<h2>Practice points</h2><ul><li>Glucosamine and chondroitin are natural building blocks of cartilage and may improve osteoarthritis (OA) pain and function over time (weeks-months) and slow progression of disease </li><li>Curcumin and boswellia have anti-inflammatory properties and may improve clinical symptoms. A 30% enriched boswellia extract showed significant benefit within 7 days, with significant improvement in pain and functionality after 90 days of treatment </li><li>Anti-inflammatory agents such as green-lipped mussel extract (PCSO-524™) and fish oil (&gt;2.7grams) may improve clinical symptoms</li><li>Vitamin D - low levels are associated with OA progression and severity. Ensure adequate serum vitamin D and consider supplementation if insufficient</li></ul><ul><li> <ul><li> <h2>Description</h2> </li><li>OA is the most common joint disorder in the world.1 In Western countries it is one of the most frequent causes of pain, disability and loss of function in adults. Characterised by joint pain and mobility impairment associated with the gradual wearing of cartilage.2 Inflammation is also an important factor in the development and progression of OA.3</li><li><h2>Special consideration - Vitamin D</h2></li><li> Low levels (serum 25(OH)D &lt; 25 μg/ml) are associated with OA progression.13 There is a strong association between serum levels and cartilage loss.14 Adequate levels are associated with less pain in knee OA.15 </li></ul> </li></ul>

<h2>Management principles2</h2><ul><li>Optimise quality of life</li><li> Improve mobility and function, reduce pain and disability</li><li>Prevent or slow further progression</li><li> Optimise self-management</li><li>Prevent repeated acute episodes</li><li> Prevent or delay complications</li></ul>

Management

<h2>Primary recommendations</h2><h2>GLUCOSAMINE AND CHONDROITIN</h2>Characteristics6<ul><li>Compounds that are normal constituents of cartilage proteoglycans</li><li>Glucosamine is available as sulfate (GS) or hydrochloride (GH). More clinical research has been conducted with GS</li><li>A combination with chondroitin sulfate (CS) may be more effective</li></ul>Mechanism of action6<ul><li>Anti-inflammatory</li><li>Inhibits cartilage degradation</li></ul>ResearchA randomised controlled trial (Fransen et al 2015) investigated GS 1500 mg/d, CS 800 mg/d or both in 605 patients with painful knee OA.7 Outcomes were joint space narrowing (JSN) and clinical symptoms.The combination GS + CS group had significant reduction in JSN (0.1 mm) vs placebo which was approximately ½ of that in controls after 2 years. The authors state that ‘If this reduction in JSN were to be sustained over a clinically meaningful period of OA development (e.g.10 to 15 years), it would be very meaningful indeed’.The number needed to treat (NNT) was 14, meaning 14 people would need to be treated for 2 years to prevent one knee-replacement surgery in following 2-5 year period.Knee pain and physical function (WOMAC) improved between baseline and year 1 in all groups with no further improvements in year 1-2.A 2015 Cochrane Review found chondroitin alone, or with glucosamine resulted in statistically significant and clinically meaningful improvement in pain scores (10% lower than placebo).8 There was an 8 point improvement in WOMAC pain and a 2 point improvement in Lequesne’s Index; NNT was 5. There was a lower risk of adverse effects compared to control. Comparative informationMay give similar pain relief to NSAIDs and paracetamol. Slower to work but better tolerated. <ul><li>Non-inferiority trial comparing 200 mg/d celecoxib with 1500 mg GH+1200 mg CS found equal pain reduction (~50%)9</li><li>GS may be comparable to NSAIDs and paracetamol for symptom relief but onset of action is slower (4-8 weeks up to 6 months)10</li><li>GS 1500 mg/d is tolerated at least as well as ibuprofen 1200 mg per day, and is better tolerated than piroxicam 20 mg/d10</li><li> CS may be as effective as NSAIDs for symptom relief but has slower onset of action (2-4 months)6</li></ul>Dosage<ul><li>GS 1500 mg/day6</li><li>CS 800-1200 mg/day6</li></ul>Adverse effects<ul><li>GS may cause mild gastrointestinal (GI) problems -nausea, heartburn, diarrhoea, constipation10</li><li>Adverse effects to GS and CS are generally comparable to placebo10,11</li><li>Key interactions</li><li><ul><li>Anticoagulant and antiplatelet agents: both CS and glucosamine may have additive effect to the drug. Case report evidence for both shows possible interaction with moderate-high severity of outcome. Avoid concomitant use6,12</li><li>Hypoglycaemic drugs: glucosamine may decrease drug effect, however, clinical trials indicate no interaction therefore interaction is unlikely, but use with caution under supervision of HCP6,12</li></ul></li><li><h2>CURCUMIN AND BOSWELLIA</h2></li><li> Mechanism of action6 <ul><li>Curcumin: the active constituent of Curcumin longa has a multi-faceted mode of action including selectively inhibiting the inflammatory enzyme cyclooxygenase-2 (COX-2).19 It also inhibits leukotriene formation and regulates numerous transcription factors, cytokines, protein kinases, adhesion molecules and redox status linked to inflammation20</li><li>Boswellia serrata: mainly inhibits inflammatory mediator 5-lipoxygenase (5-LOX). It also inhibits cytokines and tumour necrosis factor alpha (TNF)-α.21 The boswellic acids, of which AKBA is the most active component, are considered the main constituents responsible for the anti-inflammatory effects of boswellia22</li></ul> Research <ul><li>In two clinical trials using the boswellia 30%-enriched AKBA extract, patients with OA of the knee began to show significant benefit within 7 days of treatment, with significantly improved pain and functionality scores after 90 days of treatment22</li><li>A clinical evaluation of a formulation containing both curcumin and boswellia extracts used in the management of knee OA, found efficacy and tolerability of the formulation to be superior to those of celecoxib (NSAID)23</li></ul> Dosage <ul><li>500 mg turmeric tablets, containing 100 mg curcumin twice daily (Meriva extract)19</li><li>100 mg or 250 mg daily specific boswellia extract (5-Loxin)24</li></ul> Adverse effects <ul><li>Curcumin: generally well tolerated. The most common side effects are gastrointestinal and include constipation, dyspepsia and diarrhoea19</li><li>Boswellia: usually well tolerated. Some reported side effects include diarrhoea, nausea, abdominal pain, heartburn, oedema and general weakness19</li><li>Key interactions</li><li>Curcumin</li><li><ul><li>CYP450 enzyme substrates: may increase or decrease drug effect, effect variable (dependent on drug or disease). Use with caution under supervision of an HCP and monitor12</li><li>Hypoglycaemic drugs: may have additive hypoglycaemic effect, likelihood is possible. Use with caution under supervision of an HCP and monitor12</li><li>Sulfasalazine: may increase drug blood levels, likelihood is possible and severity moderate to high. Avoid concomitant use12</li><li>Anticoagulants and antiplatelet agents: may increase drug effect, likelihood is theoretical and severity moderate to high. Use with caution under supervision of an HCP and monitor12</li></ul></li><li>Boswellia</li><li><ul><li>CYP450 enzyme substrates: may increase or decrease drug effect, likelihood is theoretical and severity variable (dependent on drug or disease). Use with caution under supervision of an HCP and monitor12</li><li>Immunosuppressants: may have an opposing effect on the drug, likelihood is theoretical and severity variable (dependent on drug or disease). Use with caution under supervision of an HCP and monitor12</li></ul></li></ul> </li></ul> For more information on key interactions visit: <a href="~/link.aspx?_id=4471DACF65C148EA8FD82B23FD6712D4&_z=z">https://www.blackmoresinstitute.org/interactions</a>

Primary

<h2>Secondary recommendations</h2><h2>GREEN-LIPPED MUSSEL EXTRACT (PCSO-524™)</h2><ul><li> Mechanism of action6 <ul><li>Inhibition of inflammatory leukotrienes and possibly some prostaglandins18 </li></ul> Research <ul><li>In a 24-week study 80 OA patients received either green-lipped mussel extract (PCSO-524™) or placebo, participants were allowed paracetamol as a rescue treatment and were measured via the visual analog scale (VAS) for pain, patient’s and physician’s assessment. There was greater improvement in the assessment of arthritis in those that took PCSO-524™ from week 4 following adjustment in paracetamol dose18</li><li>After a 4- and 8-week treatment period, 60 patients with symptomatic OA of the knee and hip received PCSO-524™ at a dose of 2 capsules twice a day, participants were measured via VAS, Lequesne functional index, as well as global assessment by patients and physician. There was significant improvement of the signs and symptoms of OA as determined by efficacy measures, 53% and 80% of patients experienced significant pain relief and improvement in joint function18</li></ul> Dosage <ul><li>100 mg twice daily17</li></ul> Adverse effects <ul><li>Well-tolerated with no serious side effects17,18</li><li>Key interactions</li><li><ul><li>Anticoagulant and antiplatelet agents: may increase drug effect, conflicting data with several case reports of raised INR, however, small human study found no effect on platelet aggregation, prothrombin time, APTT, fibrinogen or factor VII. Likelihood theoretical, severity moderate to high. Use with caution under supervision of an HCP and monitor12</li></ul></li><li><h2>FISH OIL (Omega-3 fatty acids</h2></li><li><ul><li> Mechanism of action6 <ul><li>Concentrated fish oil (EPA &gt;520mg/capsule) competitively inhibits the conversion of arachidonic acid to the pro-inflammatory eicosanoids (prostaglandins); reducing their synthesis25 </li></ul> Research <ul><li>Research suggests the dose needed to reduce joint inflammation in rheumatoid arthritis is 2.7 g of omega-3 (EPA plus DHA) daily.26 A therapeutic trial for osteoarthritis could be considered if inflammation is suspected</li></ul> Dosage <ul><li>2.7 g of omega-3 (EPA plus DHA) to reduce joint inflammation26</li></ul> Adverse effects <ul><li>Omega-3 fatty acids are very well tolerated. Up to 3 g/d </li><li>EPA+DHA is generally recognised as safe (GRAS)27</li></ul> Key interactions <ul><li>Antihypertensive drugs: may have additive hypotensive effect depending on fish oil dose. BP should be monitored when a patient is on high dose fish oil12</li><li>Anticoagulant and antiplatelet agents: high doses of fish oil (&gt;3 g/day omega-3 fatty acids) may increase the risk of bleeding with these drugs. There is conflicting data multiple clinical trials have found no increase in the risk of bleeding with antiplatelet or anticoagulant drugs, however, there are some studies that suggest an interaction, particularly at higher doses. Use with caution under the supervision of an HCP and monitor12</li><li>Chemotherapeutic agents: may decrease drug effect. Avoid concomitant use12</li></ul> </li><li> </li><li>For more information on key interactions visit: <a href="~/link.aspx?_id=4471DACF65C148EA8FD82B23FD6712D4&_z=z">https://www.blackmoresinstitute.org/interactions</a></li></ul></li></ul> </li></ul>

Secondary

<h2>Diet and lifestyle</h2><ul><li>Exercise therapy: should be tailored to individual preference. Land-based exercise including walking, resistance, stretching and strengthening; swimming or Tai Chi can relieve pain, improve function and overall aerobic fitness2</li><li>Weight loss: obesity is a risk factor for OA development and progression. Weight loss improves pain and disability2</li><li>There is preliminary data that a Mediterranean diet may be beneficial4,5</li></ul>

Diet & lifestyle

<h2>References</h2>1. Kotsirilos V, Vitetta L, Sali A. A guide to evidence-based integrative and complementary medicine. Elsevier 2011 2. RACGP 2009. Guidelines for the non-surgical management of hip and knee osteoarthritis. 3. Wang Q et al. Identification of a central role for complement in osteoarthritis. Nat Med 2011;17(12):1674-79. 4. Musumeci G et al. Extra-virgin olive oil diet and mild physical; activity prevent cartilage degeneration in osteoarthritis model: an in vivo and in vitro study on lubricin expression. J Nutr Biochem 2013;24(12):2064-75. 5. Rayman MP, Pattinson DJ. Dietary manipulation in musculoskeletal conditions. Best Pract Clin Rheumatol 2008;22(3):535-61. 6. Braun L and Cohen M. Herbs and Natural Supplements 4th ed. Elsevier 2015. 7. Fransen M et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebocontrolled clinical trial evaluating single and combination regimens. Ann Rheum Dis 2015;74(5):851-8. 8. Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ. Chondroitin for osteoarthritis. Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No.: CD005614. DOI: 10.1002/14651858. CD005614.pub2. 9. Hochberg MC et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis 2015;0:1–8. 10. Natural Medicines Database 2015. Glucosamine Sulfate monograph.11. Natural Medicines Database 2015. Chondroitin Sulfate monograph. 12. Blackmores Institute Complementary Medicines Interactions Guide 7th ed. 2015. 13. Zhang FF et al. Vitamin D defi ciency is associated with progression of knee osteoarthritis. J Nutr. 2014;144(12):2002-8. 14. Cao Y et al. Association between serum levels of 25-hydroxyvitamin D and osteoarthritis: a systematic review. Rheumatology.2013;52(7):1323-34. 15. Glover TL et al. A Cross-Sectional Examination of Vitamin D, Obesity, and Measures of Pain and Function in Middle-Aged and Older Adults with Knee Osteoarthritis. Clin J Pain 2015;31(12):1060-7. 16. Arthritis Australia 2007. Arthritis Information Sheet. Fish Oils. 17. Cho SH et al. 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 multicentre 2-month clinical trial. European Annals of allergy and clinical immunology 2003,35(6) 212-216 18. Lau CS et al. Treatment of knee osteoarthritis with Lyprinol, lipid extract of the green-lipped mussel - a double-blind placebo controlled study. Progress in Nutrition 2004;6(1) 17-31.19. Natural Medicines – Professional, Turmeric. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional. aspx?productid=662 Accessed 03/01/2018 20. Aggarwal B et al. Potential Therapeutic Effects of Curcumin, the Anti-Inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases. Int J Biochem Cell Biol. 2009; 41(1): 40–59. doi: 10.1016/j.biocel.2008.06.010 21. Appleton J. Turmeric and Frankincense in Inflammation: an Update. Nat Med Jour. Sept 2011 Vol 3 Issue 9 22. Sengupta, K et al. Comparative Efficacy and Tolerability of 5-Loxin® and Aflapin® Against Osteoarthritis of the Knee: A Double Blind, Randomized, Placebo Controlled Clinical Study. Int J Med Sci. 2010; 7(6):366-377 23. Kizhakkedath, R. Clinical evaluation of a formulation containing Curcuma longa and Boswellia serrata extracts in the management of knee osteoarthritis. 2013 Nov;8(5):1542-8 24. Natural Medicines. Boswellia monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional. aspx?productid=63 Accessed 19 February 2019 25. Hendler S, PDR for Nutritional Supplements, 2nd Ed., Fish Oil Chapter, Thompson Reuters, 2008: 208-214 26. Arthritis Australia. Fish oil. https://arthritisaustralia.com.au/managing-arthritis/living-with-arthritis/complementary-treatments-and-therapies/fish-oils/ Accessed 19 February 2019. 27. Natural Medicines. Fish oil monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=993 Accessed 19 February 2019

Osteoarthritis

Recommended for you

Acne

Stress and mild anxiety

Respiratory tract infections

Cognitive health