Knee arthroplasty is the recommended treatment for end-stage DJD, however knee pain begins long before this and most orthopedic surgeons will manage patients for years before recommending surgery. There are many treatment modalities with varying levels of clinical-evidence to support or oppose its practice. The AAOS has developed Clinical Practice Guidelines for knee osteoarthritis to help direct surgeons toward the best evidence-based care. We will look at some of the common non-arthroplasty treatment options for patients with knee arthritis.
Before looking at treatments, its important to recognize the difference between the clinical and statistical significance reported in studies. Statistical significance = p < 0.05, and this reflects the probability that any difference (big or small) between two groups is random. Importantly, larger and larger groups will increase the statistical power of comparison, and therefore smaller and smaller differences between groups will become statistically significant. The clinical significance (ie a pain level of 1 out of 10 versus 2 out of 10) is independent of group size. Improving pain by 1 point either matters or it doesn't, regardless of asking 100 or 1000 people. Now comparing the statistical versus clinical significance. If a study finds a statistically significant difference in pain level of 0.1 on a 0 – 10 scale, it doesn’t mean that this value is clinically significant, if its been predetermined that only a difference of 2.0 points or more improves patient satisfaction). Many of the nonoperative treatment studies are able to enroll large numbers of patients, which is great, however it also facilitates the reporting of statistical significance, even if the actually difference in values has no clinically significant correlate.
As a reference for common outcome scores, the clinically significant difference in the Visual Analog Scale (10 cm line that patients use to rate pain) is 2 cm, while the WOMAC survey (score 0 – 100 that evaluates pain and function) requires a difference of 9 points for clinical significance.
1. Rehabilitation
Rehabilitation involves muscle strengthening, low impact aerobic exercise, coordination training, and stretching. Remember that knee kinematics are determined by a balance of muscle strength, soft tissue tension and articular geometry. Rehab successfully improves knee kinematics and patellar tracking in particular. 5 out of 7 well conducted studies showed benefit for pain and function. Looking various exercises, both weight-bearing and non-weight bearing exercises, isometric/isotonic/isokinetic exercises all demonstrated superior improvement over control. The general idea is that aerobic conditioning, muscle-strengthening, regular activity and balance training are all effective treatments for older adults with arthritis [1-7].
A cane or walker can also provide significant relief. It is demonstrated that assisted devices can decrease joint reactive force by 50%.
2. Weight Loss
Studies have demonstrated statistical improvement in pain and function scores, with some signs of clinically significant improvement as well. Logically it makes sense as 1 lbs weight loss is about 5 lbs of stress off the knee. However, some studies do not show significant clinical improvement [8] [9] [10].
Diet and exercise combined show improved outcomes in function. Groen et al. suggests bariatric surgery improved knee function and pain possibly delaying the need for TKA [11].
3. Glucosamine, Chondroitin
Not recommended as the AAOS Clinical Practice Guidelines examined 21 studies comparing placebo to glucosamine and failed to show clinically significant improvements (only 11 of 52 outcomes showed improvement with glucosamine). Meta-analysis did not show any significant differences.
Chondroitin showed some statistical difference but not translated into meaningful clinical difference. The GAIT trial published in the NEJM examined 1600 patients in a RCT and showed 50% improvement with placebo after 6 months, and an 80% response rate with the Glucosamine-Chondroitin supplement [12].
4. NSAIDs
NSAIDS are recommended with strong evidence, but make sure it is safely prescribed as chronic use can effect the gastric mucosa, platelet function, and renal function. This risk profile depends on the type of NSAID. There are Non-Selective NSAIDS (COX-1,2 inhibitors) and Selective COX-2 NSAIDS.
Non-Selective NSAIDS: Naproxen (Aleve), Ibuprofen (Motrin, Advil), Meloxicam (Mobic). These have moderate GI risk, lower cardiovascular risk. Naproxen has the lowest cardiac risk.
Selective COX-2 Inhibitors: Celecoxib (Celebrex), and Vioxx (withdrawn). These target inflammation and pain with less risk for gastric ulceration. Large database analysis suggests that chronic use of these increases risk for heart attach and stroke (the theory is that blocking COX-2 in blood vessels decreases prostacyclin, which is important for preventing platelet aggregation and vasoconstriction).
Tylenol. Not a true NSAID, as it works in the central nervous system, and does not have a direct effect on inflammation. Tylenol appears to have a better side effect profile than NSAIDS, yet there isn’t good evidence to suggest equivalent (or any) anti-inflammatory properties.
5. Acetaminophen
Not a true NSAID, as it works in the central nervous system, and does not have a direct effect on inflammation. Tylenol appears to have a better side effect profile than NSAIDS, yet there isn’t good evidence to suggest equivalent (or any) anti-inflammatory properties [14].
One RCT comparing acetaminophen to placebo found 50% improvement in both groups, although the acetaminophen group was limited to 400 mg daily (the current accepted daily max is 3000 mg).
6. Injections
Steroid. There are few placebo controlled studies for intraarticular steroid injections [15] [16, 17]. One study found statistical but not clinical improvement at 4 weeks on WOMAC but no difference by 12 weeks [18]. Other studies failed to find significant evidence for improvement compared with needle lavage or viscosupplement. Another important consideration is the non-medical purpose of such injections. Many surgeons use injections as a means to get to know their patients, a way to offer them a service without suggesting surgery upon their first meeting. Some epidemiologic data supports the use of injections for such purposes. There is a wide variation in the rates of injection among Medicare patients, from 1 in 115 (high rate) to 1 in 1000 [19]. The highest rates of injection correlated with the areas with the highest density of doctors (not orthopedic surgeons specifically), with rates of injection increasing 3x over the past 15 years, suggesting there are economic or social forces beyond medical need affecting utilization. Orthopedic surgeons administer about 59% of injections. While certainly less expensive then performing a knee arthroplasty, injections do come at a cost: $69 per injection and $80,000,000 per year nationally [20].
Viscosupplement. The AAOS strong recommends “against” the use of viscosupplements based on a number of RCT. While some studies demonstrated statistical improvements, no gains were proven to be clinically relevant [15]. Similar to the steroid injections, roughly 50% of patients with mild to moderate OA report satisfaction with the injection (yet no difference from placebo). Its therefore important to recognize the placebo effect of these medications, patients improve, but arguably the high cost of the viscosupplement is not justified (average injection costs $180, almost 3x more than steroid). Interestingly a review paper compared placebo trials and studies without a placebo (“open-label” study) and found significantly less impressive results with the placebo trials [16].
There is unclear benefit tied directly to the type of injection, although injections overall appear to help many patients, in part from the placebo effect. So if it helps some people, for whatever reason, is there any harm in giving it, even if it only helps 50% of people, for a few weeks at most? There are studies that suggest that recent injections can increase the risk for periprosthetic joint infection in TKA if given within 3 months of surgery. Cost is another. Annual cost of HA injections is about $207 million.
There are many brands for the viscosupplmentation, but they are all hyaluronic acid.
Orthovisc = hyaluronan
Synvisc = hylan G-F 20. This somes as either a single shot (Synvisc-One) or three shots given over the course of a month.
Hyalgan = hyaluronate
Fermathron plus - produced from the bacterium Streptococcus equi
7. Arthroscopy
There is strong evidence against the use of arthroscopy for the treatment of OA.
Moseley et al is a well-known study published in the New England Journal of medicine that randomized patients to scope or no scope and followed them from 2 weeks to 2 years and found no improved pain or function [23]. While the study received public recognition due to its impressive attention to detail: placebo patients received real anesthesia and a skin incision, water was splashed on the floor and a simulated debridement was played on a monitor while no arthroscope was actually inserted...the overall study design was more flawed: 44% of patients declined to participate and those that did participate were likely to be white, younger and have more severe arthritis, suggesting potential bias.
Similar RCT have also evaluated the efficacy of arthroscopic debridement for OA and failed to identify significant benefit over PT or medical management [24]. A meta-analysis found some signs of pain relieve at 3 or 6 months, however, this change was not clinically significant [25].
When arthroscopy was performed within 6 months of TKA, rates of infection (and stiffness) increased, emphasizing the outcomes from knee injections, which suggest that you don’t want to be messing around with the knee before implanting metal [26].
REFERENCES
1. Deyle, G.D., et al., Effectiveness of manual physical therapy and exercise in osteoarthritis of the knee. A randomized, controlled trial. Ann Intern Med, 2000. 132(3): p. 173-81.
2. Jan, M.H., et al., Investigation of clinical effects of high- and low-resistance training for patients with knee osteoarthritis: a randomized controlled trial. Phys Ther, 2008. 88(4): p. 427-36.
3. Silva, L.E., et al., Hydrotherapy versus conventional land-based exercise for the management of patients with osteoarthritis of the knee: a randomized clinical trial. Phys Ther, 2008. 88(1): p. 12-21.
4. O'Reilly, S.C., K.R. Muir, and M. Doherty, Effectiveness of home exercise on pain and disability from osteoarthritis of the knee: a randomised controlled trial. Ann Rheum Dis, 1999. 58(1): p. 15-9.
5. Lin, D.H., et al., Efficacy of 2 non-weight-bearing interventions, proprioception training versus strength training, for patients with knee osteoarthritis: a randomized clinical trial. J Orthop Sports Phys Ther, 2009. 39(6): p. 450-7.
6. Fitzgerald, G.K., et al., Agility and perturbation training techniques in exercise therapy for reducing pain and improving function in people with knee osteoarthritis: a randomized clinical trial. Phys Ther, 2011. 91(4): p. 452-69.
7. Kovar, P.A., et al., Supervised fitness walking in patients with osteoarthritis of the knee. A randomized, controlled trial. Ann Intern Med, 1992. 116(7): p. 529-34.
8. Miller, G.D., et al., Intensive weight loss program improves physical function in older obese adults with knee osteoarthritis. Obesity (Silver Spring), 2006. 14(7): p. 1219-30.
9. Focht, B.C., et al., Exercise, self-efficacy, and mobility performance in overweight and obese older adults with knee osteoarthritis. Arthritis Rheum, 2005. 53(5): p. 659-65.
10. Rejeski, W.J., et al., Obese, older adults with knee osteoarthritis: weight loss, exercise, and quality of life. Health Psychol, 2002. 21(5): p. 419-26.
11. Groen, V.A., et al., Effects of bariatric surgery for knee complaints in (morbidly) obese adult patients: a systematic review. Obes Rev, 2015. 16(2): p. 161-70.
12. Clegg, D.O., et al., Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med, 2006. 354(8): p. 795-808.
13. Scarpignato, C., et al., Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis--an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks. BMC Med, 2015. 13: p. 55.
14. Miceli-Richard, C., et al., Paracetamol in osteoarthritis of the knee. Ann Rheum Dis, 2004. 63(8): p. 923-30.
15. van der Weegen, W., et al., No difference between intra-articular injection of hyaluronic acid and placebo for mild to moderate knee osteoarthritis: a randomized, controlled, double-blind trial. J Arthroplasty, 2015. 30(5): p. 754-7.
16. Jevsevar, D., et al., Viscosupplementation for Osteoarthritis of the Knee: A Systematic Review of the Evidence. J Bone Joint Surg Am, 2015. 97(24): p. 2047-60.
17. Raynauld, J.P., et al., Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum, 2003. 48(2): p. 370-7.
18. Jones, A. and M. Doherty, Intra-articular corticosteroids are effective in osteoarthritis but there are no clinical predictors of response. Ann Rheum Dis, 1996. 55(11): p. 829-32.
19. Gaffney, K., J. Ledingham, and J.D. Perry, Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response. Ann Rheum Dis, 1995. 54(5): p. 379-81.
20. Chao, J., et al., Inflammatory characteristics on ultrasound predict poorer longterm response to intraarticular corticosteroid injections in knee osteoarthritis. J Rheumatol, 2010. 37(3): p. 650-5.
21. Schmajuk, G., K.J. Bozic, and J. Yazdany, Using Medicare data to understand low-value health care: the case of intra-articular hyaluronic acid injections. JAMA Intern Med, 2014. 174(10): p. 1702-4.
22. Koenig, K.M., et al., The Use of Hyaluronic Acid and Corticosteroid Injections Among Medicare Patients With Knee Osteoarthritis. J Arthroplasty, 2016. 31(2): p. 351-5.
23. Moseley, J.B., et al., A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med, 2002. 347(2): p. 81-8.
24. Kirkley, A., et al., A randomized trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med, 2008. 359(11): p. 1097-107.
25. Thorlund, J.B., et al., Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms. Br J Sports Med, 2015. 49(19): p. 1229-35.
26. Werner, B.C., et al., Total Knee Arthroplasty Within Six Months After Knee Arthroscopy Is Associated With Increased Postoperative Complications. J Arthroplasty, 2015. 30(8): p. 1313-6.