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Table 1 Summary of Studies providing overview of the treatment options for knee osteoarthritis

From: Osteoarthritis- a systematic review of long-term safety implications for osteoarthritis of the knee

Treatment option Level of evidence (type of trial) Reference Study population characteristic Intervention Outcome measure Medium-long term impact on the disease Non-disease side effects (with potential to last 12 months)
Lifestyle
Exercise
  II (RCT) Messier et al. (2004) [8] 252 patients older than 60 with BMI > 28 Exercise and diet, diet only, exercise only WOMAC Positive 1 patient tripped with laceration to forehead
II (RCT) Nejati, et al. (2015) [9] 56 patients with grade 2–4 Kellgren-Lawrence (KL) Stretching and leg exercises VAS and KOOS Positive Nil
II (RCT) Jenkinson et al. (2009) [10] 389 patients older than 45 with BMI > 28 Diet and exercise, diet only, exercise only WOMAC Positive Nil
II (RCT) Kawasaki et al. (2008) [11] 142 female patients with moderate knee-OA Exercise with or without glucosamine or risendronate WOMAC Neutral Nil
Weight reduction
  III(Prospective Cohort) Gersing et al. (2017) [12] 640 patients Weight loss > 10% or 5–10% MRI WORMS Positive Nil
Pharmacological
Glucosamine and Chondroitin sulphate (CS)
  II (RCT) Pavelká et al. (2002) [13] 202 patients aged 45–70 Glucosamine 1500 mg daily for 3 years WOMAC Positive Gastrointestinal side effects
II (RCT) Reginster et al. (2001) [14] 212 patients Glucosamine 1500 mg daily for 3 years WOMAC Positive Gastrointestinal side effects
II (RCT) Sawitzke et al. (2008) [15] 572 patients with KL grade 2–3 Glucosamine or chondroitin JSW Neutral Gastrointestinal side effects
Paracetamol
  II (RCT) Temple et al. (2006) [16] 571 patients with knee or hip OA Paracetamol or Naproxen for 6 or 12 months WOMAC Positive Hepatic, renal and gastrointestinal side effects
Non-steroidal anti-inflammatory drugs (NSAIDs)
  II (RCT) Temple et al. (2006) [16] 571 patients with knee or hip OA Paracetamol or Naproxen for 6 or 12 months WOMAC Positive Hepatic, renal and gastrointestinal side effects
II (RCT) Sawitzke et al. (2010) [17] 662 patients with KL grade 2–3 Celecoxib 2oomg for 2 years WOMAC Neutral Gastrointestinal side effects
Injectables
Intra-articular (IA) corticosteroids
  II (RCT) McAlindon et al. (2017) [18] 140 patients with KL grade 2–3 Triamcinolone 3 monthly for 2 years MRI cartilage loss Negative Facial flushing, injection site pain
II (RCT) Raynauld et al. (2003) [19] 68 patients with KL grade 2–3 Triamcinolone 3 monthly for 2 years WOMAC Positive Nil
Intra-articular hyaluronic acid (IAHA)
  III (Prospective cohort) Benazzo et al. 2016) [20] 50 patients, older than 40 2 x Hymovis 3 ml a week apart, then again at 6 months WOMAC, JSW Positive Increase in knee pain, HA, flu like symptoms, back pain
III (Prospective cohort) Conrozier et al. (2003) [21] 155 patients 3 x intraarticular Hylan GF-20 a week apart Patient satisfaction and safety Neutral Nil
III (Prospective cohort) Huskin et al. (2008) [22] 62 patients KL grade 1–2 3 x intraarticular Hylan GF-20 a week apart WOMAC Positive Pain, swelling and synovitis
II (RCT) Jorgensen et al. (2010) [23] 337 patients Intra-articular Hyaluron weekly for 5 weeks LFI, pain on VAS walking > 50 m Neutral  
II (RCT) Juni et al. (2007) [24] 660 patients 3 intra-articular injections of 3 different HAs WOMAC Neutral Pain, swelling and synovitis
II (RCT) Navarro-Sarabia et al. (2011) [25] 306 patients KL grade 2–3 5 intra-articular injections at 6 month intervals OARSI responder criteria Positive Pain, swelling, rash and bleeding
II (RCT) Ozturk et al. (2006) [26] 24 patients 3 injections as week apart and then repeat at 6 months with or without triamcinolone WOMAC Positive  
II (RCT) Vaquerizo et al. (2013) [27] 96 patients 3 x PRGF-Endoret or 1 x Durolane WOMAC Positive  
III (Prospective cohort) Kearey et al. (2017) [28] 119 patients Single intra-articular injection of 6-mL hylan G-F WOMAC Positive  
III (Prospective case) Yan et al. (2015) [29] 110 knees from 95 patients Single intra-articular injection of 6-mL hylan G-F Pain VAS and Likert scales Positive Self-limiting pain and swelling over injection site
Platelet Rich Plasma (PRP)
  II(RCT) Filardo et al. (2012) [30] 144 patients 3 injections of single or double spinning PRP IKDC, EQ-VAS and Tegner scores Positive Swelling and pain over injection site
II (RCT) Smith (2016) [31] 30 patients 3 weekly leucocyte poor PRP WOMAC Positive Nil
Stem Cells
  III (Prospective case) Emadedin et al. (2012) [32] 6 patients Bone marrow MSCs MRI cartilage mapping Positive Nil
III (Prospective case) Emadedin et al. (2015) [33] 18 patients Bone marrow MSCs WOMAC Positive Rash and erythema
III (Prospective case) Orozco et al. (2013) [34] 12 patients Bone marrow MSCs MRI cartilage mapping Positive Nil
II (RCT) Vega et al. (2015) [35] 30 patients Allogenic bone marrow MSCs vs IAHA MRI cartilage mapping Positive Transient joint pain and swelling
III (Prospective case) Fodor and Paulseth (2016) [36] 8 knees in 6 patients KL grade 1–3 Adipose derived SVF cells WOMAC Positive Nil
Surgical
Arthroscopy
  III (Prospective cohort) Rongen et al. (2017) [37] 4674 patients with 335 meniscectomies Arthroscopic meniscectomy Progression to TKA Negative Nil
Total Knee Arthroplasty (TKA)
  III (Prospective cohort) Brophy et al. (2014) [38] 1268 patients Previous knee surgery Progression to TKA Neutral Nil
III (Prospective cohort) El-Galaly et al. (2017) [39] 1421 patients Post-traumatic fracture TKA Failure of implant Neutral Nil
II(RCT) Skou et al. (2015) [40] 95 patients with moderate to severe OA TKA KOOS Positive Major medical side effects
III(Matched Cohort) Ansari et al. (2017) [41] 21 patients with KOA having previous micro fracture TKA KSS score Positive 1 x arthrofibrosis