Hyaluronic Acid Injections for Knee Osteoarthritis

Title XVIII of the Social Security Act, §1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member

Title XVIII of the Social Security Act, §1862(a)(7) states Medicare will not cover any services or procedures associated with routine physical checkups

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §50.3 Incident-to Requirements and §50.4.1 Approved Use of Drug

CMS Internet-Only Manual, Pub. 100-08, Medicare Program Integrity Manual, Chapter 13, §13.5.4 Reasonable and Necessary Provision in an LCD

In the United States (U.S.), osteoarthritis (OA) is the most common type of arthritis and joint disorder, and the knee is the most frequently involved symptomatic joint.¹

Degenerative joint disease, usually termed OA, of the knee is characterized by progressive destruction of the articular cartilage that lines the knee joint, involvement of the subchondral bone surfaces and synovium, and associated pain, immobility, reduced function, and decreased ability to complete activities of daily living (ADLs).² Knee OA is a chronic, debilitating condition that occurs predominantly among older adults and affects a large share of the population worldwide. It is the predominant form of arthritis and the leading cause of disability in the U.S.³

Hyaluronic acid (HA) is a glycosaminoglycan component of synovial fluid that provides lubrication and shock absorption within the knee joint.⁴ HA occurs naturally in synovial fluid, where it contributes to the viscoelastic properties of the joint and helps protect cartilage from mechanical degradation. HA has been shown to provide anti-inflammatory and chondroprotective effects, increase proteoglycan and HA synthesis, and reduce nerve impulses and nerve sensitivity associated with OA pain.⁵ HA production is generally reduced and may be of poorer quality in OA, which may exacerbate inflammation. Intra-articular HA is intended to replace depleted or poor-quality HA in the joint. HA is commercially prepared and available for injection, with products differing by molecular weight and cross-linkage.

HA injections may reduce cartilage breakdown associated with loss of cartilage oligomeric matrix protein and may also reduce inflammatory cytokines, such as interleukin-1.¹

HA is also known as hyaluronan or hyaluronate. Intra-articular injection of HA is also known as viscosupplementation. Viscosupplementation involves the injection of a high-molecular-weight, hyaluronan-containing compound into the joint, where it functions as a viscoelastic glycosaminoglycan.⁶

Patients with knee OA who do not respond to conservative treatments may be candidates for intra-articular HA for treatment of knee OA. Several viscosupplementation products have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of pain associated with knee OA in patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics, such as acetaminophen.

Covered Indications

Various Hyaluronan preparations (viscosupplementation) for intra-articular injections of the knee are considered reasonable and necessary when ALL of the following criteria documented in the medical record are met:

1. Symptomatic knee OA. Pain that interferes with functional activities (such as ambulation and prolonged standing).

2. The diagnosis is supported by radiographic evidence of knee OA, for example, joint space narrowing, subchondral sclerosis, osteophytes, and subchondral cysts.

3. Trial and failure or contraindication of at least 3 months of conservative therapy:

• Non-pharmacologic therapy (e.g., physical therapy, exercise, weight management, self-management programs, knee brace, cane), and,
• Pharmacologic therapy (e.g., acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) (oral, topical), topical capsaicin)

4. Failure of or contraindication to intra-articular glucocorticoid injections.

For patients who have responded to a prior series, a REPEAT* series of viscosupplement therapy is considered reasonable and necessary when ALL of the following are met:

• Patient continues to meet initial criteria
• Symptoms have recurred
• Patient has experienced improvement in pain and functional capacity following the previous series of injections
• At least 6 months have elapsed since the prior series of injections

* A series is defined as a set of injections for each joint and each treatment as per the FDA prescribing information

Limitations

Services that are not reasonable and necessary and cannot be covered by Medicare are the following:

1. The dose and frequency of administration should be consistent with the FDA approved labeling. Doses and frequencies that exceed the FDA recommended dosage/frequency as per the prescribing information, are considered not reasonable and necessary and not covered by Medicare.

2. Initiation of a repeat series of treatment when at least 6 months have not elapsed since the prior series of injections is considered not reasonable and necessary and not covered.

3. It is considered not reasonable and necessary as the initial treatment of knee OA.

4. It is contraindicated with infections or skin disease in the area of the injection site or joint and considered not reasonable and necessary and not covered by Medicare.

5. It is contraindicated to administer these products if you are allergic to hyaluronate products.

6. A diagnosis other than OA is considered not reasonable and necessary and not covered by Medicare.

7. When there was no improvement in knee pain and functional improvement from a previous series of injections, a repeat series of injections will be considered not reasonable and necessary and will not be covered.

8. Imaging procedures for the purpose of needle guidance that may be considered reasonable and necessary are ultrasound or fluoroscopy. The documentation must support why imaging is needed for needle guidance and insertion. Other imaging modalities (e.g., computed tomography (CT) scan, magnetic resonance imaging (MRI), arthrography) for the purpose of needle guidance and insertion will be considered not reasonable and necessary and not covered by Medicare.

The evidence for intra-articular HA injections in knee OA treatment includes a significant body of evidence, including systematic reviews (SRs), meta-analyses, and randomized controlled trials (RCTs) with outcomes such as pain, function, stiffness, Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, quality of life (QoL), structural changes, direct or indirect treatment comparisons, and safety. The results of the studies demonstrate a reasonable safety profile, but clinical efficacy findings are heterogeneous. Multiple SRs showed some positive effect of HA over comparable treatments, but there has been considerable inconsistency in the degree and relevance of this effect. There has also been substantial variation among studies that enrolled different patient groups, used different HA formulations, varied comparators, and differed in methodology and approach.

Clinical Effectiveness

Across the included literature, the outcomes primarily studied were pain and physical function. In multiple SRs, intra-articular HA injections showed statistically significant improvement in pain and physical function in comparison to placebo, with the greatest benefit observed in patients with early-stage disease and milder radiographic OA.^7,8 The mechanistic evidence summarized by Ferkel et al. (2023) and Sherman et al. (2025) also provides support and insights into the analgesic and anti-inflammatory effects of intra-articular HA injections, which may arise through intra-articular HA’s ability to modulate the production of many inflammatory mediators, decreasing the production of degradative enzymes, and restoration of synovial fluid viscoelasticity.^9,10

It remains unclear, however, whether intra-articular HA injections lead to clinically meaningful improvements. Many studies have shown statistically significant benefits when HA is used as a treatment for knee OA, but the magnitude of effect varies widely across SRs. Pereira et al. (2025), in a SR and network meta-analysis focused solely on large RCTs, concluded that despite statistical superiority over placebo, improvements in pain relief and physical function did not exceed prespecified thresholds for minimal clinically important differences; additionally, most large trials investigating intra-articular treatments for knee OA were at high risk of bias.¹¹

In a more recent RCT studying a newer HA formulation, Bihlet et al. (2026) did not demonstrate superiority on the primary efficacy endpoints. The authors reported no differences between JTA-004, Synvisc-One, and saline.¹² Another RCT by Chen et al. (2026) found that a single injection of JETKNEE did not show superiority to placebo for the primary outcome of Visual Analogue Scale (VAS) pain, but demonstrated improvements in secondary functional outcomes for up to six months in patients with knee OA.¹³ Treatment effects are not consistently shown across studies, although intra-articular HA injections may provide some symptomatic relief in patients with knee OA.

Likewise, several SRs and RCTs achieved statistically significant, but not necessarily clinically meaningful, improvements in stiffness, WOMAC scores, and VAS pain scores. The consistency and magnitude of benefit varied across patient groups.^7,8

Evidence on health-related QoL was limited, with few studies evaluating validated QoL instruments as primary endpoints. The available findings were based mainly on secondary outcome analyses. Although some studies reported improvement in QoL, the current evidence does not support strong conclusions about the direct impact of intra-articular HA injections on patient-reported health status.

Structural and Biomarker Outcomes

The evidence for intra-articular HA’s role in cartilage preservation or modification of the disease course is sparse. Ferkel et al. (2023) and Sherman et al. (2025) summarized evidence supporting numerous mechanisms through which intra-articular HA preparations may provide clinical benefit in knee OA, including the significant role of HA molecular weight in effectiveness. Chondroprotection was the most frequently reported mechanism, along with inhibition of matrix metalloproteinases, delayed progression of the inflammatory cascade in the synovial joint through inhibition of various inflammatory mediators, and an analgesic effect through the action of nociceptors. These mechanisms provide a biologically plausible basis by which HA may influence cartilage breakdown.⁹

Nonetheless, clinical evidence supporting these mechanisms remains limited. A study conducted by Küçükakkaş et al. (2022) found an increase in the thickness of femoral cartilage following HA therapy, and earlier, Ishijima et al. (2022) recorded changes in urinary CTX-II levels, a biomarker for cartilage degradation.^14,15 Yang and Chen (2023) also observed decreased levels of inflammatory markers in patients administered combinations including HA.¹⁶ However, these findings are based on imaging and urinary markers rather than data demonstrating delayed structural progression of osteoarthritis or modification of the disease course.

Comparative Effectiveness

The relative effectiveness of HA varies depending on the comparator intervention. Several SRs and network meta-analyses concluded that HA injections did not establish superiority over platelet-rich plasma (PRP) for improvement in pain and physical function at intermediate- and long-term follow-up.^17,18,19,20 HA yielded similar results when compared with corticosteroids, at intermediate-term follow-up.^19,22 However, onset of benefit was longer with HA.

Evidence on HA with oral NSAIDs and polynucleotide injections was scarce but indicated comparable symptomatic improvement.^15,23 In most studies, HA combined with either PRP injections or polynucleotides led to greater improvement than HA alone. However, these studies could not isolate the effect of the HA element to the overall observed effects.^16,24

The comparator interventions themselves differed widely across studies in terms of their concentration, content, activation and preparation methods, injection volume, and dosing schedules, which limit the applicability and consistency of the estimates.^16,24

While the sparse evidence on HA comparative effectiveness does not demonstrate that HA provides consistently greater improvement in knee OA outcomes than other interventions like PRP, polynucleotides, or oral NSAIDs when used alone, mainly due to the heterogeneity and inconsistency in the evidence, it also does not suggest that HA is consistently superior to other injectable treatments for knee OA.

Safety

In contrast to the variable efficacy results, the safety profile of HA was consistent across SRs and RCTs. Adverse events were generally mild, transient, and localized to the injection site, and serious adverse events were rare.^7,8,17,18,21 Placebo-controlled and active-comparator studies similarly described good tolerability and lack of evidence for increased serious adverse events attributable to HA treatment.^{12,13,22,23,24} Therefore, the favorable safety profile of HA injections is the strongest and most consistent finding across the available evidence.

Kolasinski et al. (2020) developed guidelines and recommendations for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients’ values, preferences, and comorbidities. Many providers want the option of using HA injections when glucocorticoid injections or other interventions fail to adequately control local joint symptoms. The conditional recommendation is consistent with the use of HA injections, in the context of shared decision-making that recognizes the limited evidence of benefit, when other alternatives have been exhausted or have failed to provide satisfactory benefit.²⁵

Maheu, et al. (2019) conducted a literature review to determine the strength of evidence in support of the efficacy and safety of intra-articular HA, from RCTs and meta-analyses. The results of their analysis showed that intra-articular HA provides a moderate symptomatic benefit to knee OA patients and without major safety concerns. In fact, intra-articular HA may offer 1 of the best benefit/risk ratios among pharmacologic options, as measured by improvements in knee OA health outcomes, overall gain in quality adjusted life years and substantial delays in time to total knee replacement (TKR). They concluded by advocating for the consideration of recommending intra-articular HA injection as a treatment option in the management of knee OA, tailored by disease stage and patient phenotype. Further research efforts should focus on identification of OA patient subgroups that demonstrate a more robust response to intra-articular HA, determination of long term effects of repeat intra-articular HA injections on patient reported outcomes and TKR-sparing effect, further elucidation of disease-modifying effects, and the potential for combination therapy with other pharmacologic and non-pharmacologic therapies to optimize the management of knee OA.⁴

Newberry et al. (2015) conducted a review of the evidence on whether intra-articular HA injections in individuals with knee OA improve function and QoL and delay or prevent the need for TKR, specifically among individuals age 65 and older. They concluded that RCTs enrolling older participants showed a small, statistically significant effect of HA on function and relatively few serious adverse events; however, no studies limited participation to individuals 65 years or older. No conclusions can be drawn from the available literature on delay or avoidance of TKR with HA. Studies comparing large numbers of treated and untreated individuals, preferably using a randomized design, are needed to answer this question.²

The American Academy of Orthopaedic Surgeons (AAOS) Management of Osteoarthritis of the Knee (Non-Arthroplasty) Evidence-Based Clinical Practice Guideline, adopted August 31, 2021, is based on a SR of the available scientific and clinical information and accepted approaches to treatment and/or diagnosis. Twenty-eight studies (17 high-strength and 11 moderate-strength) assessed intra-articular HA injections compared with controls. Analyses stratified by molecular weight found no significant differences among viscosupplementation formulations. Some studies demonstrated a statistical benefit with the use of HA but did not meet the threshold for a minimally clinically meaningful difference, leading to the conclusion that viscosupplementation may represent a viable option for some patients who have failed other treatments when appropriately indicated. The number needed to treat to see a tangible benefit from HA was 17 patients. Furthermore, this difference was most evident at 6 weeks and 3 months. The 2021 version of this guideline found that statistically significant improvements were associated with high-molecular-weight cross-linked HA, but when compared with mid-range molecular weight, statistical significance was not maintained. This newer analysis did not demonstrate clinically relevant differences compared with controls. However, because previous research reported benefits with its use, the group felt that a specific subset of patients might benefit from HA. The HA recommendation was downgraded to Moderate Strength of recommendation due to lack of generalized results. HA intra-articular injection(s) is not recommended for routine use in the treatment of symptomatic knee OA. Currently, intra-articular treatments are commonly used to treat symptomatic knee OA; therefore, there should be no issues implementing this recommendation because it does not represent a major change in clinical practice and provides further evidence to support and guide these practices. Future research in this area should include detailed OA characterization, including subgroup analyses and OA severity stratification.²⁶

Bannuru, et al. (2016) conducted a SR on RCTs and meta-analyses to examine the risks of HA compared with intra-articular placebo and investigated whether the risks vary among individual HA preparations. They identified 74 studies involving 13,032 participants aged between 45 and 75 years. The overall incidence of local reactions reported across all products was 8.5%. Commonly reported adverse events (AEs) were transient local reactions, such as pain, swelling and arthralgia, which subsided rapidly. They concluded that given the very low incidence of any particular AEs, that HA products are relatively well tolerated. These products have a similar safety profile compared to each other.³

Bannuru, et al. (2015) examined the efficacy of treatments of primary knee OA using a network meta-analysis design, which estimates relative effects of all treatments against each other. For pain, all interventions significantly outperformed oral placebo, with effect sizes from 0.63 for the most efficacious treatment (HA) to 0.18 for the least efficacious treatment (acetaminophen). For function, all interventions except intra-articular corticosteroids were significantly superior to oral placebo. For stiffness, most of the treatments did not significantly differ from one another.²⁷

Campbell, et al. (2015) conducted a systematic literature review of meta-analyses comparing treatment of knee OA with intra-articular viscosupplementation (intra-articular HA) versus oral NSAIDs, intra-articular corticosteroids, intra-articular PRP, or intra-articular placebo to determine which meta-analyses provide the best current evidence and identify potential causes of discordance. The available evidence shows that intra-articular HA provides small but clinically relevant improvements in knee pain and function when compared with intra-articular placebo. Although there were no major clinical differences in the efficacy of intra-articular HA versus oral NSAIDs in relieving knee pain and restoring function, the fact that intra-articular HA has a more favorable side-effect profile than oral NSAIDs makes intra-articular HA a good option for patients unable to tolerate oral NSAIDs. Both intra-articular HA and intra-articular corticosteroids were effective in controlling pain, with steroids providing better short-term relief and HA providing more long-term relief starting in the 5 to 13-week post injection period and lasting for up to 26 weeks. Regarding intra-articular HA versus intra-articular PRP, intra-articular HA improved knee function at 2 and 6 months after injection but the effects were less robust than those of intra-articular PRP. Intra-articular HA in terms of pain and function may be a better treatment option as more high quality randomized, double-blinded studies are needed to compare the effects of PRP versus other treatments before it can be fully endorsed as a viable universal option for patients with knee OA. They concluded the current highest level of evidence suggests that intra-articular HA is a viable option for patients with knee OA. Its use results in improvements in knee pain and function that can persist for up to 26 weeks in comparison with other treatment modalities. Intra-articular HA has been shown to have a good safety profile, and its use should be considered in patients with early knee OA.⁶

Berkoff, et al. (2012) conducted a peer-reviewed literature search to compare the accuracy of intra-articular large joint injections with imaging guidance versus conventional anatomical guidance. Numerous imaging modalities may be used to aid the clinician in identifying the correct trajectory for intra-articular injections including ultrasound, fluoroscopy, CT, and MRI. The results of the current analysis demonstrate that use of imaging guidance improves the accuracy of intra-articular injection in large joints including the knee. Furthermore, the use of ultrasound guidance specifically at the knee greatly increases the likelihood of correct needle placement. Ultrasound guidance of knee injections resulted in better accuracy than anatomical guidance (95.8% versus 77.8%, P < 0.001), yielding an odds ratio of 6.4 (95% confidence interval 2.9-14).²⁸

Ong, et al. (2016) conducted a retrospective observational study design based on the 5% sample of Part B Medicare data (carrier/physician claims) from 2005 to 2012. The 5% Part B Medicare data (2005-2012) were used to identify knee OA patients who underwent knee arthroplasty (KA). The time from diagnosis of OA to KA was compared between patients with HA injections and without (no HA) intra-articular HA use. The “HA” cohort was associated with a longer time to KA of 8.7 months (95% confidence interval: 8.3 – 9.1 months; P < 0.001) compared with the “no HA” cohort. Their analysis of a large, elderly, knee OA population showed a significantly longer time from diagnosis of OA to KA for those who were treated with intra-articular HA. It is unclear if the extended time may lead to less KA utilization or whether the delay could provide additional time for patients to better address or control preexisting conditions before KA, which could aid in reducing postoperative morbidity.²⁹

Newberry, et al. (2015) conducted a SR of the effectiveness of HA in the treatment of severe degenerative joint disease of the knee. The Coverage and Analysis Group at the Centers for Medicare and Medicaid Services (CMS) requested from The Technology Assessment Program (TAP) at the Agency for Healthcare Research and Quality (AHRQ), a review of the evidence that intra-articular injections of HA in individuals with degenerative joint disease (OA [HA]) of the knee improve function and QoL and that they delay or prevent the need for TKR, specifically for individuals age 65 and over. The results of the study noted only 1 RCT reported on delay or avoidance of TKR as a pre-specified outcome of interest and found a non-statistically significantly longer delay of TKR compared with placebo; 2 RCTs reported TKR only as a secondary outcome; and 13 published observational studies reported on TKR as an outcome in HA-treated participants.

Eighteen RCTs that enrolled participants of average age 65 or older reported on functional outcomes of intra-articular HA injection: pooled analysis of 10 sham-injection placebo-controlled, assessor-blinded trials showed a standardized mean difference of -0.23 (95% CI -0.34, -0.02) significantly favoring HA at 6 month follow-up. Durability of effect could not be assessed because of the short duration of most studies. Too few head-to-head trials were available to assess superiority of 1 product over another. Three RCTs that compared changes in QoL/Health-Related QoL between HA- and placebo-treated participants reported no differences between active treatment and placebo. Two recent large, good quality SRs that conducted meta-analysis of the effects of HA on pain and function (pooling 71 and 52 RCTs for the outcome of pain, respectively) showed a significant and clinically important effect of HA on both outcomes among adults of all ages, but a subgroup analysis that included only the largest double-blind placebo-controlled studies reduced the average effect of HA to less than the prespecified minimum clinically important difference. Studies of intra-articular HA reported few serious adverse events, with no statistically significant difference in the rates of serious or non-serious adverse events between HA- and placebo-treated groups.

They concluded that trials enrolling older participants show a small, statistically significant effect of HA on function and relatively few serious adverse events; however, no studies limited participation to those 65 years or older. No conclusions can be drawn from the available literature on delay or avoidance of TKR through the use of HA. Studies that can compare large numbers of treated and untreated individuals, preferably with a randomized design, are needed to answer this question.²

Kolasinski, et al. (2020) developed an evidence-based guideline for the comprehensive management of OA as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA. Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies. In OA generally, intra-articular glucocorticoid injection is conditionally recommended over other forms of intra-articular injection, including HA preparations. Head-to-head comparisons are few, but the evidence for efficacy of glucocorticoid injections is of considerably higher quality than that for other agents.

Many providers want the option of using HA injections when glucocorticoid injections or other interventions fail to adequately control local joint symptoms. In clinical practice, the choice to use HA injections in the knee OA patient who has had an inadequate response to nonpharmacologic therapies, topical and oral NSAIDs, and intra-articular steroids may be viewed more favorably than offering no intervention, particularly given the impact of the contextual effects of intra-articular HA injections. The conditional recommendation against is consistent with the use of HA injections, in the context of shared decision-making that recognizes the limited evidence of benefit of this treatment, when other alternatives have been exhausted or failed to provide satisfactory benefit.²⁵

Trojian, et al. (2016) performed a network meta-analysis of the relevant literature to determine if there is a benefit from HA as compared with intra-articular corticosteroid and intra-articular placebo based on the evaluation of treatment effect by examining the number of subjects within a treatment arm that met the Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria, which is different and more relevant than methods used in other reviews which examined if the average change across the treatment groups was clinically different. Trojian et al. concluded that there was a small but statistically significant improvement for the group of subjects treated with HA injections compared with those treated with intra-articular corticosteroid or intra-articular placebo injections with regard to pain and function as assessed by the relevant WOMAC subscales. The statistically significant results that we have identified for HA versus intra-articular corticosteroid and intra-articular placebo also represent a clinically relevant difference.

The American Medical Society for Sport Medicine (AMSSM) recommends the use of HA for the appropriate patients with knee OA. “We RECOMMEND viscosupplementation injections for K-L grade ll-lll knee OA in those patients above the age of 60 years based on HIGH quality evidence demonstrating benefit using OMERACT-OARSI Responder Rating.” But the evidence should be downgraded because of indirectness for those younger than 60 years. “We SUGGEST viscosupplementation injections for knee OA for those under the age of 60 years based on MODERATE quality evidence due to response of treatment in those over 60 years of age.”³⁰

Strand, et al. (2015) performed a meta-analysis for randomized, sham controlled trials of intra-articular HA injection for treatment of knee OA. All sham-controlled trials used saline injections as a control. Viscosupplementation resulted in very large treatment effects between 4 and 26 weeks for knee pain and function compared to preinjection values, with standardized mean difference values ranging from 1.07 to 1.37 (all P < 0.001). Compared to controls, standardized mean difference with viscosupplementation ranged from 0.38 to 0.43 for knee pain and 0.32 to 0.34 for knee function (all P < 0.001). There were no statistically significant differences between viscosupplementation and controls for any safety outcome. They concluded that intra-articular injection of U.S.-approved viscosupplements is safe and efficacious through 26 weeks in patients with symptomatic knee OA. Limitations of this meta-analysis were significant heterogeneity in efficacy outcomes among included studies and smaller treatment effects in higher quality trials.³¹

Altman, et al. (2018) stated the evidence suggests HA has significant short-term efficacy (less than or equal to 6 months) for treating knee OA pain. While a single series of intra-articular HA has been well studied, the efficacy and safety of repeated courses of intra-articular HA injection therapy in knee OA patients have not been evaluated as frequently. They conducted a literature search using MEDLINE, EMBASE and PubMed databases. A total of 17 articles (RCTs and 10 cohort studies) met the pre-defined inclusion criteria. The inclusion criteria were (1) RCTs, (2) cohort studies with intra-articular HA as the primary treatment, (3) studies that provide at least 1 repeat course of intra-articular HA, (4) studies that measured knee pain as an outcome and (5) articles published in English. Studies ranged from investigating a single reinjection cycle to 4 repeat injection cycles. All studies reported pain reduction from baseline in the intra-articular HA treatment group throughout the initial treatment cycle, and either sustained or further reduced pain throughout the repeated courses of treatment. The study with the longest follow-up repeated intra-articular HA injection every 6 months for 25 months. Pain decreased after the first course and continued to decrease until the end of the study, with an approximate 55% reduction in pain compared to baseline. The authors concluded that repeated courses of intra-articular HA injections are an effective and safe treatment for knee OA. Repeat courses were demonstrated to maintain or further improve pain reduction while introducing no increased safety risk.⁵

The 2020 Department of Veteran Affairs/Department of Defense (VA/DoD) OA Clinical Practice Guidelines (CPG) Work Group decided upon a “Weak for” recommendation and suggest offering intra-articular viscosupplementation injection(s) for patients with persistent pain due to knee OA inadequately relieved by other interventions. Recent evidence comparing viscosupplementation injections to corticosteroid injections found that corticosteroid injections improved the short-term (1 month) VAS pain scores better than viscosupplementation injections, but that they are equivalent at 3 months, and viscosupplementation injections provided statistically significant improvement in VAS pain scores compared to corticosteroid injections at 6, 9, and 12 months. Further, they shared similar functional improvements in range of motion at 3 and 6 months and similar risk profiles.³²

The evidence reviewed for the use of HA injections for knee OA included SRs, meta-analyses, RCTs, retrospective observational studies, and evidence-based clinical practice guidelines from the AAOS, the ACR, the Arthritis Foundation, and the VA/DoD OA CPG Work Group. A literature review evaluating the strength of evidence supporting the efficacy and safety of intra-articular HA found that intra-articular HA provides a moderate symptomatic benefit for patients with knee OA without major safety concerns.⁴

The Evidence-Based Clinical Practice Guidelines from the AAOS concluded that viscosupplementation can represent a viable option for some patients that failed other treatments when appropriately indicated. HA intra-articular injection(s) is not recommended for routine use in the treatment of symptomatic knee OA.⁴ The HA recommendation was downgraded to Moderate Strength of recommendation due to lack of generalized results.²⁶

In numerous SRs, patients receiving HA experienced statistically significant improvements in pain, physical function, and overall disease symptoms compared with placebo. However, the magnitude of improvement varied across studies, and analyses with higher methodological quality, as well as more recent HA studies, have shown inconsistent results and less pronounced benefits.

Literature evaluating pain control and function concluded that intra-articular HA results in improvements in knee pain and function that can persist for up to 26 weeks in comparison with other treatment modalities.^6,27

The SR by the TAP concluded that trials enrolling older participants showed a small, statistically significant effect of HA on function and relatively few serious adverse events.²

The Evidence Based Guideline from the ACR and the Arthritis Foundation stated "a conditional recommendation against is consistent with the use of HA injections, in the context of shared decision making that recognizes the limited evidence of benefit of this treatment, when other alternatives have been exhausted or failed to provide satisfactory benefit."²⁵

Literature evaluating the efficacy and safety of repeated courses of intra-articular HA injection therapy in knee OA patients concluded that repeated courses of intra-articular HA injections are an effective and safe treatment for knee OA.⁵

The AMSSM recommends the use of HA for the appropriate patients with knee OA. “We RECOMMEND viscosupplementation injections for K-L grade ll-lll knee OA in those patients above the age of 60 years based on HIGH quality evidence demonstrating benefit using OMERACT-OARSI Responder Rating.” But the evidence should be downgraded because of indirectness for those younger than 60 years. “We SUGGEST viscosupplementation injections for knee OA for those under the age of 60 years based on MODERATE quality evidence due to response of treatment in those over 60 years of age.”³⁰

The VA/DoD OA CPG Work Group decided upon a “Weak for” recommendation and suggest offering intra-articular viscosupplementation injection(s) for patients with persistent pain due to knee OA inadequately relieved by other interventions.³²

Services performed for any given diagnosis must meet all of the indications and limitations stated in this LCD, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.

The patient’s medical record must contain documentation that fully supports the medical necessity for services included within this LCD.

The documentation must include the following:

1. Medical history and physical examination that supports symptomatic knee OA, and functional limitations.
2. X-ray report and/or notation in the medical record that confirms the diagnosis of knee OA.
3. Trial of conservative therapy, or failure, or contraindication to conservative therapy must be documented in the medical record.
4. Documentation must include whether 1 knee is being treated (which knee is being treated) OR both knees are being treated.
5. The frequency of injections and dosage given must be consistent with the FDA approved labeling and must be clearly documented.
6. Response to treatment must be noted.
7. If ultrasound is used for needle guidance with the joint injection, the documentation must support that the patient’s target site on the knee for needle placement may be difficult to access.
8. The procedure and related care are within the scope of practice of the physician or appropriately trained provider’s licensure.

Other Medicare Administrative Contractors (MACs) LCDs and Articles:

• Billing and Coding: Hyaluronic Acid Injections for Knee Osteoarthritis A59030
• Hyaluronic Acid Injections for Knee Osteoarthritis L39260

1. Bhadra AK, Altman R, Dasa V, et al. Appropriate use criteria for hyaluronic acid in the treatment of knee osteoarthritis in the United States. Cartilage. 2017;8(3):234-254.
2. Newberry SJ, Fitzgerald JD, Maglione MA, et al. Systematic Review for Effectiveness of Hyaluronic Acid in the Treatment of Severe Degenerative Joint Disease (DJD) of the Knee [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015 Jul 23. PMID: 26866204
3. Bannuru RR, Osani M, Vaysbrot EE, McAlindon TE. Comparative safety profile of hyaluronic acid products for knee osteoarthritis: A systematic review and network meta-analysis. Osteoarthritis and Cartilage. 2016;24(12):2022-2041.
4. Maheu E, Bannuru RR, Herrero-Beaumont G, Allali F, Bard H, Migliore A. Why we should definitely include intra-articular hyaluronic acid as a therapeutic option in the management of knee osteoarthritis: Results of an extensive critical literature review. Seminars in Arthritis and Rheumatism. 2019;48(4):563-572.
5. Altman R, Hackel J, Niazi F, Shaw P, Nicholls M. Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: A systematic review. Semin in Arthritis Rheum. 2018;48(2):168-175.
6. Campbell KA, Erickson BJ, Saltzman BM, et al. Is local viscosupplementation injection clinically superior to other therapies in the treatment of osteoarthritis of the knee: A systematic review of overlapping meta-analyses. Arthroscopy: The Journal of Arthroscopic and Related Surgery. 2015;31(10):2036-2045.
7. Cao Y, Cai R, Han S, et al. Quantitative analysis of the efficacy and associated factors of intra-articular hyaluronic acid with respect to osteoarthritis symptoms: A systematic review of randomized trials and model-based meta-analysis. Osteoarthritis Cartilage. Jun 2025;33(6):666-679. doi:10.1016/j.joca.2025.01.008
8. Migliorini F, Maffulli N, Simeone F, Jeyaraman N, Ramasubramanian S, Jeyaraman M. Intra-articular Hyaluronic Acid Injections May Be Beneficial in Patients with Less Advanced Knee Osteoarthritis: A Systematic Review of Randomised Controlled Trials. Sports Med. Aug 2025;55(8):1953-1969. doi:10.1007/s40279-025-02265-8
9. Sherman SL, Gudeman AS, Kelly JDt, Dimeff RJ, Farr J. Mechanisms of Action of Intra-articular Hyaluronic Acid Injections for Knee Osteoarthritis: A Targeted Review of the Literature. Am J Sports Med. Sep 2025;53(11):2771-2782. doi:10.1177/03635465241302820
10. Ferkel E, Manjoo A, Martins D, Bhandari M, Sethi P, Nicholls M. Intra-articular Hyaluronic Acid Treatments for Knee Osteoarthritis: A Systematic Review of Product Properties. Cartilage. 2023;14(4):424-432. doi:10.1177/19476035231154530
11. Pereira TV, Saadat P, Bobos P, et al. Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomized trials: A systematic review and network meta-analysis. Osteoarthritis Cartilage. Feb 2025;33(2):207-217. doi:10.1016/j.joca.2024.08.014
12. Bihlet AR, Henrotin Y, Lau EMC, et al. A single intra-articular injection of JTA-004, a combination of human plasma, hyaluronic acid, and clonidine, versus placebo in symptomatic knee osteoarthritis: A Phase 3 trial. Osteoarthritis Cartilage. Feb 2026;34(2):279-289. doi:10.1016/j.joca.2025.09.015
13. Chen CY, Lu CC, Liou IH, Huang MH, Ding RS, Sun SF. Efficacy and safety of a single intra-articular injection of mannitol-combined hyaluronan in patients with knee osteoarthritis - A double-blinded randomized clinical study. Knee. Jan 2026;58:104292. doi:10.1016/j.knee.2025.11.018
14. Küçükakkaş O, Aydin T, Yurdakul OV. Evaluation of the effect of intra-articular platelet-rich plasma and hyaluronic acid injections on femoral cartilage thickness in chronic knee osteoarthritis. Acta Orthop Belg. Dec 2022;88(4):811-819. doi:10.52628/88.4.10243
15. Ishijima M, Nakamura T, Shimizu K, et al. Different changes in the biomarker C-terminal telopeptides of type II collagen (CTX-II) following intra-articular injection of high molecular weight hyaluronic acid and oral non-steroidal anti-inflammatory drugs in patients with knee osteoarthritis: a multi-center randomized controlled study. Osteoarthritis Cartilage. Jun 2022;30(6):852-861. doi:10.1016/j.joca.2022.03.003
16. Yang C, Chen Q. Effects of ozone combined with articular injection of sodium hyaluronate on patients with knee osteoarthritis and their inflammatory factors and hemorheological indices. Afr Health Sci. 2023;23(2):360-366. doi:10.4314/ahs.v23i2.40
17. Bagheri K, Shekhar A, Kwok E, Dungy D, Stewart SL, Jamali AA. Platelet rich plasma compared to viscosupplementation in the treatment of knee osteoarthritis: A systematic review and meta-analysis of randomised controlled trials with 6 month and 12 month follow-up. J Exp Orthop. Jul 2025;12(3):e70335. doi:10.1002/jeo2.70335
18. Xu H, Shi W, Liu H, et al. Comparison of hyaluronic acid and platelet-rich plasma in knee osteoarthritis: a systematic review. BMC Musculoskelet Disord. Mar 11 2025;26(1):236. doi:10.1186/s12891-025-08474-6
19. Gupta N, Khatri K, Lakhani A, et al. Long-term effectiveness of intra-articular injectables in patients with knee osteoarthritis: a systematic review and Bayesian network meta-analysis. J Orthop Surg Res. Mar 3 2025;20(1):227. doi:10.1186/s13018-025-05574-w
20. Qiao X, Yan L, Feng Y, et al. Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis. BMC Musculoskelet Disord. Nov 30 2023;24(1):926. doi:10.1186/s12891-023-06925-6
21. Ivander G, Anggono Y. a comparison of intra-articular hyaluronic acid and platelet-rich plasma for knee osteoarthritis: a systematic review. Orthop Rev (Pavia). 2024;16:94236. doi:10.52965/001c.94236
22. Mekariya K, Manop P, Chernchujit B. Efficacy of single intra-articular 2% sodium hyaluronate versus corticosteroid injection in isolated patellofemoral osteoarthritis: A double-blind, randomized controlled trial. J isakos. Feb 2026;16:101038. doi:10.1016/j.jisako.2025.101038
23. Kim TW, Chang MJ, Shin CY, Chang CB, Kang SB. A randomized controlled trial for comparing efficacy and safety between intraarticular polynucleotide and hyaluronic acid for knee osteoarthritis treatment. Sci Rep. Jun 9 2023;13(1):9419. doi:10.1038/s41598-023-35982-z
24. Ghorbani O, Mahdibarzi D, Yousefi-Tooddeshki P. Comparison of the short-term effect of intra-articular hyaluronic acid and platelet-rich plasma injections in knee osteoarthritis: a randomized clinical trial. J Prev Med Hyg. Jun 2024;65(2):E214-e220. doi:10.15167/2421-4248/jpmh2024.65.2.3270
25. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Rheumatol. 2020;72(2):220-233.
26. The American Academy of Orthopaedic Surgeons. Management of Osteoarthritis of the Knee (Non-Arthroplasty): Evidence-Based Clinical Practice Guideline. 2021.
27. Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: A systematic review and network meta-analysis. Ann Intern Med. 2015;162:46-54.
28. Berkoff DJ, Miller LE, Block JE. Clinical utility of ultrasound guidance for intra-articular knee injections: A review. Clinical Interventions in Aging. 2012;7:89-95.
29. Ong KL, Anderson AF, Niazi F, Fierlinger AL, Kurtz SM, Altman RD. Hyaluronic acid injections in Medicare knee osteoarthritis patients are associated with longer time to knee arthroplasty. The Journal of Arthroplasty. 2016;31:1667-1673.
30. Trojian TH, Concoff AL, Joy SM, Hatzenbuehler JR, Saulsberry WJ, Coleman CI. AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthritis: Importance for individual patient outcomes. Clin J Sport Med. 2016;26(1):1-11.
31. Strand V, McIntyre LF, Beach WR, Miller LE, Block JE. Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: A systematic review and meta-analysis of randomized, saline-controlled trials. Journal of Pain Research. 2015;8:217-228.
32. The Non-Surgical Management of Hip & Knee Osteoarthritis Work Group. VA/DoD Clinical Practice Guideline for the Non-Surgical Management of Hip and Knee Osteoarthritis. 2020.

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