Complications and Outcomes of Nonoperative Treatment Modalities in Knee Osteoarthritis


Osteoarthritis is a slowly progressive degenerative disorder that involves damage to joint cartilage, structural changes in the bone, and inflammation of the soft tissues surrounding the joint. Osteoarthritis of the knee is the most prevalent form of osteoarthritis, symptomatically affecting 13% of women and 10% of men greater than 60 years old. , Knee osteoarthritis can threaten a patient’s ability to participate in healthy physical activity and may predispose patients to medical comorbidities and a potential loss of independence secondary to the pain and disability associated with knee arthritis.

Unfortunately, there is currently no curative treatment for osteoarthritis. As such, all nonsurgical interventions for knee osteoarthritis are palliative rather than curative. The management goals of nonoperative care should include reducing knee pain, improving daily functioning, and potentially delaying disease progression. Treatment of knee osteoarthritis includes both nonsurgical and surgical options, with the primary surgical option being either a partial (unicompartmental knee arthroplasty [UKA]) or total knee arthroplasty (TKA). Published reports have consistently described TKA as an efficacious and cost-effective means of alleviating pain, restoring function, and improving health-related quality of life. However, because it is an invasive surgical treatment, it is associated with potentially serious intraoperative and postoperative risks. Therefore, only after nonsurgical treatments have failed should TKA be considered.

In 2013, the American Academy of Orthopaedic Surgeons (AAOS) released an updated version of evidence-based guidelines regarding treatment of knee osteoarthritis ( Table 5.1 ). These guidelines are based on a systematic review of current scientific and clinical research. Strong recommendations included generalized strengthening, low-impact aerobic exercise, neuromuscular education, nonsteroidal antiinflammatory drugs (NSAIDs; oral or topical), and tramadol. Moderate recommendations included weight loss if the patient’s body mass index (BMI) is greater than 25. Inconclusive recommendations included electrotherapeutic modalities, manual or active release therapy, valgus-directing force brace, acetaminophen, opioids, pain patches, platelet-rich plasma, and arthroscopic partial meniscectomy. Of importance, these guidelines were inconclusive regarding intraarticular corticosteroids and strongly recommended against hyaluronic acid injections and glucosamine and chondroitin supplementation. However, when considering different treatment modalities for knee osteoarthritis, the orthopaedic surgeon must balance scientific evidence, personal clinical experience, and each patient’s individualized values and preferences. This will allow for shared patient and surgeon decision-making and optimal patient satisfaction. Specific nonsurgical treatment options will be discussed later, organized specifically by AAOS recommendations.


Summary of 2013 AAOS Clinical Practice Guidelines: Treatment of Osteoarthritis of the Knee

Strength of Recommendation
Strong Strengthening, low-impact aerobic exercises
Nonsteroidal antiinflammatory drugs or tramadol
Cannot recommend acupuncture
Cannot recommend glucosamine and chondroitin
Cannot recommend hyaluronic acid
Cannot recommend arthroscopy and lavage and debridement
Moderate Weight loss if body mass index >25
Cannot recommend lateral wedge insoles
Cannot recommend needle lavage
Inconclusive Physical agents (electrotherapeutic modalities)
Manual therapy
Valgus-directing force brace
Acetaminophen, opioids, pain patches
Intraarticular corticosteroids
Growth factor or platelet-rich plasma injections
Arthroscopic partial meniscectomy

AAOS , American Academy of Orthopaedic Surgeons.

Nonoperative Treatment Modalities: Strong Recommendation

Aerobic Exercise and Strength Training

Chronic pain from knee osteoarthritis can inhibit neural pathways to the surrounding musculature of the knee joint, resulting in a decrease of muscle activation and muscle mass leading to physical deconditioning and decreased quality of life. The quadriceps muscles absorb limb loading and help provide dynamic joint stability. Therefore, quadriceps weakness and abnormal mechanical joint forces have been related to the progression of knee osteoarthritis, and both are potentially modifiable by resistance training. Resistance exercises along with aerobic exercises have been illustrated to decrease pain and improve overall physical function in patients with knee osteoarthritis. Strength training administered in a variety of modes and intensities is both tolerable and effective in patients with knee osteoarthritis. It can ultimately lead to an improvement in muscle strength, walking self-efficacy, walking endurance, gait speed, stair climb/descent time, balance, and self-reported disability. In regard to aerobic exercises, walking programs, aquatic exercises, jogging in water, yoga, and tai chi have all been found to improve the function, gait pattern, and pain in patients with knee osteoarthritis. ,

Important points regarding exercise programs for patients with knee osteoarthritis include the following: (1) supervised group or individualized treatments are superior to independent exercise; (2) targeting quadriceps, hamstrings, and hip abductors for strengthening; (3) minimizing compressive joint forces; and (4) the use of a combination of strengthening, flexibility, and functional exercises. In addition, for obese patients or those with more severe degenerative changes, hydrotherapy (also known as aqua therapy ) has been found to be an effective way to strengthen muscles while minimizing joint loading. Although exercise is associated with a reduction in pain and disability for patients with knee osteoarthritis, these improvements persist only if the exercise is continued. Therefore, orthopaedic surgeons must explain to their patients that long-term involvement in exercise is necessary to maintain any clinical improvements. In addition, patients must be educated regarding the fact that exercise has not been found to prevent knee osteoarthritis. Even with consistent resistance training and aerobic exercise, patients’ pain and function may ultimately deteriorate due to the natural course of knee osteoarthritis. However, exercise regimens should still be encouraged because of the proven short-term efficacy.

Nonsteroidal Antiinflammatory Drugs

NSAIDs are commonly used for the nonoperative treatment of knee osteoarthritis. The primary effect of NSAIDs is cyclooxygenase inhibition, blocking the formation of prostaglandins, prostacyclins, and thromboxanes. The cyclooxygenase enzyme (COX) exists in two forms: COX-1 and COX-2. COX-1 is expressed in platelets, the gastrointestinal (GI) tract, and the kidneys to regulate platelet function, gastric mucosa integrity, and renal blood flow. COX-2 synthesized prostaglandins potentiate pain sensation on the central and peripheral nervous system.

There are many studies demonstrating both short- and long-term effectiveness of NSAIDs in terms of decreasing the pain associated with osteoarthritis, and patients are able to take these medications in combination with other medications (such as acetaminophen) to further potentiate pain control. A list of NSAIDs commonly used in the United States is provided in Table 5.2 . Of course, NSAIDs are not without potential side effects, such as platelet inhibition, inhibition of prostaglandin formation needed for normal GI and renal function, cardiotoxicity, and drug-induced asthmatic reactions. NSAIDs should be used at the lowest effective dose and for the shortest duration. It is vital to consider patient medical comorbidities when deciding on this treatment. For example, patients with a history of prior GI events or cardiovascular or renal impairment may want to avoid NSAIDs or strictly monitor and regular their use. In addition, orthopaedic surgeons must be aware that NSAIDs have dangerous interactions with various drugs, including anticoagulants, antihypertensive agents, antidepressants, and lithium.


Common Nonsteroidal Antiinflammatory Drugs , ,

Drug Name Characteristics & Dosing
Nonselective COX inhibitors Potential side effects include excessive bleeding, gastrointestinal tract irritation/ulceration
Aspirin Irreversibly inhibits platelet function for the life of the platelet (7–10 d)
325–650 mg q 4–6 h
Ibuprofen Synergistically potentiates analgesic properties of hydrocodone and oxycodone, shorter duration of effect
200–400 mg q 4–6 h
Naproxen Synergistically potentiates analgesic properties of hydrocodone and oxycodone
250–500 mg q 12 h
Diclofenac Also available as topical patch/gel for treatment of osteoarthritis
50 mg q 8 h
Indomethacin More frequently associated with CNS side effects (headache)
25–5 0 mg q 8–12 h
Selective COX-2 inhibitors Significantly decreased risk of gastrointestinal bleeding and ulceration. Increased risk of myocardial infarction and stroke.
Celecoxib Patients with indications for cardio protection require aspirin supplementation
200 mg once daily or 100 mg q 12 h
Meloxicam Long duration of effect
7.5–15 mg once daily

CNS , Central nervous system; COX , cyclooxygenase enzyme.

Serious GI side effects, such as peptic ulcer bleeding and perforation, have been reported in 2% to 4% of chronic NSAID users. Of importance, this risk may be decreased by half with the use of a selective cyclooxygenase-2 inhibitor (such as celecoxib). COX-2 selective inhibitors were developed to inhibit prostaglandin synthesis at sites of inflammation without disrupting the homeostatic function of the COX-1 enzyme on GI mucosa, the kidney, and platelets. Therefore, the selective COX-2 inhibitors have analgesic and antiinflammatory effects equivalent to the traditional NSAIDs with 50% to 60% less GI adverse effects and no effect on platelet function. However, orthopaedic surgeons must be aware that COX-2 inhibitors have been found to significantly increase the risk of myocardial infarction and stroke in patients with preexisting cardiac, renal, and vascular disease.

Nonoperative Treatment Modalities: Moderate Recommendation

Weight Loss

Previous studies have suggested an association of increased BMI with increased musculoskeletal pain. Increased body weight places more mechanical load on the knee joint itself, which leads to higher levels of knee pain. , Obesity can also lead to knee pain through the release of proinflammatory adipocytokines, such as adiponectin and leptin, from adipose tissue. , Weight loss is recommended for patients with symptomatic knee osteoarthritis with a BMI greater than 25. Weight loss should be obtained via diet and low-impact aerobic exercise.

Obesity not only increases a patient’s risk for knee pain but also may increase the likelihood of having knee osteoarthritis. Multiple prior studies have found an association between an increase in BMI and increased odds of knee osteoarthritis. Adipocytokines levels are generally higher in obese patients and specific adipocytokines have been thought to lead to cartilage degeneration. In addition, the formation of advanced glycation end products with obesity may be associated with increased collagen stiffness, alterations of the extracellular matrix, and decreased proteoglycans synthesis, ultimately resulting in cartilage degradation as well. Therefore, weight loss should be encouraged to decrease pain from osteoarthritis but also to decrease a patient’s risk for developing worsening osteoarthritis.

Nonoperative Treatment Modalities: Inconclusive Recommendation

Intraarticular Corticosteroid Injections

There are few prior prospective randomized controlled trials in which intraarticular corticosteroid injections were compared directly to placebo for pain relief beyond 4 weeks for knee osteoarthritis. Therefore, the AAOS 2013 clinical practice guidelines determined the use of intraarticular corticosteroids for knee osteoarthritis to be inconclusive. Intraarticular corticosteroids have been claimed to be clinically effective at providing decreased pain from knee osteoarthritis via inflammation reduction and an acceptable short-term nonsurgical treatment option ( Table 5.3 ). One particular advance of intraarticular corticosteroid injections over systemic antiinflammatories is to provide high concentrations of the corticosteroid in the synovial fluid while minimizing systemic effects. However, the efficacy and duration benefit of intraarticular steroid injections varies in the literature, with the analgesic effect usually waning over 1 to 4 weeks. In addition, there is substantial variability regarding injection technique and location, medication injected, and the level of sterility. Although the best steroid medication is not yet determined, triamcinolone hexacetonide may be more effective because of its low solubility, allowing the medication to be maintained within the joint for a longer period of time ( Table 5.3 ). In addition, a newer compound extended-release formulation of triamcinolone acetonide has been developed. When compared with the immediate-release formulation in a double-blind randomized clinical trial, the extended-release formulation was significantly superior regarding improvement of knee osteoarthritis pain at 2 through 12 weeks ( Table 5.3 ).


Comparisons of Common Intra-Articular Corticosteroid Injections

Name Strengths/Weaknesses
Triamcinolone hexacetonide Low solubility may provide longer maintained levels of medication in joint and synovium.
Repeated injections create a risk for chondrotoxicity and increase knee cartilage volume loss.
Triamcinolone hexacetonide vs. methylprednisolone Statistically significant decrease in pain favoring triamcinolone over methylprednisolone at wk 3.
Triamcinolone hexacetonide vs. betamethasone More efficacious than betamethasone at wk 1.
40 mg Extended-release formulation of triamcinolone vs. immediate-release formulation Extended-release formulation produced statistically significant pain relief over immediate-release formulation at wk 5 through 10.

Since the release of the second AAOS clinical guidelines, more recent literature has been published supporting the use of corticosteroid injections for the treatment of knee osteoarthritis. Matzkin et al. evaluated 100 patients using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score before the injection and up to 6 months postinjection. Using the minimally clinically important difference value, the WOMAC subscores for pain, stiffness, and physical function had clinically and statistically significant improvements over time when compared with baseline scores. In addition, obese patients and the patients with higher-grade osteoarthritis (Kellgren-Lawrence grades 3 or 4) had statistically significant worse scores at baseline, 6 weeks, and 3 months compared with nonobese patients and lower-grade osteoarthritis patients, respectively. In addition to this study, multiple prior studies have illustrated that patients with lower Kellgren-Lawrence grades experience greater pain relief with corticosteroid injection compared with patients with higher grades. Although intraarticular corticosteroid injections may be an acceptable short-term treatment option, lifelong treatment of knee osteoarthritis with intraarticular corticosteroid injections has not been shown to be effective. In addition, with repeat injections, there is a concern for chondrotoxicity from both the steroid and local anesthetic. , McAlindon et al. found that repeated steroid injections versus saline every 12 weeks over the course of 2 years increased knee cartilage volume loss seen on magnetic resonance imaging (MRI) and there was no significant decrease in knee pain between the steroid and saline groups.

In addition to chondrotoxicity, adverse effects of corticosteroid injections include local skin pigmentation changes; fat or skin atrophy, along with systemic effects of facial flushing; and increased liver production of glucose, increasing blood glucose levels. Diabetics should be warned and instructed to monitor their blood glucose levels appropriately. In addition, the risk of septic arthritis after corticosteroid injection has been reported to range between 1 in 3000 and 1 in 50,000.

In comparison with corticosteroid injections, intraarticular nonsteroidal antiinflammatory injections have also been shown to be an effective treatment option for knee osteoarthritis and may be safer compared with oral antiinflammatories due to less systemic side effects. The few studies that have compared intraarticular nonsteroidal injections with corticosteroid injections were unable to find any statistical differences in pain control and function. A recent double-blinded randomized controlled trial compared intraarticular injections of triamcinolone with ketorolac up to 3 months postinjection. Both triamcinolone and ketorolac significantly improved patient pain control and outcome score. This effect was greatest at week 1 and decreased over time. There was no significant difference between triamcinolone and ketorolac injections. Of importance, nonsteroidal injections are significantly cheaper than other injectables. , Therefore, nonsteroidal injections should be considered for use as a low-cost option for nonsurgical treatment of knee osteoarthritis.

Platelet-Rich Plasma

Platelet-rich plasma is an autologous concentration of platelets containing a variety of growth factors and cytokines that may possibly reduce inflammation and promote healing of damaged cartilage. , Advocates of platelet-rich plasma injections for knee osteoarthritis argue that the injection may temporarily relieve the symptoms of mild to moderate arthritis. In addition, clinical improvement has been mainly seen in younger patients without advanced degenerative disease.

In contrast, platelet-rich plasma injection for knee osteoarthritis lacks high-yield clinical data to prove clinical efficacy and scientific evidence to prove regeneration or healing of lost or damaged cartilage. There is also a paucity of information regarding the composition and biologic activity of the cells and plasma being injected and no standardized treatment protocols in which reproducible results have been demonstrated. , , Of note, the safety of platelet-rich plasma has been called into question, and instances of immediate pain and swelling postinjection have been documented. Although platelet-rich plasma has approval from the US Food and Drug Administration (FDA) for intraarticular use for knee osteoarthritis, it is considered “off label.” Platelet-rich plasma injections can be utilized as an alternative treatment option to temporarily reduce pain in knee osteoarthritis. However, because of the conflicting evidence regarding the efficacy of platelet-rich plasma, along with the elevated costs of administration, orthopaedic surgeons should be cautioned advocating for this treatment method at this point in time.

Partial Meniscectomy

Partial meniscectomy has been claimed to be an effective treatment option for patients over the age of 40 years with a meniscal tear and mild to moderate knee osteoarthritis. However, patients should be warned prior to knee arthroscopy of the low expectations for improvement. Englund et al. found that 60% to 63% of patients with Kellgren-Lawrence grade 2 or higher have a meniscus tear seen on MRI. Therefore, it has been argued that meniscal tears may be more of an incidental finding in patients with osteoarthritis, and it is unlikely that treatment with partial meniscectomy will substantially reduce a patient’s knee pain. Arthroscopic surgery for degenerative meniscus tears has been stated to have little clinical efficacy compared with therapy and other conservative management. In addition, patients must have weight-bearing radiographs prior to arthroscopy with partial meniscectomy. If significant degenerative changes are seen on radiographs, this will aid in decision-making regarding arthroscopic surgery and potential benefit.

Of importance, an interval of 6 months to 2 years between arthroscopic surgery and TKA is associated with increased adverse outcomes, including increased risk for revision, periprosthetic joint infection, stiffness requiring manipulation under anesthesia (MUA), aseptic loosening, and venous thromboembolism. Therefore, the orthopaedic surgeon should postpone definitive TKA until 6 months to 2 years have passed. In addition, surgeons may consider avoiding arthroscopic surgery altogether due to possible deleterious outcomes. Patients may be better served by nonsurgical management of their degenerative joint disease until they become candidates for TKA. Arthroscopic surgery with partial meniscectomy offers patients minimal benefit while at the same time increasing risks for poor outcomes after arthroplasty.

Nonoperative Treatment Modalities (Strong Recommendation Against)


The use of viscosupplementation for knee osteoarthritis continues to be a controversial topic within the field of orthopaedics because of weak and conflicting evidence ( Table 5.4 ). Hyaluronic acid is a naturally occurring polysaccharide in synovial fluid, which acts as a lubricant and shock absorber. , The original theory for intraarticular injection of exogenous hyaluronic acid was to increase the viscoelasticity of synovial fluid and improve knee joint homeostasis, , but the effectiveness of these injections has not been widely realized.

Jun 18, 2022 | Posted by in ORTHOPEDIC | Comments Off on Complications and Outcomes of Nonoperative Treatment Modalities in Knee Osteoarthritis

Full access? Get Clinical Tree

Get Clinical Tree app for offline access