Alternatives to knee replacement: Conservative care of knee osteoarthritis

Marc Darrow, MD. JD.

Many patients we see, present with a diagnosis of “bone-on-bone 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. 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.

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.

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.

We 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.

“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 (2) 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.

A March 2024 study (3) examined the long-term impact of non-steroidal anti-inflammatory drugs (NSAIDs) on the progression of symptoms and structural deterioration of the joint in knee osteoarthritis. The study analyzes data from 4197 participants (8394 knees) over 4-to-5 years. The study found that, relative to non-users, individuals using NSAIDs long-term were significantly more likely to experience aggravated symptoms exceeding the minimally clinically important difference, specifically, pain, disability, and stiffness.

Long-term users also faced a higher probability than non-users of having total knee replacement . These findings suggest that long-term NSAID use could accelerate the progression to total knee replacement by markedly exacerbating symptoms.

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.

A September 2024 study (5) reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged over 65 years).

• Fifteen studies (1369 participants) with the most frequently studied antidepressants being duloxetine and amitriptyline (6/15 studies each).
• For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0-2 weeks), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (more than 6 weeks and less than 12 months).

However, the study concludes: “For most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of less than 100 patients, have disclosed industry ties and classified as having unclear or high risk of bias.”

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 (6) 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.

Very Low-Calorie Ketogenic Diet

A September 2024 study (7) looked at women with symptomatic knee osteoarthritis and obesity and monitored a Very Low-Calorie Ketogenic Diet in these patients. Here are the observations:

• Twenty participants started the study, but four discontinued the diet, with two of these being due to adverse effects.
• The mean age of the 16 patients who completed the 20-week program was about 57 years old, and their average Body Mass Index was 40.0 (Class 3: severe obesity).
  • The average BMI significantly decreased to 37.5 (Class 2 obesity at week 4), 36.3 (Class 2 obesity at week 8), and 34.8 (Class 1 obesity at week 20).
  • Self-reported pain and function scores showed that weight loss significantly reduced pain and increased function.

A December 2024 paper (8) studied low muscle mass index and sarcopenic obesity (muscle loss and obesity) with knee osteoarthritis. The researchers write: “In reviewing previously published data of 12 studies, low-quality evidence indicated that low muscle mass index and sarcopenic obesity increase the odds of knee osteoarthritis. However, no association was observed between general sarcopenia or low muscle mass with knee osteoarthritis.”

Do fatty acids protect against knee osteoarthritis? Study says no.

A June 2024 study (9) suggests that although n-3 (omega-3) fatty acids may reduce inflammation, different n-3 (omega-3) fatty acids have different effects on inflammation and clinical outcomes, with eicosapentaenoic acid (EPA) having the strongest effect, there is a question as to how much impact, good or bad, specific essential fatty acid levels have on the development of osteoarthritis.

A multi-university study lead by Boston University studied 363 cases with incident symptomatic knee osteoarthritis and 295 with incident radiographic knee osteoarthritis. Results for other osteoarthritis outcomes also failed to suggest a protective effect of specific n-3 fatty acids with osteoarthritis outcomes.

A June 2023 study (10) 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.

Results:

• 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.

• A May 2024 review study (11) of 756 knee osteoarthritis patients indicated that compared to the control group, Yoga exercise showed significant improvements in alleviating pain, stiffness, and physical function among knee osteoarthritis patients. However, there was no significant improvement observed in terms of activities of activity of daily living and quality of life. The study concludes: “In general, Yoga has been found to be effective in reducing pain and stiffness in knee pain patients, it can also improve the physical function of patients. However, there is limited evidence to suggest significant improvements in terms of activity of daily living and quality of life.”

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 (12)  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 (13) 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 (14)  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.

A July 2024 paper (42) investigated longer-term effectiveness of acupuncture. In this review study 10 randomized controlled trials involving 3221 participants were included. Pooled estimates suggested that acupuncture may offer potential improvements in function and overall pain for 4.5 months post-treatment versus sham acupuncture. Acupuncture may provide durable clinically important pain relief and functional improvement up to 5 months post-treatment versus usual care, and up to 6 months post-treatment versus diclofenac (NSAIDs).

Please refer to my article Does acupuncture help knee osteoarthritis?

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.

An example of prolonged cortisone treatments. 

The COVID pandemic created numerous unwanted situations including the prolonged use of cortisone when surgeries were not available. A September 2021 paper (15) 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.”

An August 2022 study (16) wrote: “Recent findings have demonstrated that intraarticular glucocorticoid injections can be deleterious (harmful) for knees with osteoarthritis. This study was undertaken to assess, in a real-life setting, the risk of knee osteoarthritis progression in patients who received intraarticular glucocorticoid injections over a 5-year follow-up period. the researchers found intraarticular glucocorticoid injections for symptomatic knee osteoarthritis did not significantly increase the 5-year risk of incident total knee replacement or radiographic worsening (MRI showing continued knee degrading). However, the researchers added these findings should be interpreted cautiously.

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

• How much cortisone can I get in my knee? Are there alternatives to cortisone?
• Systemic effects of cortisone injections including cartilage damage

An ultrasound-guided genicular nerve block is typically an injection of a corticosteroid and a painkiller given around the genicular nerves to block pain signals. It is generally considered a short-term treatment.

July 2022 study: (17) “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 (18) paper describes genicular nerve ablation (radiofrequency to burn the nerves) as a percutaneous, needle-based therapy option designed to palliatively treat knee pain. As with intra-articular injection with corticosteroid, genicular nerve ablation 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. 

A July 2024 study (19) included 36 patients (average age 75.5 years old) diagnosed with knee osteoarthritis, comprising 17 bilateral cases, totaling 53 knees undergoing ultrasound guidance nerve block using a mixture of triamcinolone, ropivacaine, and lidocaine suggested ultrasound-guided genicular nerve blockade using pharmacological agents demonstrated pain reduction and improved function with a low complication rate after 12 weeks.

I cover Hyaluronic acid injections at depth in this articles:

• Research comparing different types of knee injections
• Hyaluronic acid injections general research

A May 2022 paper (20) wrote: “The utilization of hyaluronic acid for the management of knee osteoarthritis remains controversial . . ” The purpose then of this study was to evaluate changes in overall utilization and health-care costs associated with hyaluronic acid injections among Medicare beneficiaries over a contemporary time frame.”

What the researchers found was that between  2012 to 2018 total hyaluronic acid injection increased significantly this despite the 2013 American Academy of Orthopaedic Surgeons clinical practice guideline recommending against the clinical utility of these injections, hyaluronic acid injections continued to be widely implemented among Medicare beneficiaries.

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.

A December 2022 paper (21) examined the effects of autologous platelet-rich plasma combined with hyaluronic acid injection on knee inflammation in  knee osteoarthritis patients.

• 45 patients treated with only sodium hyaluronate injection after arthroscopic debridement were grouped as the control group (CG), and 54 patients treated with platelet-rich plasma combined with intra-articular injection of sodium hyaluronate after arthroscopic debridement were the observation group (OG).

The study found: Intra-articular injection of platelet-rich plasma combined with sodium hyaluronate in the treatment of knee osteoarthritis can significantly reduce the symptoms of knee joint pain, improving knee joint function and in vivo inflammatory response. The results of this study were after five weeks.

A March 2023 (22) 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.

An April 2024 study (23) compared Intraarticular botulinum toxin type A (BTA), corticosteroid and hyaluronic acid. Six studies involving 348 adults with knee osteoarthritis were included. Intra-articular Botulinum Toxin type A  showed similar effectiveness to corticosteroid. Intra-articular Botulinum Toxin type A was shown to be more effective than hyaluronic acid in improving pain, while knee stiffness and knee function were similar between groups. No serious adverse events were reported.

May 2022 study (24) 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.

A June 2022 study (25) “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 (26) 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.

A May 2024 study (27) reviewed patient data from twenty-four articles and 888 patients demonstrating that extracorporeal shockwave therapy (ESWT)  was effective for knee osteoarthritis compared with sham extracorporeal shockwave therapy (ESWT) ; however, extracorporeal shockwave therapy (ESWT)  was not effective for patients with severe knee osteoarthritis. Patients receiving higher energy or higher shock number had significant improvement than those receiving lower energy or less shock number, respectively.

A January 2022 study (28) of forty-five patients with early knee osteoarthritis were randomized into three groups.

• NSAIDs group received celecoxib 200 mg daily for 3 weeks.
• Hyaluronic acid injections group received intra-articular injection of Hyaluronic acid  once a week for 3 weeks.
• ESWT group received ESWT for 3 sessions at bi-weekly interval. All patients were followed up for one year.

All three groups showed significant improvement in pain and functional scores as well as in the collected one-year follow-up data after treatments.

• ESWT group had better pain relief than NSAIDs and Hyaluronic acid groups.
• ESWT group had better therapeutic effects in the functional scores than NSAIDs and Hyaluronic acid injections groups.

An August 2021 paper (29) 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.”

A September 2024 (30) consensus report produced by the American Society of Pain and Neuroscience (ASPN) suggested: “In well-selected individuals with certain chronic pain indications, use of injectable biologics may provide superior analgesia, functionality, and/or quality of life compared to conventional medical management or placebo.” The report included discussions on bone marrow aspirate concentrate; injectable biologics; mesenchymal stem cells and platelet-rich plasma.

It became clear to many researchers that knee 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. Again, as seen in research above, this may work well for selected patients, not all patients.

An October 2022 paper (31) 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 (32) 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.”

However, a study from McMaster University published in October 2024 (33) suggested intra-articular injection of mesenchymal stem cells (MSCs) for chronic knee pain associated with osteoarthritis probably provides little to no improvement in pain or physical function. In this study, data from 16 previously published studies and 807 patients.

In this September 2024 analysis (34), data from 11 studies were integrated to assess the efficacy of mesenchymal stem cells (MSCs) and PRP in managing osteoarthritis. the findings indicated no noticeable differences in the five different dimensions of Knee Injury and Osteoarthritis Outcome Score (KOOS) and Self-administered Western Ontario and McMaster Universities (WOMAC) index scores between the two groups. However, the International Knee Documentation Committee (IKDC Questionnaire) score was found to be higher in the PRP group compared to the mesenchymal stem cells (MSCs) group.

The researchers noted:

• KOOS is mainly employed for the assessment of therapeutic effects on knee joint injury and osteoarthropathy.
• WOMAC primarily measures the degree of knee discomfort, mobility restriction, and motor function impairment. The findings indicated that the function and condition of the knee joint were equally improved after MSCs and PRP treatment.
• IKDC mainly focuses on changes in knee function and clinical outcomes. These findings suggest that the knee function and condition following PRP treatment exhibit a modestly superior outcome compared to MSCs treatment.

• 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 (35) 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.”

A November 2024 consensus statement (36) from the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), as well as the International Cartilage Regeneration and Joint Preservation Society (ICRS) provided recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee osteoarthritis. PRP injections are considered appropriate in patients aged under 80 years with osteoarthritis knee grade 0,1,2,3 after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in grade 4 osteoarthritis.

A May 2024 study (37) examined the impact of physical therapy when combined with platelet-rich plasma. According to the researchers, exercise and treatments targeting inflammatory factors have shown the potential to alleviate knee osteoarthritis to some extent. The aim of this study was to assess the intra-articular injection of autologous platelet-rich plasma (PRP) combined with physical therapy (PT) in reducing inflammation, pain, and swelling in knee osteoarthritis.

• A total of 128 patients with knee osteoarthritis were included in the study, including 64 males and 64 females.
• The 128 patients were divided into sodium hyaluronate group (hyaluronic acid), PRP group, PRP + PT group, and PT group, with 32 cases in each group.
• Standard pain, function and disability patient reporting surveys were employed to evaluate the recovery of patients from pain and osteoarthritis.
• Compared to the (hyaluronic acid) group, the PT group, PRP group, and PRP combined with PT (PRP + PT) group all showed reduced pain and disability scores, better function, less inflammation.
• The researchers concluded: “The efficacy of intra-articular injection of PRP combined with exercise therapy in the treatment of knee osteoarthritis is superior to that of single interventions such as simple interventions of hyaluronic acid, PRP injection, and physical therapy. Furthermore, intra-articular injection of PRP combined with exercise therapy demonstrates enhanced effectiveness in improving the inflammatory levels associated with knee osteoarthritis and facilitating the rehabilitation process.”

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.

A March 2023 paper (38) compared intra-articular injection outcomes of different injection treatments including autologous conditioned serum, botulinum neurotoxin type A, corticosteroids, dextrose prolotherapy, hyaluronic acid, mesenchymal stem cells, ozone, platelet-rich plasma, plasma rich in growth factor, and stromal vascular fraction of adipose tissue. What they found was no matter the injection, when it was combined with physical therapy, the injection worked better. Some injections worked better than others. The researchers demonstrated that:

• Prolotherapy injections plus physical therapy was ranked the most effective strategy for pain reduction and global function recovery,
• Mesenchymal stem cells (MSC) plus physical therapy was the most optimal option for walking capability restoration.

More research can be found in my article Prolotherapy for knee osteoarthritis.

Alpha-2-macroglobulin (A2M), is a a naturally occurring macromolecule, a protein, that exhibits anti-inflammatory properties. A 2020 study (39) 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.

In a December 2024 study (40) , researchers found Alpha-2-macroglobulin injections were comparable in efficacy to PRP and corticosteroids in the treatment of mild-to-moderate knee osteoarthritis. However they also write: “Given its non-superior short-term efficacy compared to established intraarticular injections, as well as its increased cost of preparation, A2M may not be a justifiable option for routine treatment of knee osteoarthritis.

A January 2023 study (41) 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.”

A November 2023 paper (43) 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 2023 study (44) 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.

A November 2023 study (45) 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.”

An October 2023 paper (46)  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 (47) 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 (48) 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.

Glucosamine sulfate vs PRP for knee osteoarthritis

An August 2024 study (49) wrote: “Among the medications used to treat knee osteoarthritis, (glucosamine sulfate) and platelet-rich plasma (PRP) have become popular alternatives to painkillers or nonsteroidal anti-inflammatory drugs (NSAIDs). Although studies have shown that (glucosamine sulfate) and PRP improve clinical outcomes the researchers here presented the first direct comparison.

For the glucosamine sulfate group, patients were prescribed Viartril 500 mg 500Mg (Glucosamine Sulphate) and instructed to take three capsules once daily, totaling 1500 mg daily, before breakfast.

For the PRP group, all knee osteoarthritis patients in the PRP group were injected two times: at week 0 and at week 6.

• Three hundred eighty-two patients took Glucosamine Sulphate and 122 patients receiving PRP injections were enrolled.

Conclusions: Although the PRP group showed faster improvements in five-time sit-to-stand test (5xSST) outcomes at six weeks, from the 12-week to 1-year follow up, both the Glucosamine Sulphate and PRP groups showed significant improvements in 5xSST, time up-and-go test (TUGT), and 3-minute walk distance test (3MWDT).

A December 2023 paper (1) lists the three primary factors involved with knee preservation (the prevention of knee replacement) include joint alignment (the knee has to be straight and not bowed in or out, back or front), meniscal status (Meniscus has to be reasonably intact), and ligament stability (in particular that of the anterior cruciate ligament [ACL]). . . When a deficiency exists in one of the factors, it will affect the others.” Many doctors understand that you cannot fix one part of the knee and not address the other aspects that may cause knee instability. The authors of this study agree. They write: “For example, the ACL and posterior horn of the medial meniscus both act as restraints to anterior tibial translation (the shin bone in motion in relationship to the thigh bone). Thus, medial meniscal deficiency increases the risk for failure of ACL reconstruction, and chronic ACL insufficiency increases the risk for medial meniscus tears. Furthermore, all 3 of the factors of joint preservation have an impact on the articular cartilage status of the knee joint. Studies have shown that cartilage-preservation procedures do not result in optimal outcomes if there is joint malalignment, meniscal deficiency, or ligament deficiency.”

So here is the summary. If the medical meniscus is damaged, greater strain and likelihood of ACL tear will occur. Conversely, if the ACL is lax or weakened, that puts the medical meniscus at risk for failure or tear. Further, addressing any aspect in surgery without looking at all the problems of the knee will likely lead to unsatisfactory surgical results.

Non-surgical knee osteoarthritis treatments in Los Angeles

Call for a free phone consultation with our staff 800-300-9300

References

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