Knee Osteoarthritis

==Epidemiology==
The lifetime risk of total knee replacement in New Zealand has grown rapidly from 2000 to 2015. The risk for females increased from 9.4% in 2000 to 16.8% in 2015, a relative increase of 78%. Males increased from 8.1% in 2000 to 16.0% in 2015, a relative increase of 97%.
==Treatment==
===Non-Pharmacological===
Weight Loss: Weight loss is the most effective non-surgical management strategy. The pain associated with knee osteoarthritis is thought to be secondary to both local and systemic factors. Adipokines are directly involved in the inflammatory component of OA and cartilage damage. The best results are seen with combined diet plus exercise. The IDEA trial showed that exercise plus weight loss resulted in a 50% decrease in pain scores, and 38% of patients reported no or little pain at the end of the trial.Messier SP, Mihalko SL, Legault C, Miller GD, Nicklas BJ, DeVita P, Beavers DP, Hunter DJ, Lyles MF, Eckstein F, Williamson JD, Carr JJ, Guermazi A, Loeser RF. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA. 2013 Sep 25;310(12):1263-73. doi: 10.1001/jama.2013.277669. PMID: 24065013; PMCID: PMC4450354. There is a dose response curve with weight loss, and best results are seen with at least 10% weight loss. In the elderly it is important to also add strengthening exercises. There appears to be a benefit from bariatric surgery, too.
Furthermore a randomised controlled trial comparing the once weekly injectable semaglutide to placebo, showed very large reductions in pain by week 68 of the study (−41.7 points with semaglutide and −27.5 points with placebo from baseline, WOMAC scores which are a scale from 0-100 with higher numbers being worse). The weight loss was −13.7% with semaglutide and −3.2% with placebo. Hence this trial also showed that patients need to aim for at least 10% weight loss.
Undertaking knee arthroplasty in order to allow for increased exercise and therefore weight loss is not evidence based. Most patients actually gain significant weight following knee arthroplasty despite physiotherapy. It is not known how to predict those that will gain weight following surgery. Obesity should be regarded as a separate condition that will not resolve with an improvement in function.Zeni JA Jr, Snyder-Mackler L. Most patients gain weight in the 2 years after total knee arthroplasty: comparison to a healthy control group. Osteoarthritis Cartilage. 2010 Apr;18(4):510-4. doi: 10.1016/j.joca.2009.12.005. Epub 2009 Dec 21. PMID: 20060949; PMCID: PMC2846226.
Exercise Therapy: Exercise has been shown to reduce pain and improve function. It is more effect than a single glucocorticoid injection at one year. The mechanism of action is partially through anti-inflammatory effects in particular IL-6 even without weight loss. The maximal benefit at 2 months, and thereafter the effect slowly diminishes, being no better than usual care at 9 to 18 months. Potential reasons for diminishing effects are poor long-term adherence, continued weight gain, and background worsening of the problem. There are better effects in those who are younger, with milder OA and who weren’t awaiting knee replacement. Exercise doesn’t harm the cartilageGoh, S.-L., Persson, M. S., Stocks, J., Hou, Y., Lin, J., Hall, M. C., … Zhang, W. (2019). Efficacy and potential determinants of exercise therapy in knee and hip osteoarthritis: a systematic review and meta-analysis. Annals of Physical and Rehabilitation Medicine.
Manual Therapy: Mobilisation with movement improves pain, range of motion, and functionalGidey Gomera Weleslassie, Melaku Hailu Temesgen, Abayneh Alamer, Gebrerufael Solomon Tsegay, Teklehaimanot Tekle Hailemariam, Haimanot Melese, "Effectiveness of Mobilization with Movement on the Management of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials", Pain Research and Management, vol. 2021, Article ID 8815682, 12 pages, 2021. DOI
Insoles: Insoles are pProbably not effective. For medial knee OA – negative meta-analysis of 12 studies in 2013 for lateral wedge insoles when compared to a neutral insole. Publication bias was detected.Parkes MJ, Nasimah M, Lunt M, et al. Lateral wedge insoles as conservative treatment for pain in patients with medial knee osteoarthritis. A meta-analysis. JAMA 2013;310(7):722-730. For lateral knee OA – one small study showing benefit with medial wedge insoles.
===Pharmacological===
Topical Capsaicin: This works through desensitisation of nociceptive fibres. The causative role of substance P depletion has come into question. It causes local burning, improves with continued application. It is funded in New Zealand if NSAIDs contraindicated.
Topical NSAIDs: Cochrane showed 60% achieved at least 50% improvement (better than placebo), and is comparable to oral formulationsDerry  S, Conaghan  P, Da Silva  JAP, Wiffen  PJ, Moore  RA. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No.: CD007400. DOI: 10.1002/14651858.CD007400.pub3. It is not funded in New Zealand.
Oral NSAIDs: The efficacy of oral NSAIDs is well-supported by multiple studies. The effect peaks at two weeks and reduces over time.
Supplements: A systematic review concluded that the following supplements had the most evidence: L-carnitine, Pycnogenol, curcumin, Boswellia serrata extract, Curcuma longa extract, passion fruit peel extract, and collagen hydrolysate. 
===Surgery===
Total Knee Joint Replacement: This involves rResection of diseased surface, resurfacing with metal and polyethylene components. There have been no sham studies. Probably the best study is a non placebo controlled study by Skou et al who found a significant proportion still experienced chronic pain after surgery. Skou, S. T., Roos, E. M., Laursen, M. B., Rathleff, M. S., Arendt-Nielsen, L., Simonsen, O., & Rasmussen, S. (2015). A Randomized, Controlled Trial of Total Knee Replacement. New England Journal of Medicine, 373(17), 1597–1606.  While not perfect, knee replacement does reduce pain and improve quality of life compared to non surgical treatment – exercise, diet, insoles, medication. 
About 20% experience chronic pain after surgery, and the causes of this are not fully understood (but strong psychological risk factors). Unfortunately the advent of robotic surgery has not resulted in improvements in satisfaction rates. The most common risks of surgery are DVT and stiffness. 
Possible factors contributing to persistent pain following surgery are summarised by Wylde et al. M
Factor 	Examples
Biological	Sensitizing impact of long-term pain from osteoarthritisComplex Regional Pain SyndromePain originating from the hipPatellofemoral painAllergy-related problemInflammatory response
Surgical 	InfectionLocalized nerve injuryProsthetic looseningMalalignmentMalrotationIncorrect sizingInstabilityStiffness
Arthroscopic Debridement: In one of the only placebo controlled trials in all of orthopaedic surgery, this procedure was proven to be no better than sham surgery and should no longer be performed. Moseley, J. B., O’Malley, K., Petersen, N. J., Menke, T. J., Brody, B. A., Kuykendall, D. H., … Wray, N. P. (2002). A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee. New England Journal of Medicine, 347(2), 81–88. doi:10.1056/nejmoa013259 
Unicompartmental arthroplasty: Quicker recovery and improved ROM. Suitable for younger patients with low activity demands
Osteotomy: High tibial osteotomy (for varus knee). Distal femoral Osteotomy (for valgus knee). Younger patients with high activity demands and poor alignment. Again there are no sham studiesDettoni F, Bonasia DE, Castoldi F, Bruzzone M, Blonna D, Rossi R. High tibial osteotomy versus unicompartmental knee arthroplasty for medial compartment arthrosis of the knee: a review of the literature. Iowa Orthop J. 2010;30:131–140.
===Other Treatments===
Steroid Injections: No better than placebo with an increased risk of accelerated cartilage loss McAlindon TE, LaValley MP, Harvey WF, et al. Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial. JAMA 2017;317(19):1967-1975.
PRP: Initial evidence was "promising". However a recent large RCT showed no benefit over placebo.Bennell KL, Paterson KL, Metcalf BR, Duong V, Eyles J, Kasza J, Wang Y, Cicuttini F, Buchbinder R, Forbes A, Harris A, Yu SP, Connell D, Linklater J, Wang BH, Oo WM, Hunter DJ. Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial. JAMA. 2021 Nov 23;326(20):2021-2030. doi: 10.1001/jama.2021.19415. PMID: 34812863; PMCID: PMC8611484. However the methodology of the RCT was criticized. 
Dextrose Prolotherapy: A systematic review found high risk of bias and that prolotherapy was no different from platelet-rich plasma on the pain subscale at the 6-month time point, and was inferior to platelet-rich plasma at 6 months.
Genicular Nerve Ablation: A sham controlled RCT showed ablation was superior to sham ablation, however the responder rates and magnitude of response were both poor. Responder rates (defined as meeting MCID) at 3 months were 29.6% for true RF and 22.2% for sham RF. 
==References==
Category:Knee and Leg Conditions
Category:Osteoarthritis