience regular knee pain, which may be caused by prior cartilage injury and/or osteoarthritis. The trends in the results also suggest that, at a dosage of 2000 mg per day, the majority of improvements are present after eight weeks.
60. The Effect of Glucosamine-Chondroitin Supplementation on Glycosylated Hemoglobin Levels in Patients With Type 2 Diabetes Mellitus
    This study demonstrates that oral glucosamine supplementation does not result in clinically significant alterations in glucose metabolism in patients with type 2 diabetes mellitus.
61. Oral Glucosamine for 6 Weeks at Standard Doses Does Not Cause or Worsen Insulin Resistance or Endothelial Dysfunction in Lean or Obese Subjects
    We conclude that oral glucosamine at standard doses for 6 weeks does not cause or significantly worsen insulin resistance or endothelial dysfunction in lean or obese subjects.
62. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate
    Topical application of glucosamine and chondroitin sulfate is effective in relieving the pain from OA of the knee and improvement is evident within 4 weeks.

Referenties chondroïtine

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1. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo
   This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA
2. Chondroitin sulfate in osteoarthritis of the knee: a prospective, double blind, placebo controlled multicenter clinical study
   We observed a trend towards efficacy of CS 1 g/day compared to placebo with good tolerability after 3 month treatment, and persistent efficacy one month posttreatment. Further investigations are required to confirm this trend.
3. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis
   CS may be useful in OA, but further investigations in larger cohorts of patients for longer time periods are needed to prove its usefulness as a symptom modifying drug in OA.
4. Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study
   These results confirm that oral chondroitin 4- and 6-sulfate is an effective and safe symptomatic slow-acting drug for the treatment of knee OA. In addition, CS might be able to stabilize the joint space width and to modulate bone and joint metabolism. This is the first preliminary demonstration that a SYSADOA might influence the natural course of OA in humans.
5. Chondroitin sulfate: S/DMOAD (structure/disease modifying anti-osteoarthritis drug) in the treatment of finger joint OA
   In the CS 4&6 group we observed a significant decrease in the number of patients with new ‘erosive’ OA finger joints. This result is particularly important since OA of the finger joints becomes a clinical problem (pain, functional loss) when ‘S’ joints progress to ‘J’ and especially ‘E’ phases.
6. Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis
   Efficacy judgements were significant in favor of the CS group. Both treatments were very well tolerated. All these results strongly suggest that chondroitin sulfate acts as a symptomatic slow-acting drug in knee OA.
7. Results of a multicenter study of chondroitin sulfate (Condrosulf) use in arthroses of the finger, knee and hip joints
   In conclusion it could be demonstrated that a significant reduction of the daily NSAID consumption was possible by concomitant CS-therapy, without the risk of deterioration of the patients’ symptoms. The 97% compliance does not give evidence for drop-out bias. Moreover, the results of this trial are comparable to other international double-blind, in part placebo-controlled studies, concerning CS-therapy, indicating beneficial results in the treatment of osteoarthritis.
8. A two-year study of chondroitin sulfate in erosive osteoarthritis of the hands: behavior of erosions, osteophytes, pain and hand dysfunction
   The untreated group showed significant worsening in erosion, Heberden and Bouchard nodes, Dreiser index and physician and patient global assessment scores. This study confirms the partial efficacy of oral CHS in improving some aspects of EOA.
9. Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in healthy male volunteers
   Ichthyic CS is absorbed slowly, with a t(max)=8.7+/-4.5h and the C(max)averaged 4.87+/-2.05 microg/ml. The differences in the absorption and bioavailability of the various CS formulations is strongly influenced by the structure and characteristics, such as molecular mass, charge density, and cluster of disulfated disaccharides, of the parental molecules.
10. Glucosamine and chondroitin sulfate: biological response modifiers of chondrocytes under simulated conditions of joint stress
    The metabolic response of cartilage from aged animals to glcN and CS under simulated conditions of in vivo stress is significantly greater than that seen in nonstressed or young tissue. By enhancing the “protective” metabolic response of chondrocytes to stress, glcN and CS may improve its ability for repair and regeneration. These observations suggest that these compounds function as biological response modifiers (BRMs), agents which boost natural protective responses of tissues under adverse environmental conditions.
11. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis
    Following patients to 120 or more days, CS was shown to be significantly superior to placebo with respect to the Lequesne index and pain VAS. Pooled data confirmed these results and showed at least 50% improvement in the study variables in the CS group compared to placebo.
12. Nutraceutical therapies for degenerative joint diseases: a critical review
    There is growing recognition of the importance of nutritional factors in the maintenance of bone and joint health, and that nutritional imbalance combined with endocrine abnormalities may be involved in the pathogenesis of osteoarthritis (OA) and osteochondritis dissecans (OCD). Articular cartilage is critically dependent upon the regular provision of nutrients (glucose and amino acids), vitamins (particularly vitamin C), and essential trace elements (zinc, magnesium, and copper). Therefore, dietary supplementation programs and nutraceuticals used in conjunction with non-steroidal, anti-inflammatory drugs (NSAIDs) may offer significant benefits to patients with joint disorders, such as OA and OCD.
13. The pathobiology of osteoarthritis and the rationale for using the chondroitin sulfate for its treatment
    Structure-modifying osteoarthritis (OA) drugs are agents that reverse, retard, or stabilize the pathology of OA, thereby providing symptomatic relief in the long-term treatment. The objective of this review is to evaluate the literature on chondroitin sulfate (CS) with respect to the pathobiology of OA to ascertain whether this agent should be classified as a symptomatic slow-acting drug Many literature data show that CS could have an anti-inflammatory activity and a chondroprotective action by modifying the structure of cartilage. These properties are also related to the oral adsorption of this molecule as high-molecular mass compounds having clusters of sulfate groups and high charge density capable of exert their chondroprotective activity in vivo.
14. Naturocetic (glucosamine and chondroitin sulfate) compounds as structure-modifying drugs in the treatment of osteoarthritis
    The most compelling evidence of a potential for inhibiting the structural progression of osteoarthritis has been obtained with glucosamine sulfate, whereas preliminary results obtained in patients with osteoarthritis of the hands also suggest that chondroitin sulfate could be used in the same indication. Glucosamine sulfate has demonstrated its ability to reduce the progression of osteoarthritis in the lower limbs. The preliminary results obtained in the hands suggest that chondroitin sulfate could also be of interest in this indication.
15. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis
    Our study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds.
16. Glucosamine and chondroitin sulfate are effective in the management of osteoarthritis
    However, for the nutriceuticals evaluated here, there is abundant in vitro, in vivo, animal clinical, and human clinical evidence of both their efficacy and safety. They deserve a prominent place in the armamentarium of nonsurgical treatment of osteoarthritis.
17. Glucosamine and chondroitin sulfates in the treatment of osteoarthritis: a survey
    For more than 30 years, non-steroidal anti-inflammatory drugs (NSAIDs) have been used as standards in the treatment of osteoarthritis (OA). Serious and often life-threatening adverse effects due to these agents are common. Clinical findings have revealed that glucosamine sulfate and chondroitin sulfate are effective and safer alternatives to alleviate symptoms of OA.
18. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis
    Trials of glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects.
19. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate
    A meta-analysis of chondroitin sulfate trials has also been published. Of the 12 published trials, 4 randomized double-blind placebo or NSAID-controlled trials with 227 patients on chondroitin sulfate were entered into the analysis. All four studies showed chondroitin sulfate to be superior to placebo, with respect to Lequesne index, visual analog scale for pain and medication consumption. Significant changes (P < or = .05) were seen in those treated from day 60 to the study endpoints (150 to 180 days). Pooled data demonstrated at least 50% improvement in the study variables in the chondroitin treated group.
20. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate
    A meta-analysis of chondroitin sulfate trials has also been published. Of the 12 published trials, 4 randomized double-blind placebo or NSAID-controlled trials with 227 patients on chondroitin sulfate were entered into the analysis. All four studies showed chondroitin sulfate to be superior to placebo, with respect to Lequesne index, visual analog scale for pain and medication consumption. Significant changes (P < or = .05) were seen in those treated from day 60 to the study endpoints (150 to 180 days). Pooled data demonstrated at least 50% improvement in the study variables in the chondroitin treated group.
21. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial
    While there was no significant symptomatic effect in this study, long-term treatment with CS may retard radiographic progression in patients with OA of the knee. However, the clinical relevance of the observed structural results has to be further evaluated, and further studies are needed to confirm the structural effects of CS.
22. Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis
    CS seems to have slow but gradually increasing clinical activity in OA; these benefits last for a long period after the end of treatment.
23. Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 x 400 mg/day vs placebo
    In conclusion, these results indicate that CS favours the improvement of the subjective symptoms, improving the joint mobility. An additional consideration is that the efficacy of 1200 mg CS as a single daily dose does not differ from that of 3 x 400 mg daily doses of CS for all the clinical parameters taken into consideration
24. A new mechanism of action of chondroitin sulfates ACS4-ACS6 in osteoarthritic cartilage
    It has been demonstrated that ACS4-ACS6 are capable of neutralizing the enhanced catabolic capacity of activated human OA chondrocytes.
25. Cartilage proteoglycans
    The predominant proteoglycan present in cartilage is the large chondroitin sulfate proteoglycan ‘aggrecan’. Following its secretion, aggrecan self-assembles into a supramolecular structure with as many as 50 monomers bound to a filament of hyaluronan.
26. Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1-challenged bovine articular cartilage explants
    GLN and CS, at concentrations that are within the range measured in synovial fluid and blood after oral administration, may regulate expression of matrix degrading enzymes and their inhibitors at the transcriptional level, providing a plausible mechanism for their purported chondroprotective properties
27. Chondroitin sulfate modulation of matrix and inflammatory gene expression in IL-1beta-stimulated chondrocytes – study in hypoxic alginate bead cultures
    These data suggest that CS may exert both chondroprotective and anti-inflammatory limited effects on articular cartilage that could have long-term beneficial action on the osteoarthritic process.
28. Effects of glucosamine and chondroitin sulfate on bovine cartilage explants under long-term culture conditions
    Treatment with GLN and CS consistently downregulated mRNA expression for inflammatory mediators and matrix degrading enzymes while increasing TIMP-3 transcripts
29. Wetenschappelijk onderzoek artrose – chondroitine
    
30. The pathobiology of osteoarthritis and the rationale for using the chondroitin sulfate for its treatment
    CS exhibits a wide range of biological activities and from a pharmacological point of view it produces a slow but gradual decrease of the clinical symptoms of OA and these benefits last for a long period after the end of treatment. Many literature data show that CS could have an anti-inflammatory activity and a chondroprotective action by modifying the structure of cartilage. These properties are also related to the oral adsorption of this molecule as high-molecular mass compounds having clusters of sulfate groups and high charge density capable of exert their chondroprotective activity in vivo.
31. Pandemonium over painkillers persists
    Chronic non-cancer pain remains under-treated. Five years ago it was highlighted that more research was needed into the safety and efficacy of NSAIDs and opioid drugs in older people (Cowan, 2002). Concerns remain over NSAID-induced pathology and now there are safety concerns over the continued use of supposedly safer COX-2 agents. There also remain concerns over the problematic use of opioids, including the potential for psychological and physical dependence. While more research is still needed to inform prescribing for older people, it is also apparent that we still need long-term studies of commonly used pain medications for the whole spectrum of age groups. Data derived from such studies would inform nurse prescribing.
32. Mixtures of glucosamine and chondroitin sulfate reverse fibronectin fragment mediated damage to cartilage more effectively than either agent alone
    GluNH(2) and CS act synergistically in reversing damage and promoting repair at concentrations found in plasma after oral ingestion of these agents. Reversal of PG synthesis suppression correlates more with these activities than suppression of MMP-3 or -13 expression.

Referenties SAMe

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1. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis
   SAMe appears to be as effective as NSAIDs in reducing pain and improving functional limitation in patients with OA without the adverse effects often associated with NSAID therapies.
2. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside–molecular basis of a pleiotrophic molecule
   S-Adenosyl-L-methionine (SAMe), a metabolite present in all living cells, plays a central role in cellular biochemistry as a precursor to methylation, aminopropylation, and transsulfuration pathways. As such, SAMe has been studied extensively since its chemical structure was first described in 1952. Decades of research on the biochemical and molecular roles of SAMe in cellular metabolism have provided an extensive foundation for its use in clinical studies, including those on depression, dementia, vacuolar myelopathy, liver disease, and osteoarthritis. This article provides an overview of the biochemical, molecular, and therapeutic effects of this pleiotrophic molecule.
3. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease
   SAMe administered orally at a dose of 1,200 mg daily was shown to exert the same analgesic activity as naproxen at a dose of 750 mg daily. Tolerability of SAMe was significantly better than that of naproxen, both in terms of physicians’ (p less than 0.025) and patients’ (p less than 0.01) judgments and in terms of the number of patients with side effects (p less than 0.05).
4. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis
   Thirty-six subjects with osteoarthritis of the knee, the hip, and/or the spine were enrolled in a randomized double-blind study. Patients received a daily oral dose of 1,200 mg of S-adenosylmethionine (SAMe) or 1,200 mg of ibuprofen for four weeks. Morning stiffness, pain at rest, pain on motion, crepitus, swelling, and limitation of motion of the affected joints were assessed before and after treatment. The total score obtained by the evaluation of all the individual clinical parameters improved to the same extent in patients treated with SAMe or ibuprofen. Both treatments were well tolerated and no patient from either group withdrew from the study.
5. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis
   In a randomized double-blind study, 36 patients with osteoarthritis of the knee, hip, and/or spine were treated orally with a daily dose of S-adenosylmethionine (SAMe)(1,200 mg) or indomethacin (150 mg) over a period of four weeks. Pretreatment and posttreatment clinical parameters were determined and assessed according to a standard scoring system. SAMe therapy significantly improved the total score obtained by the sum of all clinical findings, as compared with pretreatment values. Similar improvement was evident in indomethacin-treated subjects. Two patients in the SAMe group reported slight nausea after two weeks of therapy, whereas adverse effects developed in seven patients in the indomethacin group
6. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis
   The patients received 600 mg of SAMe daily (equivalent to three tablets of 200 mg each) for the first two weeks and thereafter 400 mg daily (equivalent to two tablets of 200 mg each) until the end of the 24th month of treatment. SAMe administration showed good clinical effectiveness and was well tolerated. The improvement of the clinical symptoms during therapy with SAMe was already evident after the first weeks of treatment and continued up to the end of the 24th month. Non-specific side effects occurred in 20 patients, but in no case did therapy have to be discontinued. Most side effects disappeared during the course of therapy. Moreover, during the last six months of treatment, no adverse effect was recorded.
7. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis
   A double-blind, randomized, 84-day controlled clinical trial was carried out to compare orally administered S-adenosylmethionine (SAMe) (1,200 mg per day) with oral piroxicam therapy (20 mg per day) in the management of unilateral knee osteoarthritis. The ability of each drug to maintain the results achieved at the end of the treatment period was also evaluated during a 56-day follow-up period. Forty-five patients completed the study, 22 in the SAMe group and 23 in the piroxicam group. Both SAMe and piroxicam proved effective in inducing a significant improvement in the total pain score after 28 days of treatment. With regard to the other clinical parameters (i.e., morning stiffness, the distance walked before the onset of pain, active and passive motility), improvement started from about Day 56 in both groups. No significant difference was found between the two treatments in terms of efficacy and tolerability. Patients treated with SAMe maintained clinical improvement achieved at the end of treatment longer than did patients receiving piroxicam
8. S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial
   SAMe has a slower onset of action but is as effective as celecoxib in the management of symptoms of knee osteoarthritis. Longer studies are needed to evaluate the long-term effectiveness of SAMe and the optimal dose to be used.

Referenties Vitamine D

1. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study
   Evidence suggests that pathophysiologic processes in bone are important determinants of outcome in osteoarthritis of the knee. Low intake and low serum levels of vitamin D may compromise favorable responses of bone to osteoarthritis, predisposing patients to progression. Low intake and low serum levels of vitamin D each appear to be associated with an increased risk for progression of osteoarthritis of the knee.
2. Positive association between serum 25-hydroxyvitamin D level and bone density in osteoarthritis
   We observed a significant positive association between serum 25(OH)D and BMD in individuals with primary knee OA, independent of sex, age, BMI, knee pain, physical activity, and disease severity. Given the high prevalence of low 25(OH)D status in persons with knee OA and the positive association between 25(OH)D and BMD, vitamin D supplementation may enhance BMD in individuals with OA.
3. Considerations in the treatment of early osteoarthritis
   Osteoarthritis is the most common form of arthritis and it is one of the leading causes of disability in all elderly populations. It results in enormous societal burden, including the need for joint replacement at an annual cost to the community of billions of dollars. Two factors that predicate the formulation of a treatment strategy for an individual with “early” osteoarthritis include the risk for toxicity from long duration of exposure to pharmaceuticals and the desirability of a treatment with the potential to reduce the rate of disease progression. These considerations favor approaches that avoid or minimize chronic pharmaceutical use in favor of safer interventions, especially ones where current evidence suggests the potential of a disease-modification effect. These should include socio-behavioral interventions that promote weight optimization and exercise, consideration of orthotics, general dietary recommendations to increase vitamin D and C intake, and an emphasis towards topical or intermittent use of pharmaceutical agents rather than long term nonsteroidal anti-inflammatory drug use.
4. Epidemiology of disease risks in relation to vitamin D insufficiency
   There is reasonably strong ecologic and case-control evidence that vitamin D reduces the risk of autoimmune diseases including such as multiple sclerosis and type 1 diabetes mellitus, and weaker evidence for rheumatoid arthritis, osteoarthritis, type 2 diabetes mellitus, hypertension and stroke.
5. Osteoporosis and vitamin-D deficiency among postmenopausal women with osteoarthritis undergoing total hip arthroplasty
   A substantial portion of these sixty-eight white women with osteoarthritis of the hip had occult osteoporosis and hypovitaminosis D. Vitamin-D deficiency was not restricted to the group with low bone density. These results support the need to consider the presence of both osteoporosis and vitamin-D deficiency in women with advanced osteoarthritis.
6. Serum vitamin D levels and incident changes of radiographic hip osteoarthritis: a longitudinal study. Study of Osteoporotic Fractures Research Group
   Low serum levels of 25-vitamin D may be associated with incident changes of radiographic hip OA characterized by joint space narrowing.
7. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety
   For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.
8. Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards
   The tolerable upper intake level (UL) for vitamin D is 50 mcg/d (2000 iu/d) in North America and in Europe. In the United Kingdom a guidance level exists for vitamin D, 25 mcg/d (1000 iu/d), defined as the dose “of vitamins and minerals that potentially susceptible individuals could take daily on a life-long basis, without medical supervision in reasonable safety.” Exposure of skin to sunshine can safely provide an adult with vitamin D in an amount equivalent to an oral dose of 250 mcg/d. The incremental consumption of 1 mcg/d of vitamin D3 raises serum 25-hydroxyvitamin D [25(OH)D ] by approximately 1 nmol/L (0.4 microg/L). Published reports suggest toxicity may occur with 25(OH)D concentrations beyond 500 nmol/L (200 microg/L). Older adults are advised to maintain serum 25(OH)D concentrations >75 nmol/L. The preceding numbers indicate that vitamin D3 intake at the UL raises 25(OH)D by approximately 50 nmol/L and that this may be more desirable than harmful. The past decade has produced separate North American, European, and U.K. reports that address UL or guidance-level values for vitamin D. Despite similar well-defined models for risk assessment, each report has failed to adapt its message to new evidence of no adverse effects at higher doses. Inappropriately low UL values, or guidance values, for vitamin D have hindered objective clinical research on vitamin D nutrition, they have hindered our understanding of its role in disease prevention, and restricted the amount of vitamin D in multivitamins and foods to doses too low to benefit public health.
9. Risk assessment for vitamin D
   The objective of this review was to apply the risk assessment methodology used by the Food and Nutrition Board (FNB) to derive a revised safe Tolerable Upper Intake Level (UL) for vitamin D. New data continue to emerge regarding the health benefits of vitamin D beyond its role in bone. The intakes associated with those benefits suggest a need for levels of supplementation, food fortification, or both that are higher than current levels. A prevailing concern exists, however, regarding the potential for toxicity related to excessive vitamin D intakes. The UL established by the FNB for vitamin D (50 microg, or 2000 IU) is not based on current evidence and is viewed by many as being too restrictive, thus curtailing research, commercial development, and optimization of nutritional policy. Human clinical trial data published subsequent to the establishment of the FNB vitamin D UL published in 1997 support a significantly higher UL. We present a risk assessment based on relevant, well-designed human clinical trials of vitamin D. Collectively, the absence of toxicity in trials conducted in healthy adults that used vitamin D dose > or = 250 microg/d (10,000 IU vitamin D3) supports the confident selection of this value as the UL.

Referenties Multi vitamine

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1. Vitamins and arthritis. The roles of vitamins A, C, D, and E.
   There are at least four mechanisms whereby the nutrient vitamins A, C, D, and E may be related to the processes that impede or give rise to OA. These nutrient vitamins have major roles in modulating oxidative stress, participating in immune responses, and contributing to cell differentiation. There is a substantial need to understand the contribution of these nutrients to OA, because they may provide important insight into ameliorating the initiation and progression of the disease. Simultaneously, greater understanding will add rationality to an area of potential intervention that is often based on anecdote. Investigation will be complex; there is the need to select appropriate systems. Typical animal model systems used in the study of OA are inappropriate because most animals can synthesize ascorbic acid. There is the need to disaggregate, as much as possible, the numerous subsets of OA and the plethora of processes that contribute to that heterogeneity. Certainly, there is the need to recognize the interdependency of the actions of each of these nutrients at the cellular level. Furthermore, humans rarely consume these nutrients as independent products. For example, watermelon is a primary source of both ascorbic acid and beta-carotene. Failure to address these complexities denies the scientist the opportunity to advance our understanding of health and disease processes. More importantly, failure to address these complexities denies the person with OA the opportunity to address his or her own health.
2. Nutraceutical therapies for degenerative joint diseases: a critical review
   
   There is growing recognition of the importance of nutritional factors in the maintenance of bone and joint health, and that nutritional imbalance combined with endocrine abnormalities may be involved in the pathogenesis of osteoarthritis (OA) and osteochondritis dissecans (OCD). Despite this, dietary programs have played a secondary role in the management of these connective tissue disorders. Articular cartilage is critically dependent upon the regular provision of nutrients (glucose and amino acids), vitamins (particularly vitamin C), and essential trace elements (zinc, magnesium, and copper). Therefore, dietary supplementation programs and nutraceuticals used in conjunction with non-steroidal, anti-inflammatory drugs (NSAIDs) may offer significant benefits to patients with joint disorders, such as OA and OCD. This article examines the available clinical evidence for the efficacy of nutraceuticals, antioxidant vitamin C, polyphenols, essential fatty acids, and mineral cofactors in the treatment of OA and related joint disorders in humans and veterinary species. This article also attempts to clarify the current state of knowledge. It also highlights the need for additional targeted research to elucidate the changes in nutritional status and potential alterations to the expression of plasma membrane transport systems in synovial structures in pathophysiological states, so that current therapy and future treatments may be better focused.
3. Low vitamin K status is associated with osteoarthritis in the hand and knee
   These observational data support the hypothesis of an association between low plasma levels of vitamin K and increased prevalence of OA manifestations in the hand and knee.
4. Nutrition: risk factors for osteoarthritis
   
   Questions about the role of diet in the prevention and treatment of their joint disorder may be among the most frequent posed by patients with osteoarthritis (OA). Interestingly, while there are thousands of lay publications recommending various arthritis diets, physicians have little information to offer based on scientific studies. Arguably, in no other aspect of rheumatology is public and medical interest so discrepant. Indeed, the traditional medical approach has been to counsel patients that, other than diets promoting weight loss, scientific research has produced no evidence to suggest that any particular nutritional intervention might be helpful for OA. In fact, studies do suggest pathways through which nutritional factors might influence the natural history of OA.
5. Vitamin intakes from supplements and fortified food in German children and adolescents: results from the DONALD study
   
   Frequent consumption of supplements is a common behavior in adults, as well as children and adolescents. We report on vitamin intake from consuming supplements, taking into account the vitamin intake from fortified and usual foods. A total of 5990 3-d weighed dietary records from 931 German subjects (452 males, 479 females, 2-18 y of age) between 1986 and 2003 from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study were evaluated. We identified 133 different vitamin-containing supplements in 451 records (7.5%). Slightly more males (8.0%) than females (7.1%) consumed supplements, with highest frequencies found between ages 15 and 18 y. For the majority (10 of 13) of vitamins (vitamin A, vitamin E, vitamin K, thiamin, riboflavin, vitamin B-6, vitamin B-12, niacin, biotin, and vitamin C), intake from usual and fortified food already reached or exceeded 80% of the recommended dietary allowances in all age groups. In the case of folate and pantothenic acid, intake from supplements was necessary to achieve at least 80% of recommended dietary allowances for half of the age groups, especially in females. Supplements with vitamin D considerably helped increase vitamin intake but failed to achieve 80% of references in almost all age groups. Intakes of vitamin A and folic acid exceeded the tolerable upper level most frequently in many age groups and were most pronounced in up to 32% and 13% of children aged 2-3 y. Intake of vitamin D, vitamin E, and vitamin C exceeded the tolerable upper level in single age groups only (<7% of subjects). For the other vitamins, no exceeded limits were identified. The ubiquitous availability of supplements might indicate that even healthy children and adolescents profit by taking them. However, it is difficult to evaluate whether consumers receive more benefits or risks from the unrestricted consumption of supplements as they are marketed today.
6. Epidemiology of disease risks in relation to vitamin D insufficiency
   There is reasonably strong ecologic and case-control evidence that vitamin D reduces the risk of autoimmune diseases including such as multiple sclerosis and type 1 diabetes mellitus, and weaker evidence for rheumatoid arthritis, osteoarthritis, type 2 diabetes mellitus, hypertension and stroke.
7. Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial
   The results provide preliminary evidence that vitamin E may exert a small but significant analgesic activity independent of a peripheral anti-inflammatory effect, but which complements standard anti-inflammatory treatment.
8. The effect of nutritional supplements on osteoarthritis
   
   Osteoarthritis (OA) is the most common form of joint disease and cause of musculoskeletal disability in the elderly. Conventional management of OA primarily focuses on the relief of symptoms, using agents such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). These drugs, however, are associated with significant side effects and fail to slow the progression of OA. Several nutritional supplements have been shown to be at least as effective as NSAIDs at relieving the symptoms of OA, and preliminary evidence suggests several of these supplements may have a role in influencing the course of OA. The purpose of this article is to review the available literature on the effectiveness and safety of nutritional supplements for the treatment of OA.

Referenties antioxidanten

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1. Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders
   The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-alpha (TNFalpha) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of beta-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include the n-3 compounds, some of which are precursors of eicosanoid synthesis, and the n-6 group which can increase formation of the pro-inflammatory cytokines TNFalpha and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so that n-3 PUFA often oppose the inflammatory effects of some n-6-PUFA. gamma-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich in n-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.
2. Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis: oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function
   Oxidative stress leads to increased risk for osteoarthritis (OA) but the precise mechanism remains unclear. Our findings clearly show that the presence of oxidative stress induces telomere genomic instability, replicative senescence and dysfunction of chondrocytes in OA cartilage, suggesting that oxidative stress, leading to chondrocyte senescence and cartilage ageing, might be responsible for the development of OA. New efforts to prevent the development and progression of OA may include strategies and interventions aimed at reducing oxidative damage in articular cartilage.
3. Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?
   Cumulative damage to tissues, mediated by reactive oxygen species, has been implicated as a pathway that leads to many of the degenerative changes associated with aging. High intake of antioxidant micronutrients, especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with OA. We found no effect of antioxidant nutrients on incident OA. These preliminary findings warrant confirmation.
4. Epidemiology of risk factors for osteoarthritis: systemic factors
   Osteoarthritis (OA) appears to be a mechanically driven but chemically mediated disease process in which there is attempted (or aberrant) repair. Well established risk factors for OA include aging, obesity, gender, and, in selected subgroups, congenital anomalies. This review addresses less well established risk factors for OA that can impact joints through their effect on systemic metabolism rather than their contribution to local joint geometry and structure. These systemic risk factors include obesity; bone and bone density; nutrients, particularly those that function as antioxidants; and genetic factors. There is great opportunity for new prevention and intervention strategies as we expand our understanding of the role of these systemic risk factors.
5. The role of nitric oxide in articular cartilage breakdown in osteoarthritis
   It is increasingly appreciated that mediators typically associated with inflammatory arthritis, such as catabolic cytokines and nitric oxide, are produced by synovium and cartilage in osteoarthritis. The role that such mediators play in the progression of cartilage degradation in osteoarthritis is under intensive investigation. Nitric oxide is a highly reactive, cytotoxic free radical that has been implicated in tissue injury in a variety of diseases. Cartilage obtained from patients with osteoarthritis produces significant amounts of nitric oxide ex vivo, even in the absence of added stimuli such as interleukin-1 or lipopolysaccharide. In vitro, nitric oxide exerts detrimental effects on chondrocyte functions, including the inhibition of collagen and proteoglycan synthesis, enhanced apoptosis, and an inhibition of B1 integrin-dependent adhesion to the extra-cellular matrix. This paper reviews recent observations regarding the role of nitric oxide in osteoarthritis and presents evidence suggesting that the inhibition of nitric oxide production could be a desirable future therapeutic strategy.
6. Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis
   Osteoarthritis and rheumatoid arthritis are characterized by focal loss of cartilage due to an up-regulation of catabolic pathways, induced mainly by pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha). In conclusion, our results suggest that nitric oxide may play a major role in altering chondrocyte functions in osteoarthritis, whereas the harmful effects of radical oxygen species are more evident in chondrocytes from patients with rheumatoid arthritis, due to an oxidant/antioxidant imbalance.
7. Peculiarities of free radical and antioxidant statute in patients with systemic lupus erythematosus and rheumatoid arthritis
   
   The state of lipid peroxidation and antioxidant defence was investigated in sera of 66 patients with rheumatoid arthritis (RA), 50 patients with systemic lupus erythematosus (SLE) and in 235 healthy donors using the method of chemiluminescence and EPR-spectroscopy. The results indicate involvement of free radical oxidation in pathogenesis of RA and SLE. Peroxide and antioxidant imbalance was more pronounced in RA than in SLE.
8. Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis
   
   Our results demonstrated that levels of LPO are increased in patients with RA compared to patients with OA. In addition, plasma TAC levels are decreased in RA due to its inflammatory character. We conclude that detecting plasma TAC levels with this novel method may be used as a routine and rapid test to verify the levels of oxidative stress in RA. Furthermore, correlating TAC and LPO levels with acute phase reactants such as ESR may give some clues about disease activity in RA.
9. Extracellular superoxide dismutase and oxidant damage in osteoarthritis
   
   EC-SOD, the major scavenger of reactive oxygen species in extracellular spaces, is decreased in humans with OA and in an animal model of OA. Our findings suggest that inadequate control of reactive oxygen species plays a role in the pathophysiology of OA.

Referenties Cayenne Peper (Capsaicine)

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1. Capsaicin: identification, nomenclature, and pharmacotherapy
   Capsaicin as a pure white crystalline material, however, acts specifically by depleting stores of substance P from sensory neurons, and has been successful in the treatment of several painful conditions (e.g., rheumatoid arthritis, osteoarthritis, peripheral neuropathies.
2. Treatment of arthritis with topical capsaicin: a double-blind trial
   It is concluded that capsaicin cream is a safe and effective treatment for arthritis.
3. Topical capsaicin in painful diabetic neuropathy. Controlled study with long-term follow-up
   Results from this preliminary study suggest that topical 0.075% capsaicin may be of value in subjects with diabetic neuropathy and intractable pain.
4. Topical capsaicin in painful diabetic neuropathy. Effect on sensory function
   Although our results and those of others show no adverse effects of topical 0.075% capsaicin on human sensory function, even in subjects with preexisting neuropathic sensory impairment, the small number of subjects tested does not justify an inferential statement on safety. Further studies in more subjects are warranted to ensure the long-term safety of capsaicin for pain relief in humans.
5. A highly successful and novel model for treatment of chronic painful diabetic peripheral neuropathy
   This study presents a new rationale and hypothesis for the successful treatment of chronic painful diabetic peripheral neuropathy. It uniquely bases the treatment algorithm on the types and sources of the pain.

Referenties D-phenylalanine

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1. DL-phenylalanine markedly potentiates opiate analgesia – an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system
   In the author’s clinical experience, concurrent treatment with DL-phenylalanine (DLPA) often appears to potentiate pain relief and also ease depression in patients receiving opiates for chronic non-malignant pain.
2. D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: implications for some important therapeutic application
   D-phenylalanine has proven to be beneficial in many human patients with chronic, intractable pain. It is proposed the enkephalinase inhibitors may be effective in a number of human “endorphin deficiency diseases” such as depression, schizophrenia, convulsive disorders and arthritis.
3. Curing trial of complicated oncologic pain by D-phenylalanine (author’s transl)]
   Our data point out the consequences the enkephalinases inhibitors will take up for the cure of intractable cancer pain.
4. Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (first report)–effect on pain threshold and inhibition by naloxone
   These findings show that DPA enhances the analgesic effect of acupuncture by the “endorphin mechanism.”
5. Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (2nd report)–schedule of administration and clinical effects in low back pain and tooth extraction
   The above findings show that DPA has an enhancing effect on acupuncture analgesia and anesthesia in clinical practice.

Referenties glucosaminoglucaan injecties

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1. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action
   
   Although the predominant mechanism of intra-articular hyaluronan (hyaluronic acid) (HA) and hylans for the treatment of pain associated with knee osteoarthritis (OA) is unknown, in vivo, in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. HA can reduce nerve impulses and nerve sensitivity associated with the pain of OA. In experimental OA, this glycosaminoglycan has protective effects on cartilage, which may be mediated by its molecular and cellular effects observed in vitro. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the production and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. Many of the physiological effects of exogenous HA may be a function of its molecular weight. Several physiological effects probably contribute to the mechanisms by which HA and hylans exert their clinical effects in knee OA.
2. Preliminary results of integrated therapy for patients with knee osteoarthritis
   
   Group III received isokinetic exercise, pulse ultrasound, and intraarticular hyaluronan therapy; Groups II and III showed significant improvements in range of motion and ambulation speed after treatment. Group III also showed the greatest increase in walking speed and decrease in disability after treatment and at followup.
3. Clinical effects of intraarticular injection of high molecular weight hyaluronan (Orthovisc) in osteoarthritis of the knee: a randomized, controlled, multicenter trial
   Our findings indicate that HMW hyaluronan is safe and seems to be effective in the treatment of mild to severe OA of the knee.
4. Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (first report)–effect on pain threshold and inhibition by naloxone
   These findings show that DPA enhances the analgesic effect of acupuncture by the “endorphin mechanism.”
5. A prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intraarticular hyaluronic acid for osteoarthritis of the knee
   Intraarticular HA was superior to placebo in improving knee pain and function, with no difference between 3 or 6 consecutive injections for the primary efficacy assessment.
6. Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group
   The results indicate that sodium hyaluronate treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee osteoarthritis in whom pain in the contralateral knee is relatively modest.
7. Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee
   NASHA was not superior to placebo for the primary efficacy analysis. However, these data may be confounded by the inclusion of patients with OA at other sites, as significant benefits over placebo were found among patients with OA confined to the knee. Future trials of OA that examine a local therapy might need to consider restricting the study population to those patients having OA of only the signal joint.
8. Clinical effects of intraarticular injection of high molecular weight hyaluronan (Orthovisc) in osteoarthritis of the knee: a randomized, controlled, multicenter trial
   Our findings indicate that HMW hyaluronan is safe and seems to be effective in the treatment of mild to severe OA of the knee
9. Efficacy of intraarticular hyaluronic acid in patients with osteoarthritis–a prospective clinical trial
   This controlled prospective clinical trial confirmed that 5 weekly intraarticular injections of HA (Hyalart) in patients with OA of the knee provide pain relief and functional improvements.
10. Viscosupplementation for the treatment of osteoarthritis of the knee
    Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period.
11. Longterm effects of intraarticular hyaluronan on synovial fluid in osteoarthritis of the knee
    This open-label study showed a statistically significant change from baseline in both SF HA concentration and complex shear modulus at 3 months following IA Hylan GF-20 injection among subjects with mild to moderate knee OA. These results suggest that one possible mechanism of action of viscosupplementation is to promote endogenous HA production. Longer-term studies are required to identify whether these changes in SF measures are important for modification of disease progression in knee OA.

Referenties Apocynin (acetovanillone)

1. Apocynin, a plant-derived, cartilage-saving drug, might be useful in the treatment of rheumatoid arthritis
   
   OBJECTIVE: To investigate whether apocynin, 1-(4-hydroxy-3-methoxyphenyl)ethanone, is able to diminish inflammation-induced cartilage destruction in rheumatoid arthritis (RA), studied in a human in vitro model. METHODS: Apocynin was added to cultures of RA peripheral blood mononuclear cells (PBMNC). Cartilage-destructive activity was determined by addition of culture supernatant to tissue samples of human articular cartilage. In addition, the proliferation of PBMNC, their production of tumour necrosis factor alpha (TN-Falpha), interleukin (IL)-1 and IL-10, and T-cell production of interferon gamma (IFN-gamma) and IL-4, as measures for T1 and T2 cell activity, were determined. RESULTS: Apocynin was able to counteract RA PBMNC-induced inhibition of cartilage matrix proteoglycan synthesis, while no effect on inflammation-enhanced proteoglycan release was found. The effect was accompanied by a decrease in IL-1 and TNF-alpha production by the MNC. No effect on T-cell proliferation was found, but the production of IFN-gamma, IL-4 and T-cell-derived IL-10 was strongly diminished. Most important, apocynin did not show any direct adverse effects on chondrocyte metabolism; on the contrary, it diminished the release of proteoglycans from the cartilage matrix. CONCLUSION: Apocynin in vitro inhibits inflammation-mediated cartilage destruction without having adverse effects on cartilage. The latter may be an advantage of apocynin over many other non-steroidal anti-inflammatory drugs. Therefore, apocynin might have an added beneficial effect in protecting RA patients from joint destruction.
2. Oral administration of the NADPH-oxidase inhibitor apocynin partially restores diminished cartilage proteoglycan synthesis and reduces inflammation in mice
   
   Apocynin, an inhibitor of NADPH-oxidase, is known to partially reverse the inflammation-mediated cartilage proteoglycan synthesis in chondrocytes. More recently, it was reported that apocynin prevents cyclooxygenase (COX)-2 expression in monocytes. The present study aimed to investigate whether these in vitro features of apocynin could be confirmed in vivo. In a mouse model of zymosan-induced acute arthritis apocynin was administered orally (0, 3.2, 16 and 80 microg/ml in the drinking water) and the effects on cartilage proteoglycan synthesis were monitored. In a mouse model of zymosan-induced inflammation of the ears apocynin was administered orally (14 mg/kg/day by gavage) and the effects on ear swelling and ex vivo produced prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-stimulated blood cells were measured. In this study, ibuprofen was used as a positive control (50 mg/kg/day by gavage) and animals received vehicle as a negative control. Apocynin dose-dependently reversed the inhibition of proteoglycan synthesis in articular cartilage of the arthritic joint. A statistically significant increase in proteoglycan synthesis was found at a dose of 80 microg/ml apocynin. Apocynin did not affect the proteoglycan synthesis of the control knee joints. Apocynin significantly decreased the zymosan-induced ear swelling at 1, 2 and 4 h (hours) after zymosan injection versus the vehicle treated group at 14 mg/kg/day. The ex vivo production of PGE2 by LPS-stimulated blood cells was significantly decreased after in vivo apocynin treatment. Ibuprofen decreased ear swelling at the same time-points as apocynin and inhibited the ex vivo produced PGE2. In conclusion, the present study confirmed two important features of apocynin in vivo: (1) oral administration of apocynin can partially reverse the inflammation-induced inhibition of cartilage proteoglycan synthesis, and (2) oral administration of apocynin has COX inhibitory effects similar to the non-steroidal anti-inflammatory drug (NSAID) ibuprofen. Therefore, apocynin might be of potential use during the treatment of chronic inflammatory joint diseases like osteoarthritis or rheumatoid arthritis.
3. Antiarthritic activity of the newly developed neutrophil oxidative burst antagonist apocynin
   The plant-phenol 4-hydroxy-3-methoxyacetophenone (trivial name apocynin) is a strong inhibitor of neutrophil superoxide anion (O2-) release in vitro. In vitro the inhibitory effect of apocynin is restricted to cells with the capacity to release peroxidase and reactive oxygen species (ROS). Peroxidase deficient cells are insensitive to apocynin. In the present study the antiinflammatory activity of apocynin was tested in collagen-induced arthritis in rats. Collagen-immunized rats were treated with different doses of apocynin in the drinking water starting at the onset of joint-swelling and terminating 14 days later, at the time when joint swelling in the control group was maximal. Apocynin-treated animals had a normal plasma level of collagen-specific antibodies, but showed a significant reduction of the joint swelling. Also the plasma IL-6 level in apocynin-treated animals was substantially lower than in control animals. No flare-up of joint swelling after termination of the treatment was observed in the apocynin-treated groups.

MSM

Hieronder vindt u alle wetenschappelijke artikelen die zijn gebruikt bij het schrijven van ons stuk over het gebruik van MSM bij artrose.

1. Methylsulfonylmethane (MSM). Monograph
   
2. Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis
   Glu, MSM and their combination produced an analgesic and anti-inflammatory effect in osteoarthritis. Combination therapy showed better efficacy in reducing pain and swelling and in improving the functional ability of joints than the individual agents. All the treatments were well tolerated. The onset of analgesic and anti-inflammatory activity was found to be more rapid with the combination than with Glu. It can be concluded that the combination of MSM with Glu provides better and more rapid improvement in patients with osteoarthritis.
3. A Multicentered, Open-Label Trial on the Safety and Efficacy of Methylsulfonylmethane in the Treatment of Seasonal Allergic Rhinitis
   The results of this study suggest that MSM supplementation of 2600 mg/day for 30 days may be efficacious in the reduction of symptoms associated with SAR. Furthermore, few side effects are associated with the use of this compound. Recent acute and subacute chronic toxicologic data on the same source of MSM as used in this study, further validate the safety of this product
4. Toxicity of methylsulfonylmethane in rats
   It is concluded that MSM is well tolerated in rats at an acute dose of 2 g/kg and at a subacute chronic dose of 1.5 g/kg.
5. Sulfur in human nutrition and applications in medicine
   1 MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders. Other sulfur compounds such as SAMe, dimethylsulfoxide (DMSO), taurine, glucosamine or chondroitin sulfate, and reduced glutathione may also have clinical applications in the treatment of a number of conditions such as depression, fibromyalgia, arthritis, interstitial cystitis, athletic injuries, congestive heart failure, diabetes, cancer, and AIDS.
6. Aspirin and methylsulfonylmethane (MSM): a search for common mechanisms, with implications for cancer prevention
   These experiments indicated that aspirin and MSM induced differentiation by a COX-independent mechanism(s) and suggested that a common mechanism for the chemopreventive action invoked by both agents might be the activation of gene functions leading to differentiation and thereby dismantling the cellular capacity for proliferation.
7. DMSO and MSM The Biochemical Oxygen Transport Pair A new insight into their biochemistry that explains the claims for their wide-ranging health and energy benefits
   
   DMSO is a widely used commercial solvent derived from trees (living plants) as a byproduct from the production of paper. There are so many claimed health benefits from its use, one has to wonder if it doesn’t perform a similar vital function in the biochemistry of plants.
8. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial
   MSM (3g twice a day) improved symptoms of pain and physical function during the short intervention without major adverse events. The benefits and safety of MSM in managing OA and long-term use cannot be confirmed from this pilot trial, but its potential clinical application is examined. Underlying mechanisms of action and need for further investigation of MSM are discussed.
9. Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis
   Glu, MSM and their combination produced an analgesic and anti-inflammatory effect in osteoarthritis. Combination therapy showed better efficacy in reducing pain and swelling and in improving the functional ability of joints than the individual agents. All the treatments were well tolerated. The onset of analgesic and anti-inflammatory activity was found to be more rapid with the combination than with Glu. It can be concluded that the combination of MSM with Glu provides better and more rapid improvement in patients with osteoarthritis.
10. Oral developmental toxicity study of methylsulfonylmethane in rats
    Therefore, under the conditions of this study, the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity was 1000 mg/kg/day.
11. Toxicity of methylsulfonylmethane in rats
    It is concluded that MSM is well tolerated in rats at an acute dose of 2 g/kg and at a subacute chronic dose of 1.5 g/kg.