40. Hochberg MC, J Martel-Pelletier, J Monfort et al. on behalf of the MOB`VES Investigation Group: Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non inferiority trial versus celecoxib. Ann Rheum Dis, Published Online First, DOI: 10.1136/annrheumdis-2014–206792

41. Christensen R, Bartels EM, Astrup A et al. Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials. Osteoarthritis Cartilage 2008; 16: 399–408

42. Bartels EM, Bliddal H, Schondorff PK et al. Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials. Osteoarthritis Cartilage 2010; 18: 289–96

43. The European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC). Available from: (http://www.ema.europa.eu/ema/index.jsp?curl= pages/news _and_events/news/2013/12/ news_details_001985.jsp&mid=WC0b 01ac058004d5c1); 2013

44. Reginster JY, Badurski J, Bellamy N et al. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis; results of a double-blind, randomised placebo-controlled trial. Ann Rheum Dis 2013; 72: 179–86

45. The European Medicines Agency. European Medicines Agency recommends that Protelos/Osseor remain available, but with further restrictions. Available from: (http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_
events/ news/2014/02/news_details_
002031.jsp &mid=WC0b01ac058001d126); 2014

46. Lin J, Zhang W, Jones A et al. Efficacy of topical nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. Br Med J 2004; 329: 324–6

47. Tugwell PS, Wells GA, Shainhouse JZ. Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. J Rheumatol 2004; 31: 2002–12

48. Simon LS, Grierson LM, Naseer Z et al. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of tropical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 2009; 238–45.

49. Chou R, McDonagh MS, Nakamoto E et al. Analgesics for osteoarthritis: An update of the 2006 comparative effectiveness review [internet]. Rockville, MD: Agency for Healthcare Research and Quality (US); 2011

50. Underwood M, Ashby D, Cross P et al. TOIB study team. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study. Br Med J 2008; 336: 138–42

51. Matthews P, Derry S, Moore RA et al. Topical rubefacients for acute and chronic pain in adults. Cochrane Database Syst Rev 2009; 8:CD007403

52. Zhang W, Jonas A, Doherty M. Does paracetamol (acetaminophen) reduce the pain of osteoarthritis? A meta-analysis of randomised controlled trials. Ann Rheum Dis 2004; 63: 901–7

53. Pincus T, Koch G, Lei H et al. Patient preference for Placebo, Acetaminophe (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthrtitis. Ann Rheum Dis 2004; 63:931–9

54. Lagnaoui R, Baumevielle M, Bégaud B et al. Less use of NSAIDs in long-term than in recent chondroitin sulphate users in osteoarthritis: a pharmacy-based observational study in France. Therapie 2006; 61: 341–6

55. Bannuru RR, Natov NS, Obadan IE et al. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum 2009; 61: 1704–11

56. Abbott T, Altmann RD, Dirnef R et al. Do hyaluronic acid injections delay total knee replacement surgery? Arthritis Rheum 2013; 65: 910–1

57. Bannuru RR, Vaysbrot EE, Sullivan MC et al. Relative efficacy of hyaloronic acid in comparison with NSAIDs for knee osteoarthritis: a systematic review and meta-analysis. Semin Arthritis Rheum 2013; 43: 593–9

58. Bellamy N, Campbell J, Robinson V et al. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev 2006; CD005328

59. Cepeda MS, Camargo F, Zea C et al. Tramadol for osteoarthritis: a systematic review and metaanalysis. J Rheumatol 2007; 34: 543–55

60. Emkey R, Rosenthal N, Wu SC et al. Efficacy and safety of tramadol/ acetaminophen tablets (Ultracet) as add-on therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal anti-inflammatory drug: a multicenter, randomized, double-blind, placebo-controlled trial. J Rheumatol 2004; 31: 150–6

61. Altman RD. Pain relief in osteoarthritis: the rationale for combination therapy. J Rheumatol 2004; 31: 5–7

62. Solomon DH, Rassen JA, Glynn RJ et al. The comparative safety of analgesics in older adults with arthritis. Arch Intern Med 2010; 170: 1968–76

63. Arendt-Nielsen L, Nie H, Laursen MB et al. Sensitization in patients with painful knee osteoarthritis. Pain 2010; 149:573–81

64. Laupattarakasem W, Laopaiboon M, Laupattarakasem P et al. Arthroscopic debridement for knee osteoarthritis. Cochrane Database Syst Rev 2008; CD005118

65. Moseley JB, O’Malley K, Petersen NJ et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 2002; 347: 81–8

66. Ravaud P, Moulinier L, Giraudeau B et al. Effects of joint lavage and steroid injection in patients with osteoarthritis of the knee: results of a multicenter, randomized, controlled trial. Arthritis Rheum 1999; 42: 475–82

67. Kirkley A, Birmingham TB, Litchfield RB et al. A randomized trial of arthroscopic surgery for osteoarthritis of the knee. N Eng. J Med 2008; 359: 1097–107