An overview of knee osteoarthritis treatments.

Marc Darrow, MD. JD.

There are many ways to treat knee osteoarthritis. Some successful, other not. As each person represents a unique case, it is difficult top determine which treatment would be best for an individual. When I started this work in regenerative medicine more than 25 years ago, the options were mainly surgery or painkiller. But that was then, with the advent of “biomedicine” (blood and stem cell therapies), the choices have changed dramatically.

From this point of view, arthroscopic surgery is now seen as the least desirable option, and knee replacement something that should be delayed as long as possible. The repair and stimulation of cartilage and damaged or worn tissue growth is now seen as the most desirable option.

In the decades of the 20th century and the decades of the 21st century, studies on cell regeneration therapies for soft tissue and cartilage repair began to be published at an amazing rate. The reason for this explosion in research is simple: doctors and patients are seeing poor results from surgery, along with unexpected side effects, and the powerful new tools of biomedicine are thus becoming a major focus.

Before biomedicine and the understanding of how stem cells and blood platelets could be used in orthopedic medicine,, the gold standard of treatment for patients suffering from debilitating joint pain due to a “bone-on-bone” condition was joint replacement. However, as the decades progressed, patients who had received replacement therapy grew older, and their prosthetic joints began to wear out.

Doctors became aware of a new challenge for themselves and their patients, one that did not have an easy solution. In older joint replacements, bone was removed and replaced with metal. When a revision (second) replacement was needed, some patients no longer had enough bone to have this surgery. These patients’ knees, shoulders, and hips became “salvage” jobs, as doctors tried to do what they could with whatever was left of the original joint. During my internship, after a patient’s surgical hip joint replacement failure, I assisted my mentor in carving an entire femur from a cadaver, and placing it into the pelvis and knee to create new joints. The chance for success was minimal, but at least amputation was postponed—for good or bad, I am not sure.

Do people really have bone on bone knees?

An overview of knee osteoarthritis treatments should begin with the accuracy of the knee osteoarthritis diagnosis. Options to surgery are usually not discussed with patients should they have an MRI which demonstrates “bone on bone.” Many of our patients present with a diagnosis of “bone-on-bone knee arthritis,” terminology used to describe a knee that has lost all cartilage to cushion the bones. Few actually have true “bone on bone.”

If the joint moves, there is typically cartilage present since cartilage is the slippery surface on the end of the bones that allow range of motion. When the doctor says you have bone-on-bone arthritis, it may be used as an umbrella term to describe various levels of knee degeneration. In the knee joint, cartilage covers the tibia, femur, and the back of the kneecap (the patella); in addition to cartilage, there is the meniscus, which is the fibrous padding between the bones. A healthy knee glides efficiently and painlessly on these structures.

Bone-on-bone can mean that some or all of the cartilage and/or the meniscus have worn down or have defects, thereby causing the bones to rub together. Another diagnostic term that may refer to bone-on-bone is “osteochondral defect.” The term “osteochondral” refers to the cartilage and bone as a unit.

Patients often assume that bone-on-bone or an osteochondral defect means extreme and advanced cartilage deterioration, which is not usually the case. Joint space, the space between the bones, is a challenge to surgeons. If there is no space between the bones, i.e, the cartilage has worn down—surgery cannot restore it. The philosophy then is to manage the knee pain as long as possible (often with repeated steroid injections that temporarily reduce pain, but eventually destroy whatever cartilage is left) prior to the knee replacement surgery.

A brief discussion on MRI readings 

I often receive emails from prospective patients who have an X-ray or MRI they want to send us. Sometimes they want an opinion to back up a surgical recommendation; sometimes they want an opinion to support their desire to avoid surgery. In either case, when I tell them that the X-ray or MRI may not be telling the truth about their pain source, they become surprised and confused. New findings say that many MRIs are useless. Investigators examined patients who had had an MRI for knee pain to determine whether the MRI was helpful in determining the final outcome of treatment. I ask you to refer to my article How accurate are MRI scans of the knee? For a detailed discussion.

Treatments for Knee osteoarthritis: Total Knee replacement

While knee replacement can sometimes be a viable and effective treatment for patients with knee osteoarthritis, the number of patients asking about knee replacement alternatives continues to grow. Patients need to be aware of the potential downsides of the procedure, particularly in light of the new therapies available.

Over the years I have seen many patients who still had knee pain following knee replacement surgery. What I see in my practice agrees with what medical research states—that knee replacement surgery offers hope to some patients, and these patients have high expectations of what the new knee will offer them, but that in many cases those expectations are not met.

English doctors wrote in a June 2022 study (1) that up to 20% of people who undergo total knee replacement surgery have ongoing pain and discomfort. The researchers write: 

  • Patients describing chronic postsurgical pain also “described sensations of discomfort, including heaviness, numbness, pressure, and tightness associated with the prosthesis.
  • Participants reported “a lack of felt connection with and agency over their replaced knee, often describing it as alien or other, and lacked confidence in the knee.”

Research: Realistically 9 to 30% of patients do not return to work after knee replacement

In my article: How fast can you get back to work or sport following knee replacement? I refer to studies which suggest that some patients have an over-expectation of what their knee replacement will do for them. Their doctors are concerned that people have a limited understanding of the realistic variables that determine the ability to return to work. In other words – they think they can get back to work sooner than they will actually be able to. As the research of this article shows 9 – 30% of people who have knee replacement, do not return to work.

In my article Do Women Have More Knee Replacement Complications? I discuss research which suggests that in the postoperative period, women, happy that they had the knee replacement lost motivation and confidence in the post-surgery recover.  This may help explain, as I cite in the research why women appear to have worse outcomes, more pain, and poorer functional outcomes following total knee replacement than men and what may have caused these outcomes. The research suggests that women  had significantly worse pre-surgery pain, limited function, depression, were more likely to be obese, and had pain in more than four joints. 

Other factors discussed were knee replacement complications from weak bones in postmenopausal women. The connection of osteoporosis and osteoarthritis commonly coexist in postmenopausal females can be sometimes lost.

Knee Replacement Failure

There are many studies connecting weight and knee replacement failure. Many total knee replacement patients are overweight or obese. There is a thinking among many that after the knee replacement, their  physical activity levels and weight will improve. This does not appear to be true for some as research points out. In many knee replacement patients, weight loss does not occur. In my article Research: Knee replacements do not help you lose weight, I discuss many of these studies patients suffered from knee pain, loss of knee function, swelling, and an inability to walk or stand for any length of time, but thought that knee replacement would help restore their activities and thereby they could lose weight. For many people, this is not what happens, research cited in my article shows “the majority of total knee replacement patients are overweight or obese and physical activity levels and weight do not appear to change in a high proportion of patients after knee replacement.”

Knee replacement survival rate in middle-aged patients up to 65 years old

An April 2023 paper in the journal Cartilage (29) documented the knee replacement survival rate in middle-aged patients up to 65 years old and to compare it with other age groups of patients undergoing total knee replacement for knee osteoarthritis. Over 45,000 patients were in this study.

Learning points:

  • A total of 45,488 total knee replacement patients for primary knee osteoarthritis were included in the analysis. Of this there were 11,388 men and over twice as many women: The number of women was 27,846).
  • The percentage of knee replacement patients less than 65 years old increased from 13.5% to 24.8% between 2000 and 2019. (Many more knee replacements (increases) in this group.)
  • The survival analysis showed an overall influence of age on the implant revision rate.
    • Patients under 50 years old estimated survival rate of 78.7% at 15 years (revision knee surgery or other procedure will need to be done at age 65 for over 20% of patients)
    • Patients 50-65 years estimated survival rate of 89.4% at 15 years (revision knee surgery or other procedure will need to be done at age 65 to age 80 for over 10% of patients)
    • Patients 66-79 years estimated survival rate of 94.8% at 15 years.

Conclusions: “Total knee replacement us in the middle-aged patient population up to 65 years old increased significantly over time. These patients present a double risk of failure with respect to older patients. This is particularly important considering the increasing life expectancy and the emergence of new joint preserving strategies (including knee injections), which could postpone the need for total knee replacement to an older age.

Does having bowlegged knee osteoarthritis or knock knee knee osteoarthritis make a difference in treatments?

In an April 2023 study (2), doctors examined the medical histories of 834 people to see if people with bowlegged knee osteoarthritis or knock knee knee osteoarthritis patients could avoid knee replacement surgery with conservative care treatments. The researchers looked at patients with advanced knee osteoarthritis, Kellgren-Lawrence knee osteoarthritis grades III and IV. These patients were divided into varus arthritic bow-legged knee (bow-legged) or valgus arthritic knee, knock-knees.  They found that the valgus arthritic knees responded better to conservative treatment than varus arthritic knees and had less chance of needing knee replacement. Five years after the start of conservative care treatments 76.8% of varus – bow legged patients needed knee replacement while 38.6% of valgus arthritic knee patients went on to knee replacement.

In this image, the man has varus arthritic knees, more commonly known as being “bow-legged.” Bow legged people are at higher risk for needing knee replacement.

varus arthritic knees

Treatments for Knee osteoarthritis: Anti-inflammatories and painkillers

Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences.

A study from 2022 (3) writes about the need for new knee pain treatments: “Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee osteoarthritis has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, none of them has articular cartilage regenerating potential. . .(in this paper the researchers) focus on emerging osteoarthritis knee treatments, relieving symptoms, and regenerating damaged articular cartilage that includes intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), metformin, lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC),” and other treatments. We will be discussing some of these treatments in this article and the research published by other investigators.

Irenka and Cymbalta

A May 2022 paper (4) from Dutch researchers assessed the effectiveness of duloxetine (Irenka and Cymbalta) in addition to usual care in patients with chronic osteoarthritis pain. Patients with chronic hip or knee osteoarthritis pain who had an insufficient response to acetaminophen and nonsteroidal anti-inflammatory drugs were included. Patients received duloxetine (60 mg/day) in addition to usual care or usual care alone.

  • A total of 66 patients were randomized to receive duloxetine in addition to usual care, and 66 patients were randomized to receive usual care alone.
  • No difference in pain scores between the groups at 3 months or at 12 months.
  • Conclusion: Researchers found no effect of duloxetine added to usual care compared to usual care alone in patients with chronic knee or hip osteoarthritis pain.

Treatments for Knee osteoarthritis: Weight loss

In my article Weight loss can be a knee replacement alternative treatment, I write that “People who are overweight understand that their arthritis related knee problems can be made worse because of their weight.” Research cited in the article describes how small reductions in body weight can decrease osteoarthritic knee pain and thus should provide a strong incentive for weight-loss. Highlights of that research is a Wake Forrest study which found for every 1 pound of weight loss, there is a 4-pound reduction in knee-joint load per step. Numerous studies have suggested that the magnitude of 10 pounds of weight loss would be a significant reduction in osteoarthritis risk and knee pain.

Weight loss saves a meniscus

A recent study concluded that overweight and obese people who lost a substantial amount of weight over a 48-month period showed significantly lower degeneration of their knee cartilage.

A July 2022 study (5) examined the recommended non-surgical interventions for osteoarthritis including weight loss plus exercise.

  • Nine knee osteoarthritis studies, evaluating diet plus exercise, exercise, unloading shoes, high-expectation communication during acupuncture and telephone-based weight loss plus exercise were identified.
  • In knee osteoarthritis, some evidence suggests that the benefits of:
    • diet and exercise are mediated through changes in body weight, systemic inflammation and self-efficacy;
    • exercise is mediated through changes in knee muscle strength and self-efficacy; and
    • high-expectation communication style is mediated through changes in self-efficacy.

Exercise for knee osteoarthritis

A June 2023 study (6) looked to identify the most effective type of exercise therapy for knee osteoarthritis with regard to pain, stiffness, joint function, and quality of life. To achieve the study’s goal, researchers looked at thirty-nine previously published studies in the medical literature and compiled results. In the end five five different exercise therapy groups:

  • aquatic exercise,
  • stationary cycling,
  • resistance training,
  • traditional exercise
  • and yoga

Outcomes among the groups were assessed with the:

  • Western Ontario and McMaster University Osteoarthritis Index (WOMAC),
  • 6-minute walk test
  • visual analog scale (VAS) for pain, and
  • Knee injury and Osteoarthritis Outcome Score (KOOS);

A total of 2646 participants were included.


  • Significantly worse WOMAC-Pain scores were seen in controls compared with all exercise interventions except aquatic exercise
  • Worse scores were seen in controls compared with Yoga regarding WOMAC-Stiffness and WOMAC-Function
  • Stationary cycling was the most effective for improving WOMAC-Pain and 6-minute walk test.
  • Yoga was most effective for improving WOMAC-Stiffness, WOMAC-Function, Knee injury and Osteoarthritis Outcome Score-Activities of Daily Living, and KOOS-Quality of Life (79.1%)
  • Aquatic exercise, was the most effective regarding VAS pain and Knee injury and Osteoarthritis Outcome Score-Pain; and resistance training was the most effective regarding Knee injury and Osteoarthritis Outcome Score-Symptoms.

Conclusion: All 5 types of exercise were able to ameliorate knee osteoarthritis.

Treatments for Knee osteoarthritis: Acupuncture


When going through the medical research one can find many positive studies regarding pain alleviation in patients treated with acupuncture. Other research however points out that much of these positive outcomes should be understood in the terms of bias. While many studies cite the benefits of treatment a January 2022 paper however (7)  did not. The researcher here wrote: “At short-term, there was low to very low evidence and there were statistically significant differences in pain intensity and knee function in favor of acupuncture versus control interventions in patients with knee osteoarthritis. A July 2019 study (8) demonstrated this by saying: “According to the high-quality evidence, we concluded that acupuncture may have some advantages in treating knee osteoarthritis. However, there are some risk of bias and reporting deficiencies still needed to be improved.” In other words, the evidence was not reliable.”

A December 2023 paper (9)  examined how effective acupuncture and knee exercises may be for some patients in improving pain and function of knee osteoarthritis. The researchers reviewed the records of 774 knee osteoarthritis patients taken from 11 high-quality studies.

The results showed that acupuncture combined with active exercise training (combined group) was superior to the acupuncture group in improving the total effective rate, reducing the pain level, improving knee joint function, and improving joint range of motion.

Please refer to my article Does acupuncture help knee osteoarthritis?

Treatments for Knee osteoarthritis: Cortisone injections

We  see many patients who have concerns about prolonged cortisone injections. Most recently we have been seeing many patients concerned about frequent recommendations to cortisone while they wait for knee surgery. Initially their doctors advised them that cortisone injections  can be effective and safe if used in moderation or as a one time treatment. But as this knee replacement recommended patient continued to wait for a surgery during and after the pandemic and surgical cases significantly back-logged, decisions had to be made as to how cortisone could be used to provide comfort until the surgical date. This was a difficult question for doctors to answer. A number of new research studies began to appear to try to offer medical professionals some basis for continued cortisone use.

A September 2021 paper (10) found: “There are growing concerns with the widely used glucocorticoids during the Coronavirus disease-19 (COVID-19) pandemic due to the associated immunosuppressive effects, which may increase the risk of COVID-19 infection and worsen COVID-19 patient outcome. Heavily affecting orthopedics (elective joint and spine surgeries), the pandemic led to delay and cancellation of almost all surgical cases, and procedures including perioperative intra-articular corticosteroid injections  saw similar decreases. However, the benefits of intra-articular corticosteroid injections treatments during the pandemic may outweigh these potential risks, and their continued use may be warranted.”

I have numerous articles on this website on cortisone injections. I invited you to review the material and the research presented here.

Ultrasound-guided genicular nerve blocks

July 2022 study: (11) “Ultrasound-guided genicular nerve blocks using pharmacological agents for pain control in chronic knee osteoarthritis are gaining in popularity. There is fair evidence to at least target the superior medial genicular nerve, inferior medial genicular nerve, and Inferior medial genicular nerve using local anesthetics, corticosteroids, or alcohol to reduce pain and to improve knee function in patients with chronic knee osteoarthritis under ultrasound guidance. The procedure is safe but more research is needed to determine the optimal interventional approach.”

A September 2022 (12) paper describes Genicular nerve ablation (GNA) as a percutaneous, needle-based therapy option designed to palliatively treat knee pain. Analogous to an intra-articular injection with corticosteroid, GNA is not intended to remedy the root cause of pain or structurally alter the joint in any way; rather, the goal is to block/interrupt the transmission of pain signals from the knee, itself, thus eliminating the perception of pain by the brain. 

Treatments for Knee osteoarthritis: Hyaluronic acid injections

I have seen patients require incision and drainage with antibiotic treatment after experiencing allergic reactions to hyaluronic acid injections. When the injections are mistakenly placed into the soft tissue instead of the joint, severe reactions can occur. Studies have confirmed that when knee injections are made blindly—that is, without ultrasound guidance—one-third of the injections do not enter the joint. Unfortunately, most doctors do not inject under ultrasound guidance.

Treatments for Knee osteoarthritis: Botox injections

A March 2023 (13) study investigated the effectiveness and safety of intra-articular Botulinum Toxin type A injection in the management of patients with knee osteoarthritis. Seven random control trials comprising 548 participants were included in this meta-analysis. The researchers found compared with the control group, Botulinum Toxin type A injection exhibited greater pain reduction at 4 weeks post-treatment but not 8-24 weeks post-treatment.

Placebos can improve symptoms in various medical conditions including knee pain

May 2022 study (14) Recent studies indicate that the administration of open-label placebos  can improve symptoms in various medical conditions. The primary aim of this 3-week randomized controlled trial was to examine the effects of open-label placebos  treatments on pain, functional disability, and mobility in patients with arthritic knee pain. Evaluation of daily pain ratings indicated significant pain decrease in the open-label placebos  groups compared to no treatment group.  open-label placebos treatment improved knee pain in elderly patients with symptomatic knee osteoarthritis (OA), while functional disability and mobility of the knee did not change. The content of the verbal suggestion was of minor importance. open-label placebos administration may be considered as supportive analgesic treatment in elderly patients with symptomatic knee osteoarthritis.

Calming landscapes and scenes in virtual reality as a clinical treatment for older adults with chronic osteoarthritis knee pain

A June 2022 study (15) “There is an urgent need for safe and effective nonpharmacologic approaches to treat chronic knee pain in older adults. Although virtual reality (VR) has shown some effectiveness for acute pain, there is limited evidence on the effects of virtual reality on chronic pain particularly with older adult populations. This study evaluated the feasibility and effectiveness of virtual reality as a clinical treatment for older adults with chronic osteoarthritis knee pain.

  • Nineteen participants aged 60+ years old participated in a 10-min virtual reality meditation program. Results suggest that virtual reality meditation had significant moderate to large analgesic effects on knee pain intensity, primarily during virtual reality and post virtual reality, with some lasting effects into next day. The findings also suggest virtual reality meditation intervention had a positive effect on affect, with a significant large decrease in negative affect scores pre- to post-virtual reality. The significant moderate to large decreases in pain interference for normal work, mood, sleep, and enjoyment of life suggest that older adults may have a higher ability to participate in meaningful daily activities up to 24-48 hours after virtual reality meditation. VR appears to be a feasible and effective nonpharmacological tool for older adults to treat chronic overall and knee-specific pain.

In a June 2022 study (16) Doctors investigated the incidence and risk of knee and hip replacement in patients with osteoarthritis treated with different medications. Compared to non-users, bisphosphonate users had a reduced risk of knee replacement.

Regenerative medicine treatments for degenerative knee disease

An August 2021 paper (17) described the various regenerative medicine treatments for degenerative knee disease. “Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the knee, including symptomatic osteoarthritis and chondral injuries, as well as injuries to tendon, meniscus, and ligament, including the anterior cruciate ligament. Promising and established treatment modalities include hyaluronic acid in liquid or scaffold form; platelet-rich plasma (PRP); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs), hematopoietic stem cells, endothelial progenitor cells, and growth factors; connective tissue progenitor cells (CTPs) including adipose-derived mesenchymal stem cells (AD-MSCs) and tendon-derived stem cells (TDSCs); matrix cell-based therapy including autologous chondrocytes or allograft; vitamin D; and fibrin clot.”

Non-surgical knee osteoarthritis treatments: Stem cell therapy


It became clear to many researchers that joint replacement had to be redefined and disputed as the gold standard of treatment. Others, however, had already decided to abandon joint replacement and explore growing tissue as the new standard of care. The thinking was simple—why remove bone and tissue when these could be repaired and rejuvenated?

What was found in the initial research was startling. Doctors discovered that one type of stem cell (mesenchymal stem cells found in bone marrow and body fat) could morph into bone cells and cartilage cells when injected into a joint. The ramifications for the treatment of osteoarthritis or “bone-on-bone” joints were enormous. Stem cell injections showed that cartilage could be regrown, something that doctors had previously thought impossible because of the  cartilage’s limited blood supply within the joint.

An October 2022 paper (18) writes: “In knee osteoarthritis, most of the evidence for mesenchymal stem cells comes from case series and small, randomized trials. Overall, there were improvements in pain and functional outcomes when patients were treated with mesenchymal stem cells, and the results suggest that mesenchymal stem cells found in bone marrow can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions.”

A September 2023 paper (28) assessed the impact of a patient’s body mass index, his/her severity of knee osteoarthritis, age and gender to see if these factors have any influence on the final clinical results of bone marrow aspirate concentrate injection. In this study 111 patients with painful knee osteoarthritis had bone marrow aspirate concentrate (BMAC) therapy. They were then followed up for a year. The study team suggested the biggest impact on outcomes came from severity of the knee osteoarthritis. “Significant pain and functional improvement were observed in all participant groups. Participants’ age and BMI did not influence the clinical outcome, but there was an influence of osteoarthritis severity, especially among older patients.”

Non-surgical knee osteoarthritis treatments: Platelet Rich Plasma therapy

  • PRP treatments involve collecting a small amount of your blood and spinning it in a centrifuge to separate the platelets from the red cells. The collected platelets are then injected back into the injured area to stimulate healing and regeneration.
  • The platelets contain healing agents, or “growth factors.” including Platelet-derived growth factor (PDGF), Transforming growth factor beta (or TGF-β, Insulin-like growth factors, Vascular endothelial growth factor (VEGF) and Epidermal growth factors.
  • The number of treatments needed can vary from patient to patient depending on the level of knee degeneration and the level of activity the patient wishes to return to.

PRP injections are considered controversial by some, mostly because of the lack of standardization in the preparation and administering of this treatment. I address these studies and commentaries in my article Platelet Rich Plasma injections for knee osteoarthritis. A January 2023 paper (19) also addressed these issues by writing: “The use of platelet-rich plasma (PRP) has been supported by encouraging data from in vitro and preclinical in vivo studies, both in terms of safety and efficacy. This led to the wide use of PRP injections in the clinical practice, with promising results especially as a minimally invasive treatment for cartilage degeneration and osteoarthritis. While many controversies remain on the best PRP formulation, the overall available clinical studies support the benefits of PRP, with functional improvement and reduction of pain-related symptoms up to 12 months, especially in young patients and early osteoarthritis stages.”

Non-surgical knee osteoarthritis treatments: Prolotherapy

Prolotherapy is the injection, often dextrose (a simple sugar), into the knee. Prolotherapy, which is short for “proliferation therapy” (the proliferation of new cells following the injection of a substance that will stimulate new tissue growth). Prolotherapy is injected into the knee or other area, it causes the body’s immune system to stimulate the inflammatory process. This new inflammatory response attracts fibroblasts (immature cells present in connective tissue) and chondrocytes (cells that produce cartilage) and brings them to the area of degeneration or injury. These cells rebuild the collagen (more specifically, what is called the “collagen matrix” of the tissue) and enable it to strengthen and restore the body part in many cases to pre-injury status.

There is a long history of medical studies on the effectiveness of Prolotherapy for knee pain.

Prolotherapy compared to Hyaluronic injections

In a September 2022 study researchers compared the effectiveness of dextrose Prolotherapy injections to hyaluronic acid injections in knee osteoarthritis patients. The researchers reported that initially there was no statistically significant differences recorded in short-term effectiveness found between prolotherapy and hyaluronic acid treatments in pain control, however, in the subanalysis that included only the studies that used intra-articular injections, prolotherapy was found to be more effective a treatment.

Prolotherapy, Platelet Rich Plasma Injections and exercise therapy

In a September 2022 study researchers demonstrated the effectiveness of Platelet Rich Plasma and dextrose Prolotherapy treatments in knee osteoarthritis. The study suggested: “Pain and disability were significantly improved with prolotherapy and PRP compared with exercise therapy.

Non-surgical knee osteoarthritis treatments: Alpha-2-macroglobulin (A2M)

Alpha-2-macroglobulin (A2M), is a a naturally occurring macromolecule, a protein, that exhibits anti-inflammatory properties. A 2020 study (20) compared one injection of A2M, cortisone and PRP for effectiveness in knee osteoarthritis. At 12 weeks after the injection the study doctors found Alpha 2 Macroglobulin injections showed similar effectiveness to corticosteroids in the treatment of knee osteoarthritis. Both A2M and corticosteroids appear to show marginally better effectiveness than PRP injection, however the differences are small and did not reach statistical significance in most outcome measures.

Dry Needling

A January 2023 study (21) examined the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with knee osteoarthritis.

This “randomized, single-blinded, clinical trial” was carried out for 6 weeks of treatment and 6-month follow-up.

  • A group of 98 patients were randomly divided into two groups.
    • Group 1 received dry needling at latent and active myofascial trigger point and stretching exercises
    • Group 2 received oral diclofenac with stretching.
    • Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up.

Results: A total of 42 patients in the dry needling group and 35 patients in the diclofenac group completed the study, “there was no significant difference in the general data between the two groups.” The researchers added: “After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the dry needling group showed a significantly better result than the diclofenac group. Especially in the results of the 6-month follow-up, the dry needling group showed much better results than the the diclofenac group.”

The researchers conclusion: “Dry needling on latent and active myofascial trigger points combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by knee osteoarthritis. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months.”

Tumeric, curcumin

A November 2023 paper (22) examined if curcumin therapy was effective for knee osteoarthritis. As explained in this paper, “Curcumin, a polyphenolic compound extracted from turmeric, is widely used in traditional Chinese medicine to treat osteoarthritis and rheumatoid arthritis.” The study researchers compiled data from 23 studies from 7 countries, including 2175 knee osteoarthritis patients and 6 interventions. Results showed that compared with placebo, curcumin significantly reduced the visual analogue scale pain score and total WOMAC score.

The researchers also suggested as “compared with placebo, curcumin, curcumin + NSAIDs, and NSAIDs reduced the use of rescue medication. Compared with NSAIDs, curcumin, and curcumin + NSAIDs had a reduced incidence of adverse reactions.”

The paper concludes: “Curcumin, either alone or in combination with other treatments, is considered to have good clinical efficacy and safety in knee osteoarthritis treatment. Drug combinations containing curcumin may have the dual effect of enhancing efficacy and reducing adverse reactions, but this possibility still needs to be confirmed by further clinical and basic research.”


A November 2014 study (24) undertook to provide a better understanding between the zinc and iron intake and the advancement of subchondral (bone thickening) sclerosis among patients with osteoarthritis. The goal of the researchers was to “establish personalized, nutritionally-informed strategies designed to retard the progression of subchondral sclerosis and conserve joint structure.” Four hundred and seventy four patients compromised the study group (216 females, 258 males, average age about 64 years old.)

The researchers found a positive association between elevated zinc intake and a slowdown in the progression of subchondral sclerosis in osteoarthritis patients, notably among females, middle-aged individuals, and those with higher calcium and magnesium intake. Conversely, a higher iron intake might intensify subchondral sclerosis.

Oral cannabidiol CBD

A November 2023 study (23) examined the use of oral cannabidiol as add-on to paracetamol for painful chronic osteoarthritis of the knee. In this study, the researchers investigated the effects of oral high-dose CBD administered over 8 weeks on pain, function and patient global assessment as an add-on to continued paracetamol in chronic symptomatic knee osteoarthritis.

In this study, participants were on continued on a dosage of paracetamol 3 g a day and randomly assigned to oral cannabidiol 600 mg/d (43 patients) or placebo (43 patients). The researchers were looking for a change in WOMAC pain subscale scores (0 = no pain, 10 = worst possible pain) from baseline to week 8 of treatment. The researchers did not find any difference in pain between the CBD and the placebo group. They write: “In knee osteoarthritis patients, oral high-dose add-on cannabidiol had no additional analgesic effect compared to adding placebo to continued paracetamol. Our results do not support the use of cannabidiol as an analgesic supplement in knee osteoarthritis.”

Vitamin D levels should be monitored

An October 2023 paper (25)  investigated the relationship between vitamin D status, age, body mass index (BMI), and knee osteoarthritis in a group of individuals in Saudi Arabia. The study included 93 participants with suspected knee osteoarthritis, of which a substantial portion of the sample population presented with knee osteoarthritis.

  • Obesity was a prevalent factor among knee osteoarthritis patients, with grade 2 (18.3%) and grade 3 (25.8%) being the most frequent.
  • Vitamin D deficiency was prevalent in 54 (58%) of patients.
  • Among knee osteoarthritis cases, bilateral involvement was predominant in 46 (79%), with a substantial portion, 36 (62%), presenting deficient vitamin D levels.

Vitamin D levels should be monitored: The researchers of the study concluded:

“The findings from this study highlight the importance of monitoring and maintaining adequate vitamin D levels to potentially reduce the risk of knee osteoarthritis and the need for early detection and intervention to manage knee osteoarthritis, particularly in females, older population, and obese adults. ”

A September 2023 paper (26) tested the effects of vitamin D supplementation compared to placebo over 5 years in patients suffering with knee osteoarthritis. What they found was that vitamin D did niot help patients, especially those who had a prior knee surgery. They did however suggest that among the patients in the study who had no prior knee surgery, “2-year vitamin D supplementation and maintaining sufficient vitamin D was linked to modest improvements in knee symptoms and depression scores in knee osteoarthritis.”

An August 2023 analysis (27) of eight previously published studies suggested that vitamin D was beneficial in slowing down the progression of the synovial fluid volume (reducing swelling, pain, stiffness), improving the subjective pain and function of the patients and reducing the tibial cartilage degeneration.


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