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KNEE OSTEOARTHRITIS

What is Knee Arthritis?

  • The knee is a hinge joint connecting the thigh and lower leg. The joint is lined with articular cartilage and meniscal cartilage. Articular cartilage is the smooth, white tissue lining the ends of each bone. Knee osteoarthritis (OA) is a multifactorial disease process characterized by progressive degeneration of the joint cartilage and associated structures.
  • Although often described as "wear and tear" arthritis, knee osteoarthritis is increasingly recognized as a disease involving the entire joint. Cartilage loss is only one component of the condition. Inflammation, bone marrow lesions, meniscal degeneration, synovitis, and changes in joint mechanics all contribute to symptoms and disease progression.
  • There are several underlying mechanisms and contributing factors that can lead to degenerative osteoarthritis:
    • Mechanical Stress: Abnormal stress can cause inflammation and result in damage to the cells that line the joint (chondrocyte) leading to cell death and cartilage degradation [Jiang et al, 2023].
    • Inflammation: Chronic low-grade inflammation plays a central role in degenerative osteoarthritis of the knee. Pro-inflammatory cytokines can degrade the cartilage and exacerbate joint damage [Coaccioli et al, 2022; Chow & Chin, 2020].
    • Subchondral Bone Changes: Subchondral bone lesions and remodeling can result in abnormal blood flow to the underlying bone. This decrease in blood perfusion can further influence the disease and promote cartilage breakdown [Coaccioli et al, 2022; Olansen et al, 2024].
    • Biochemical Mediators and Mechanotransduction: Pro-inflammatory mediators and mechanical stress activate signaling pathways that can lead to further degenerative (or increased catabolysis) [Rosenberg et al, 2017; Segarra-Queralt et al, 2024].

Knee Anatomy

The knee is the largest joint in the body and consists of three compartments:

  • Medial compartment (inside of the knee)
  • Lateral compartment (outside of the knee)
  • Patellofemoral compartment (behind the kneecap)

Healthy cartilage covers the ends of the femur, tibia, and patella, allowing smooth movement with minimal friction. The menisci act as shock absorbers and help distribute load across the joint.

As osteoarthritis progresses, cartilage becomes thinner, the menisci may degenerate, bone spurs (osteophytes) can develop, and inflammation within the joint increases.

Knee osteoarthritis

What are the common risk factors for developing knee osteoarthritis?

  • Knee osteoarthritis affects millions of Americans and becomes increasingly common with age, previous injury, obesity, and certain genetic factors. Common risk factors for developing knee osteoarthritis (OA) include:
    • Age: The prevalence of knee OA increases with age, particularly in individuals over 60 years old [Allen et al, 2022].
    • Joint Injury: Previous knee injuries, such as meniscal tears or anterior cruciate ligament (ACL) injuries, significantly increase the risk of developing knee OA. This is due to altered joint mechanics and increased cartilage wear. Jobs that involve repetitive knee bending, heavy lifting, or prolonged standing are also associated with a higher risk of knee OA due to chronic mechanical stress on the joint [Blagojevic et al, 2010; Toivanen et al, 2010; Richmond et al, 2013; Georgiev & Angelov, 2019; Klussmann et al, 2010].
    • Genetics: Certain individuals appear genetically predisposed to developing osteoarthritis. A family history of OA increases the risk, suggesting a genetic predisposition to the disease [Allen et al, 2022; Ren et al, 2020].
    • Comorbidities: Conditions such as diabetes, hypertension, and metabolic syndrome are associated with an increased risk of knee OA, likely due to systemic inflammation and metabolic dysregulation [Allen et al, 2022; Ren et al, 2020].
    • Muscle Weakness: Weakness in the quadriceps and other supporting muscles around the knee can lead to joint instability and increased stress on the knee, contributing to OA development [Allen et al, 2022; Allen & Golightly, 2015].
  • Addressing these risk factors through weight management, injury prevention, and appropriate physical activity can help mitigate the risk of developing knee OA.

How do you know if you have Knee Arthritis?

  • The diagnosis of knee OA is primarily clinical, based on history and physical examination. Patients often report knee pain, inflammation and stiffness.

  • Symptoms often develop gradually over time. Symptoms may fluctuate and often worsen with increased activity. Common symptoms include:

    • Knee pain with activity
    • Stiffness after sitting or inactivity
    • Swelling
    • Loss of range of motion
    • Difficulty walking long distances
    • Pain with stairs
    • Grinding or crunching sensations
    • Reduced function and activity tolerance

  • On examination, patients can have joint line tenderness, bony enlargement, and restricted movement [Katz et al, 2021; Duong et al, 2023; Ebell, 2018]. Common findings include:

    • Joint line tenderness
    • Crepitus (grinding)
    • Reduced motion
    • Swelling
    • Muscle weakness
    • Gait abnormalities

  • Radiographs may be needed to confirm the diagnosis. Weight-bearing x-rays can show joint space narrowing, spurs (osteophytes), bone thickening (subchondral sclerosis), and cysts.

  • MRI is not routinely required but can be useful in complex cases [Katz et al, 2021; Duong et al, 2023; Ebell, 2018].

Radiograph of knee with osteoarthritis
Radiographic image (x-ray) of a knee with advanced medial compartment osteoarthritis showing joint space narrowing and sclerosis and a normal knee joint showing normal joint space.

What are the treatments for Knee Arthritis?

Nonsurgical options historically included:

  • Many patients are not ready for a joint replacement and there are a number of strategies to help manage pain until you are ready or the disease is severe enough to warrant surgery. The goal of treatment is to control the pain. Various evidence supports medications, weight loss, bracing, physical therapy, and cortisone injections.

    • Pharmacological treatments for knee osteoarthritis includes several classes of medications, each with varying levels of evidence to support their efficacy and safety.

Corticosteroid injections:

Viscosupplementation injections:

  • Viscosupplementation injections, or intra-articular hyaluronic acid injections, are commonly used for knee pain, and have been approved by the US Food and Drug Administration (FDA) since 1997 [Beaudart et al, 2020; Bannuru et al, 2015; Brophy & Fillingham, 2022].

  • Evidence supports the use of intra-articular hyaluronic acid injections for the management of knee osteoarthritis (OA) and repeated hyaluronic acid injections appear to be effective and safe [Altman et al, 2018]:
    • A meta-analysis by Wang et al. demonstrated that hyaluronic acid injections significantly improve pain and functional outcomes in knee OA patients, with few adverse events reported [Wang et al, 2004].
    • Another meta-analysis by Bannuru et al. highlighted that hyaluronic acid injections show a therapeutic trajectory, with efficacy starting at 4 weeks, peaking at 8 weeks, and maintaining a residual effect up to 24 weeks [Bannuru et al, 2011].
    • The American Academy of Orthopaedic Surgeons (AAOS) guidelines indicate that hyaluronic acid injections have a clinically meaningful effect size, although there is some inconsistency in the literature regarding their overall efficacy [Vangsness et al, 2020].
    • Maheu et al. emphasized that hyaluronic acid injections offers moderate symptomatic benefits and a good benefit/risk ratio, advocating for its inclusion in knee OA management [Maheu et al, 2019].

  • Learn more about viscosupplementation injections for knee pain here.

Orthobiologic Injections:

  • What is the evidence for platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (OA)?

  • Platelet-rich plasma (PRP) has been studied for knee osteoarthritis (OA) and can be effective in temporarily reducing pain and improving function, with recent studies highlighting the importance of platelet dose:

    • A systematic review and meta-analysis by Xiong et al. demonstrated that PRP injections significantly improve pain and functional outcomes in patients with knee OA compared to controls [Xiong et al, 2023].
    • Chu et al. conducted a randomized clinical trial comparing PRP to sham saline injections. The study found that PRP provided sustained improvements in clinical outcomes for up to 24 months, with significant differences favoring PRP over saline at all follow-up points [Chu et al, 2022].
    • Daiet al. performed a meta-analysis of randomized controlled trials and found that PRP was more effective than hyaluronic acid (HA) and saline in reducing pain and improving function at 6 and 12 months after the PRP injection. The study concluded that PRP provides significant clinical improvements in pain relief and functional outcomes [Dai et al, 2017].
    • The American Society of Pain and Neuroscience, in their STEP guidelines, supports the use of PRP for knee OA, highlighting its excellent safety profile and superior efficacy compared to HA in reducing long-term pain and improving knee function [Hunter et al, 2022].
    • A systematic review by Berrigan et al. found that higher platelet doses in PRP injections are associated with better clinical outcomes. Specifically, studies with positive outcomes had a mean platelet dose of approximately 5.5 billion platelets, whereas those without significant improvements had lower doses around 2.3 billion platelets [Berrigan et al, 2024]. This suggests that a greater platelet dose may enhance the therapeutic efficacy of PRP in knee OA and the importance of being able to count platelet doses.
    • Bansal et al. conducted a study comparing PRP to hyaluronic acid (HA) and found that a PRP dose of 10 billion platelets provided significant improvements in WOMAC and IKDC scores, as well as pain-free walking distance, with benefits persisting up to one year [Bansal et al, 2021]. This study underscores the importance of optimizing the platelet concentration in PRP formulations for sustained clinical efficacy.
    • A meta-analysis by Tao et al. demonstrated that multiple doses of PRP are more effective than a single dose in providing pain relief and functional improvement up to one year post-injection [Tao et al, 2023]. This finding supports the use of repeated PRP injections for enhanced outcomes in knee OA.
  • What is the evidence for micro-fragmented adipose tissue (MFAT) and bone marrow aspirate concentrate (BMAC) mesenchymal stem cell (MSC) injections in the treatment of knee osteoarthritis? (Learn more about MFAT injections here and BMAC injections here)
    • A study by Mautner et al. compared MFAT and BMAC injections in patients with symptomatic knee OA. Both groups showed significant improvements in pain and function. There was no significant difference in outcomes between the two groups, indicating that both MFAT and BMAC are effective for knee OA [Mautner et al, 2019].
    • The American Society of Pain and Neuroscience's STEP Guidelines also support the use of MSCs, including those derived from bone marrow and adipose tissue, for knee OA. The guidelines highlight that MSCs improve pain and function, with significant decreases in pain scores. However, the evidence for cartilage repair remains inconclusive [Hunter et al, 2022].
    • A systematic review by Keeling et al. found that BMAC injections significantly improved pain and patient-reported outcomes in knee OA patients at short- to mid-term follow-up. However, BMAC did not demonstrate clinical superiority over other biologic therapies, including PRP and MFAT [Keeling et al, 2022].

Surgical Management

  • The above are potential management tools to help with pain and function, but the definitive treatment for knee arthritis is a joint replacement (total knee replacement).
Radiograph (x-ray) after a total knee arthroplasty/replacement.
Radiograph of a right knee after a total knee replacement surgery.

What are the long-term outcomes of platelet-rich plasma (PRP) treatment for knee osteoarthritis?

The long-term outcomes of platelet-rich plasma (PRP) treatment for knee osteoarthritis (OA) are influenced by the platelet dose and the number of injections.

What is the role of higher platelet doses for the treatment of knee osteoarthritis?

  • Studies indicate that higher platelet concentrations in PRP formulations are associated with better clinical outcomes. Bansal et al. demonstrated that a PRP dose of 10 billion platelets provided significant improvements in function with benefits persisting up to one year [Bansal et al, 2021]. Similarly, Boffa et al. found that higher platelet concentrations correlated with greater improvements in function, and a lower failure rate compared to lower platelet concentrations [Boffa et al, 2024].

What is the role of multiple injections for the treatment of knee osteoarthritis?

  • There is some evidence that supports multiple PRP injections as being more effective than a single injection for long-term outcomes. Yurtbay et al. showed that multiple PRP injections resulted in better pain and function scores at 6 and 12 months compared to a single injection, although the differences were not significant at 24 months [Yurtbay et al, 2021]. Tao et al. confirmed that three doses of PRP provided superior pain relief and functional improvement up to one year compared to a single dose [Tao et al, 2023].
  • Other studies found no significant additional benefit of multiple PRP injections compared to a single PRP injection or saline injection in pain relief or functional improvement up to 12 months [Lewis et al, 2022]. This suggests that multiple injections may not provide superior outcomes compared to a single injection. In a
    systematic review by Chou and Shih that there were no significant differences in the improvement in pain scores between patients that got 1-, 2-, and 3-PRP injections [Chou & Shih, 2021]. Multiple PRP injections may increase the risk of local adverse reactions, such as knee pain and swelling, compared to single injections [Campbell et al, 2015].
  • While multiple PRP injections may be more effective than a single PRP injection at 6 and 12 months, there were no significant differences in outcomes at 24 months, suggesting that any advantage of multiple injections diminishes over time [Yurtbay et al, 2022]. In patients with advanced OA, multiple PRP injections did not improve outcomes when compared to single injections or hyaluronic acid suggesting that the efficacy of multiple injections may be limited to early-stage OA [Gormeli et al, 2017].

What is long-term efficacy of PRP for the treatment of knee osteoarthritis?

  • Chu et al. conducted a large randomized clinical trial and found that PRP injections can provide sustained improvements in clinical outcomes, including functional scores, for up to 60 months, with significant differences favoring PRP over sham saline at all follow-up points. This study highlights the long-term benefits of high dose PRP in managing knee OA [Chu et al, 2022].

frequently asked questions

There is no single best treatment. Management typically combines exercise, physical therapy, weight management, and targeted interventions based on symptom severity.

Many studies demonstrate that PRP provides longer-lasting improvements than corticosteroid injections for knee osteoarthritis.

Current evidence suggests PRP may improve symptoms and joint health, but complete cartilage regeneration has not been consistently demonstrated.

Most orthobiologic procedures are considered elective and are not currently covered by insurance.

Joint replacement is generally considered when symptoms significantly impair quality of life and conservative treatment options no longer provide adequate relief.

Maintaining a healthy weight, staying active, addressing injuries promptly, and optimizing joint mechanics may reduce the risk of osteoarthritis progression.

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