Caring Medical - Where the world comes for ProlotherapyAvoiding knee replacement | Stem cell therapy and advanced knee osteoarthritis

Ross Hauser, MD and  Katherine L. Worsnick, MPAS, PA-C 

In this article, we will examine the medical research concerning the effectiveness of stem cell therapy and bone repair in knee osteoarthritis. Stem cell therapy is part of our comprehensive Prolotherapy treatment program on stimulating joint repair in patients with knee osteoarthritis.

Before we begin this article, a brief explanation of stem cell therapy. In our offices, we rely mainly on a comprehensive program of Prolotherapy injections. These injections are simple dextrose solutions. In our more than 25 years experience we have found, published and reported on the medical literature surrounding the effective use of these simple, much less costly treatments. We have a very extensive article on our website in support: The evidence for Prolotherapy Injections when the recommendation is Knee Replacement.

When we do rely on stem cell therapy, it is usually in the form of bone marrow aspirate or bone marrow-derived stem cell therapy. We have found, published and reported on the medical literature surrounding the effective use of bone marrow stem cells. You can find this research here: Bone marrow stem cell therapy and Prolotherapy | Published review 7 case histories.

If you are reading this article it is possible that you have researched stem cell therapy and you have come upon products from donated afterbirth material such as amniotic fluid, placenta tissue, cord blood etc. As mentioned, our clinic has been offering regenerative medicine for over 25 years. We have always explored many new healing opportunities for our patients. While amniotic material therapy may provide results for some, we do not offer it because the results are not consistent, the cost is more prohibitive, and many of the claims made are not backed by good science. Please refer to this article for more information: Amniotic Stem Cell Therapy.

The treatment of more advanced knee osteoarthritis and bone/joint erosion with stem cell therapy and Prolotherapy

In the weight-bearing knee joint, bone constantly adapts to the load demands placed on the joint. For instance, if you were to gain a lot of weight, the bone adapts to support that weight. If you perform a repetitive and physically challenging motion with high demand on your joints, the bone remodels itself to provide stability. If you suffer from joint instability from the soft-tissue breakdown, the bone adapts sometimes in the form of bone spurs.

How does the bone adapt? By remodeling. The bone is redefining itself by breaking itself down and reconstructing itself to provide the joint, be it the ankle, knee, hip, spine, shoulder etc, the stability to function as best it can.

How your knee instability accelerates the need for knee replacement by making you produce a far inferior bone

No one wants to produce inferior bone. Professor Tuhina Neog of Boston University School of Medicine, published her research in the journal Therapeutic advances in musculoskeletal disease in which she describes the “Clinical significance of bone changes in osteoarthritis.” Here are some of the points made:

  • There is mounting evidence that degenerative wear and tear of the subchondral bone (bone under the cartilage) plays a much more important role in osteoarthritis than thought.
  • Surgical specimens from persons with osteoarthritis have demonstrated that subchondral bone changes, including subchondral bone attrition which is a flattening or depression of the subchondral bony surface, are common. (Which also makes knee replacement tricky if the bone is subpar).

Further, in its desire to quickly repair and remodel itself to meet the challenges of degenerative joint disease, the bone increases its turnover rate and produces a far inferior bone with less mineralized than normal bone.

With alterations in its properties, the subchondral bone may be less able to absorb and dissipate energy, thereby increasing forces transmitted through the joint and predisposing the articular surface to deformation. It has been proposed that these changes in the subchondral bone could adversely affect the biomechanical environment of the overlying cartilage, predisposing the cartilage to subsequent loss of integrity.(2)

What does all this mean? In some cases, it is loss of bone by way of degenerative erosion that causes cartilage destruction and not vice-versa. Your bones made you “bone on bone.”

In examining this and other research it is easy to see why doctors around the world have focused their attention on the challenges of repairing and regenerating osteochondral defects (the bone on bone phenomena and accompanying bone destruction in osteoarthritic joints) by controlling the body’s inflammatory response to healing. This is a remarkable transformation away from joint replacement.

How to use healing inflammation such as in stem cell therapy or Prolotherapy to repair bone on bone is a difficult problem for many doctors to understand. They cannot grasp the concept of inflammation as healing medicine.

Unfortunately for some patients, the promise of regenerative medicine, the non-surgical restoration and transformation of diseased joints into pain-free and functional joints, is not met because the one thing all the promising research  suggests but never spells out clearly is that for this medical transformation to occur you need doctors to transform themselves from expert surgeons into doctors expert in managing healing inflammation.

Inflammation is a difficult problem for many doctors who practice in the world of anti-inflammatory medications to understand. They understand the research that says non-steroidal anti-inflammatory medications can be very harmful to healing, they also understand the significant problems, even joint destruction caused by corticosteroids injections. But they cannot grasp the concept of inflammation as healing medicine.

Countdown to knee replacement: Doctors damage the inflammatory healing process when inflammation is needed the most.

The difficulty in doctors determining the difference between regenerative treatments (which require inflammation to heal) and non-regenerative conservative care (anti-inflammatory medicine) was highlighted in research from doctors in Germany who were exploring alternatives to knee replacement surgery. Writing in the medical journal Therapeutic Advances in Musculoskeletal Disease they note that doctors are often confused by the term “conservative care.” Conservative knee care of course means, non-surgical treatments and anti-inflammatory medications.

Amazingly, treatments such as Platelet Rich Plasma, Stem Cell Therapy, and Prolotherapy are thought of, if thought of at all, after the use of anti-inflammatories and painkillers derail and impede the natural healing process of the body. We damage the inflammatory healing process when inflammation is needed the most.

Our treatment: Injecting healing inflammation to repair osteoarthritic bone in the knee

In this section, we will examine the role of inflammation and bone repair.

This is research published in the Journal of Orthopaedic Trauma lead by the  Academic Department of Trauma & Orthopaedic Surgery, University of Leeds, Leeds, United Kingdom. The research examines the role of anti-inflammatory medications and acute broken bone damage. Here are the research take-home points:

  • In fracture healing – the state of inflammation dominates the initial phase of healing, but the ideal magnitude and duration of the process for an optimal outcome remains obscure.
    • What is being said here? The bone needs inflammation to heal – knowing what the right amount of inflammation is, is difficult for doctors to understand.
  • Non-steroidal anti-inflammatory drugs frequently administered for pain management after trauma fracture (and in surgery) continue to be a cause of concern for a successful bone repair response because they stop the inflammatory healing process.(3)

Anti-inflammatories compromise the broken bone’s ability to heal properly. What are they doing then to your osteoarthritic knee?

For more research on stem cells and the ability to repair bone damage, please see my article Stem cell therapy and bone repair in osteoarthritis patients

To heal a diseased knee joint you need to treat the whole knee joint. You cannot rely solely on repairing the cartilage or the meniscus or the bone. You must also repair the knee instability that caused the knee degeneration in the first place.

In March 2017, researchers in Italy published new research address the understanding that you must treat the whole knee. Here is what they said:

  • Although articular cartilage is the target of osteoarthritis, its deterioration is not always clearly associated with patient symptoms. (In other words, you can have bone on bone, no cartilage, with no knee pain). Because a functional interaction between cartilage and bone is crucial, the pathophysiology of osteoarthritis and its treatment strategy must focus also on subchondral bone.
    • The Italian researchers then investigated whether adipose-derived stromal cells (ASCs – fat stem cells) injected into a joint at two different concentrations could prevent subchondral bone damage after the onset of mild osteoarthritis in rabbit knees.
    • Conclusion: “We found that (adipose stem cells) promoted cartilage repair and helped counteract the accelerated bone turnover (degeneration) that occurs with osteoarthritis.(4)

In other words, you must not only understand the cartilage, but you must also understand the bone, and you must understand the ligaments. If you do not recognize all these components, stem cell therapy may not achieve the desired healing results.

Stem Cell Prolotherapy

Stem cell signal the healing of bone repair

One of the most studied factors in stem cell repair is perhaps one of the most intriguing – the “paracrine effect.” This is where stem cells introduced into a damaged area assess the damage and then sends out chemical signals to nearby cells to start repairing the damage. The results below are fascinating.

  • In one study doctors from Columbia’s National University looked at the ability of stem cells derived from human adipose (fat) tissue to repair surgical bone lesions in animal models. The results demonstrated that stem cells induced bone regeneration mainly by releasing paracrine factors (chemical messages) that “jump started’ the repair process.(5)
  • This was supported by later research from Japan in a paper titled “The paracrine effect of adipose-derived stem cells inhibits osteoarthritis progression.”(6)

Stem cells repair bone at the level of the micro world

In a very recent study, doctors in China focused on the crucial function of stem cells in bone regeneration by looking at the “osteogenic microenvironment,”  the micro world of the non-repaired joint. They examined why joints don’t heal and how they could be repaired with stem cells.

They centered on the role of inflammation in changing the microenvironment from non-healing to healing. In a damaged joint, the body reacts through two main mechanisms – remove damaged tissue, repair damaged tissue. If the body removes more than it can repair you have degenerative joint disease.

What they found was controlled inflammation brought the healing cells into the joint and the “raw material” to start rebuilding – simultaneously. As the building materials arrived the healing cells arrived. A balance was reached as repair exceeded removal the joint was revitalized.

Their conclusion in the scientific language with our explanations added:

“The results indicated that conditioned medium from inflammatory cytokine-activated MSCs (stem cells “inspired to heal” by pro-inflammatory protein signals) can:

  • significantly promote osteoblast proliferation (bone remodeling and repair),
  • migration (getting to the site of the damage),
  • differentiation (multiply their numbers once at the site of the wound),
  • and mineralization and ultimately enhance osteogenesis (bone repair) through paracrine mechanisms (the stem cells created a blue print for repair and provided directions to repair cells on how to get to the site of the damage).
  • These findings present a new direction for the clinical application of stem cells.”(7)

Bone disintegration and RANKL inhibitors

As we mentioned above, joint repair is through two mechanisms:

  • (1) removing bone damage to  make way for
  • (2) new bone remodeling. In new research doctors have found that not only do stem cells jump-start the repair process, they also negotiate with the breakdown process to prevent overzealous destruction by RANKL (scientifically Receptor activator of nuclear factor kappa-B ligand).

For those of you who have been prescribed RANKL inhibitors, it may have been explained to you that your body is producing too much of this protein from the Tumor Necrosis Family, (a family of cells that cause cell death.) What RANKL does is secrete acids to disintegrate bone. This is a beneficial function when controlled, as explained above, it is simply out with the old bone, in with the new, the skeletal system grows and gets stronger through this function. It is not beneficial when too much material is removed, thus the prescriptions for RANKL inhibitors.

Doctors in Japan examined patients with medication-induced jaw bone loss. When they intravenously introduced stem cells, they found that not only did the stem cells send repair signals, they also sent signals to the osteoclasts (bone cells that absorb damaged bone) to regulate the amount of bone they were absorbing. In other words, the stem cells stopped the degenerative process so they could fix the damaged bone – they inspired a new bone recycling process using the damaged bone.(8)

When doctors recommend to patients that they need joint replacement surgery, they base this mainly on the diagnosis of bone disintegration in the joint – the diseased bone must be amputated and replaced.

The need to find an effective way to fix bone defects in osteoarthritis is one of the most serious problems facing doctors today. This is why researchers have focused their attention on tissue regeneration therapies including mesenchymal stem cell therapyStem Cells have been used for the treatment of osteogenesis imperfect (extremely fragile bones), osteonecrosis (bone death) of the femoral head, osteoporosis, rheumatoid arthritis and osteoarthritis with good success.(9)

Caring Medical and Rehabilitation Research: Stem Cell Prolotherapy for knee pain

In a study published in the journal Clinical medicine insights. Arthritis and musculoskeletal disorders by our Caring Medical research team, our doctors examined the use of a simple, cost-effective regenerative treatment using direct injection of bone marrow stem cells into osteoarthritic joints in combination with dextrose Prolotherapy. Seven patients with hip, knee or ankle osteoarthritis received two to seven treatments over a period of two to twelve months. All patients reported improvements with respect to pain, as well as gains in functionality and quality of life. Three patients, including two whose progress with another therapy had plateaued or reversed, achieved complete or near-complete symptomatic relief, and two additional patients achieved resumption of vigorous exercise.

“We have explored whole bone marrow injection in combination with dextrose prolotherapy as a cost-effective approach with the potentially broad application for osteoarthritis in non-specialized settings. Our initial experience has been encouraging, as all patients experienced significant gains in treatment periods of 2–12 months without adverse events.”(10)

Do you have a question about your knee pain? You can get help and information from our Caring Medical Staff

Prolotherapy Specialists

1 Neogi T. Clinical significance of bone changes in osteoarthritis. Arthritis research & therapy. 2012 Mar 8;14(2):A3. [Google Scholar]
2 Wehling P, Moser C, Maixner W. How does surgery compare with advanced intra-articular therapies in knee osteoarthritis: current thoughts. Therapeutic advances in musculoskeletal disease. 2016 Jun;8(3):72-85. [Google Scholar]
3 Giannoudis PV, Hak D, Sanders D, Donohoe E, Tosounidis T, Bahney C. Inflammation, bone healing, and anti-inflammatory drugs: an update. Journal of orthopaedic trauma. 2015 Dec 1;29:S6-9. [Google Scholar]
4 Parrilli A, Giavaresi G, Ferrari A, Salamanna F, Desando G, Grigolo B, Martini L, Fini M. Subchondral bone response to injected adipose-derived stromal cells for treating osteoarthritis using an experimental rabbit model. Biotech Histochem. 2017 Mar 20:1-11. [Google Scholar]
5. Linero I, Chaparro O. Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One. 2014 Sep 8;9(9):e107001. doi: 10.1371/journal.pone.0107001. eCollection 2014. [Google Scholar]
6. Kuroda K, Kabata T, Hayashi K, Maeda T, Kajino Y, Iwai S, Fujita K, Hasegawa K, Inoue D, Sugimoto N, Tsuchiya H. The paracrine effect of adipose-derived stem cells inhibits osteoarthritis progression. BMC musculoskeletal disorders. 2015 Sep 3;16(1):236. [Google Scholar]
7. Li C, Li G, Liu M, Zhou T, Zhou H. Paracrine effect of inflammatory cytokine-activated bone marrow mesenchymal stem cells and its role in osteoblast function. J Biosci Bioeng. 2015 Aug 24. [Google Scholar]
8. Ogata K, Katagiri W, Hibi H. Secretomes from mesenchymal stem cells participate in the regulation of osteoclastogenesis in vitro. Clin Oral Investig. 2016 Oct 29. [Google Scholar]
9. Wimpenny I, Markides H, El Haj AJ. Orthopaedic applications of nanoparticle-based stem cell therapies. Stem Cell Research & Therapy 2012, 3:13. [Google Scholar]
10 Hauser RA, Orlofsky A. Regenerative injection therapy with whole bone marrow aspirate for degenerative joint disease: a case series. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2013 Jan;6:CMAMD-S10951.



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