Osteoarthritis

| Practice points|

• 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. They are well tolerated; may rarely cause gastrointestinal upset• Vitamin D - low levels are associated with OA progression and severity. Ensure adequate serum vitamin D and consider supplementation if insuffi cient• Anti-infl ammatory agents such as high dose fi sh oil, turmeric and green-lipped mussel extract. May improve clinical symptoms

| Description |

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 Infl ammation is also an important factor in the development and progression of OA.3

| Management principles2 |

• Optimise quality of life • Improve mobility and function, reduce pain and disability• Prevent or slow further progression• Optimise self-management • Prevent repeated acute episodes • Prevent or delay complications

| Primary recommendations |

GLUCOSAMINE AND CHONDROITIN

Characteristics6

• Compounds that are normal constituents of cartilage proteoglycans• Glucosamine is available as sulfate (GS) or hydrochloride (GH). More clinical research has been conducted with GS• A combination with chondroitin sulfate (CS) may be more effective

Mechanism of action6

• Anti-infl ammatory• Inhibits cartilage degradation

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 signifi cant 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 signifi cant 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.• Non-inferiority trial comparing 200 mg/d celecoxib with 1500 mg GH+1200 mg CS found equal pain

Complementary medicines

GLUCOSAMINE AND CHONDROITIN

MUSCULOSKELETAL

reduction (~50%)9• 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

• 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

• CS may be as effective as NSAIDs for symptom relief but has slower onset of action (2-4 months)6

Dosage• Typical dose of GS is 1500 mg/d however higher

doses may be required in people with higher BMI6

• Typical dose of CS is 800-1200 mg/d6

Adverse effectsGS may cause mild gastrointestinal (GI) problems -nausea, heartburn, diarrhoea, constipation10

Adverse effects to GS and CS are generally comparable to placebo10,11

InteractionsGlucosamine and chondroitin may increase the risk of bleeding with warfarin. Use with caution and monitor6,12

| Secondary recommendations |

VITAMIN DLow levels (serum 25(OH)D < 25 µg/ml) are associated with OA progression13

There is a strong association between serum levels and cartilage loss14

Adequate levels are associated with less pain in knee OA15

HIGH DOSE OMEGA-3 FATTY ACIDSResearch suggests the dose needed to reduce infl ammation is 2.7 g/d omega-3 (EPA plus DHA)16

TURMERICA proprietary extract of turmeric with enhanced bioavailability (Theracumin) has demonstrated anti-infl ammatory effects and improved clinical symptoms in osteoarthritis. Dose 300-600 mg/d curcumin6

GREEN-LIPPED MUSSEL EXTRACTA proprietary lipid extract of New Zealand green-lipped mussel has demonstrated anti-infl ammatory effects and may provide relief of osteoarthritic pain17,18

| Diet and lifestyle recommendations |

• 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 fi tness2

• Weight loss: obesity is a risk factor for OA development and progression. Weight loss improves pain and disability2

• There is preliminary data that a Mediterranean diet may be benefi cial4,5

REFERENCES 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. Identifi cation 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 placebo-controlled 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 effi cacy 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.

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