Case Histories: Bone marrow stem cell therapy in patients with knee and hip osteoarthritis

Ross Hauser, MD

Stem cell therapy can be confusing to many patients because there are many services being offered as stem cell therapy. The most common are:

  • Bone Marrow derived stem cell therapy
  • Adipose (Fat cells) derived stem cell therapy

Both of these treatments are stem cells from you.

There are also stem cell therapies that are not really stem cell therapies. These are:

  • Amniotic stem cell therapy, which some are now more appropriately calling: Amniotic Membrane Injections
  • Placenta stem cell therapy, which some are now more appropriately calling: Placenta Tissue Injections

Many emails that come into our office ask us to compare the various forms of stem cell therapies. We have a very extensive series of articles discussing the different types of injections for knee pain. You can see that article here: The different types of knee injections. In addition to stem cell therapy, we talk about cortisone, Hyaluronic acid injections, Platelet Rich Plasma Therapy, Botox injections into the knee, and ozone therapy

Young stem cells versus old stem cells

Most of the emails we get are from people who have recently attended a seminar or a webinar in which they were introduced to the idea that a newborn baby was willing to donate his/her amniotic fluid or cord blood or placenta afterbirth material to them to replace the patients own old or weakened stem cells. The use of this donated material is not stem cell therapy as there has not been shown by any credible research that there are actual live stem cells in the treatment. This is discussed further in our article on “amniotic stem cell therapy.” So while these treatments may help some people, and we have seen people who responded positively to these injections, no matter what is in them, we will concentrate this article on bone marrow aspirate concentrate or as we call it bone marrow Prolotherapy. This treatment refers to the use of bone marrow concentrate injections into areas of degenerative joint disease to stop and repair degenerative changes. The use of bone marrow aspirate relies on the action of stem cells to initiate and guide this joint repair.

Mayo Clinic and Yale University studies on your own bone marrow stem cells

Doctors at the Mayo Clinic and Yale University published their research on the benefits of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis in the American Journal of Sports Medicine. (1) Here is the summary of that research:

  • Bone marrow aspirate concentrate (BMAC) is increasingly used as a regenerative therapy for musculoskeletal pathological conditions despite limited evidence-based support.
  • HYPOTHESIS: Bone marrow aspirate concentrate will prove feasible, safe, and efficacious for the treatment of pain due to mild to moderate degenerative joint disease of the knee.

In their single-blind, placebo-controlled trial, 25 patients with bilateral knee pain from bilateral knee osteoarthritis were randomized to receive Bone marrow aspirate concentrate into one knee and saline placebo into the other.

  • Early results show that Bone marrow aspirate concentrate is safe to use and is a reliable and viable (stem cell) cellular product. Study patients experienced a similar relief of pain in both Bone marrow aspirate concentrate- and saline-treated arthritic knees.

“The current literature demonstrates the potential benefits of utilizing concentrated bone marrow aspirate.”

Doctors in New Jersey at the Department of Orthopedic Surgery, Jersey City Medical Center published their findings in support of this research, in the World Journal of Orthopedics,(2) here is what the paper said:

“The current literature demonstrates the potential benefits of utilizing concentrated bone marrow aspirate for the repair of cartilaginous lesions, bony defects, and tendon injuries in the clinical setting.

The studies have demonstrated using concentrated bone marrow aspirate as an adjunctive procedure can result in cartilage healing similar to that of native hyaline tissue, faster time to bony union, and a lower rate of tendon re-rupture.”

In a 2015 study, (3) which is heavily cited by other research papers, doctors announced their findings in patients who received bone marrow stem cell therapy in the hip, knee, and ankle for treatments of osteoarthritis. All seventeen patients in the study exhibited therapeutic benefits such as increased walking distance, increased function, and reduced pain.”

Doctors publishing in the Journal of Clinical Orthopaedics and Trauma (4) cited this research among others in saying

  • “The versatility of mesenchymal stem cells (MSCs) as a treatment modality has landed it another repair target: osteoarthritis, a crippling cartilage disease that frequently afflicts the aged population. Through many studies, this newly-discovered method has been shown to significantly alleviate the pain experienced by osteoarthritic patients. “

Doctors at Georgia Regents University wrote in the Clinical and Translational Medicine (5) in support of the above research:

  • “Current pharmacological treatment strategies are ineffective to prevent the osteoarthritis progression; however, cellular therapies have the potential to regenerate the lost cartilage, combat cartilage degeneration, provide pain relief, and improve patient mobility. One of the most promising sources of cellular regenerative medicine is from mesenchymal stem cells.”

What is Bone marrow concentrate injections?

Direct Bone Marrow Injection

Using stem cells taken from a patient’s bone marrow is becoming a therapy of interest due to the potential of these mesenchymal stem cells to differentiate into other types of cells such as bone and cartilage.

Bone Marrow is the liquid spongy-type tissue found in the hallow (interior) of bones. It is primarily a fatty tissue that houses stem cells that are responsible for the formation of other cells. These mesenchymal stem cells (MSC), also called marrow stromal cells, can differentiate (change) into a variety of cell types including osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells), adipocytes (fat), fibroblasts (ligament and tendon) and others when reintroduced into the body by injection. Bone marrow also contains hematopoietic stem cells that give rise to the white and red blood cells and platelets.

Seven patient outcomes in the medical literature

In my published research in the journal Clinical Medicine Insights Arthritis and Musculoskeletal Disorders. (6) I along with my co-author Amos Orlofsky, Ph.D. of Albert Einstein College of Medicine was able to demonstrate and document these clinical results in patients receiving bone marrow-derived stem cells and dextrose Prolotherapy.

  • Seven patients with hip, knee, or ankle osteoarthritis received two to seven treatments over a period of two to twelve months of bone marrow-derived stem cells and dextrose Prolotherapy.
  • All seven patients reported improvements with respect to pain, as well as gains in functionality and quality of life.
  • Three patients, including two whose progress under other therapy, had plateaued or reversed, achieved complete or near-complete symptomatic relief, and two additional patients achieved resumption of vigorous exercise.

Patient case 1 – Ankle Pain
A 59-year-old female patient comes into our office with right ankle pain following a lateral sprain. The patient reported she could barely walk without severe ankle pain.

The patient had unsuccessful treatment with cortisone injections and was being recommended for ankle fusion based on X-ray and MRI findings that suggested osteoarthritis, avascular necrosis of the talus, and synovitis.

The patient received four bone marrow/dextrose treatments over a period of eight months.

  • At the second treatment, the patient reported the ability to stand for long periods and walk for half a mile without pain.
  • At the third treatment, she reported improved range of motion, less frequent pain, and ability to take two-mile walks on hilly, uneven ground, although steep climbs still induced pain.

Patient case  2 – Knee pain
A 69-year-old male came into our office with pain in both knees, with his right knee significantly more painful. Pain resulted in frequent sleep interruption and limitation of exercise.

The patient had received prolotherapy at another office in the previous two years but felt that the treatment has reached its maximum ability to heal.

The patient was diagnosed with osteoarthritis and received five bone marrow/dextrose treatments in each knee at two-month intervals.

  • Two months after the final treatment, the patient reported that he was completely free of pain or stiffness in both knees, had regained full range of motion, no longer suffered sleep interruption, and was no longer limited in exercise or daily life activities.

Patient case  3 – Hip Pain
A 76-year-old female came into our office with pain in both hips that had plagued her for the last 3-4 years. Her left hip pain was more significant than the right. She was unable to walk more than a mile without significant pain. The patient had received a recommendation for hip replacement. X-rays revealed moderate to severe degenerative changes in both hips.

Degenerative disease of the lower lumbar spine was also noted.

The patient received seven bone marrow/dextrose treatments to each hip over a period of 12 months and adhered to a program of daily bicycle exercise.

  • She reported incremental improvements in pain and function at each visit. At the final visit, the patient reported significant gains since the onset of treatment with respect to the range of motion, resumption of exercise, reduced crepitus, and reduction of pain medication use by two thirds. She reported her overall improvement as 90%.

Patient case  4 – Knee and hip pain
A 56-year-old female came into our office with pain in both knees and her right hip. She reported the knee pain started 3 years prior. The pain was severe in the right knee, with frequent crepitus and instability, and had forced the patient to discontinue running. MRI with a previous physician had shown cartilage degeneration. Right hip pain had been intermittent for 16 years, but instability and continuous pain began six months before her first office visit.

The hip pain prevented sleep on the affected side, bicycle exercise had stopped for more than a year, and walking exercise was limited to three miles.

MRI with a previous physician showed a hip labral tear.

The patient received bone marrow/dextrose treatments for six visits with 8–10 week intervals.

  • The patient reported modest (20%–35%) overall improvement following these treatments. At the final two visits, both knees and right hip were treated with bone marrow prolotherapy injection. During the treatment period, the left hip was also treated for pain resulting from a flexor injury incurred following visit 1.
  • Two months after visit 6, the patient reported 65%–95% overall improvement for the three joints. She is able to walk for two hours, no longer has disturbed sleep, and has been able to resume bicycle exercise with minimal discomfort.

Patient case  5 – Knee pain
A 56-year-old male came into our office with pain in both knees. The patient is a former competitive weightlifter who continues to do strength training exercises. He complained of instability in both knees during exercise, as well as sleep interruption.

The patient received 29 bilateral dextrose prolotherapy treatments over five years.

At the final prolotherapy visit, sleep interruption was still present, pain intensity was 4/10, and pain frequency was 100%.

Four months later, the patient was treated with platelet-rich plasma. Three months after plasma treatment, the patient began a series of three bone marrow stem cell injection treatments (without dextrose prolotherapy) at 2–3 month intervals.

At the time of the second bone marrow stem cell injection treatments, stability was improved. At the time of the third treatment, pain intensity was 2/10, and pain frequency was 30%. Sleep was no longer affected. These gains were maintained for nine months.

Patient case  6 – Knee pain
A 69-year-old female came into our office with pain in both knees. She had been previously diagnosed with osteoarthritis, had arthroscopic surgery to both knees eight years earlier, and medial meniscus repair in both knees 15 years earlier.

The patient reported pain occurred climbing or descending stairs and with standing or walking for two hours. Pain interrupted sleep and limited participation in racquet sports and golf.

The patient received six treatments in both knees with dextrose prolotherapy over a ten-month period.

  • After the first month of this period, the patient reported uninterrupted sleep, pain intensity of 2/10, resumption of limited golf, and an overall improvement of 50%–55%.

One year after the final prolotherapy, pain intensity had returned to 4/10 with a frequency of 20%, and sleep interruption had resumed. At this time, the patient received the first of two bone marrow stem cell injection/dextrose treatments, five months apart.

  • At the time of the second treatment, pain intensity was 1/10 with a frequency of 20%, sleep interruption was reduced by half, and patient-reported overall improvement was 90%.
  • Eight months following the final bone marrow stem cell injection/dextrose treatment, the patient reported being free of pain and able to resume full participation in all of her usual athletic activities.

Patient case  7 – Hip pain
A 63-year-old male came into our office with pain in both hips.

The patient received five treatments with dextrose prolotherapy in both hips over a period of 5 months. During this period, the patient reported an overall improvement of 50%; however, this reduced to 30%–40% at the conclusion of the treatment period, at which time pain intensity was 6/10 increased but with less frequency.

Crepitus, previously absent, was now marked. At this point, the patient began a series of two bone marrow stem cell injection/dextrose treatments two months apart.

At the time of the second treatment, pain intensity reduced. Crepitus was reduced. Specific pain manifestations previously noted, including ischial tuberosity pain and lateral hip pain, had abated, and the patient reported being able to walk without a cane for the first time in years.

Two months after the second bone marrow stem cell injection/dextrose treatments, pain intensity was 1/10 with a frequency of 10%. The patient reported walking without a limp and no longer needing a cane.

In the simplest terms, Prolotherapy is the injection of sugar water into a damaged joint. Prolotherapy injections work to heal damaged joints by stimulating nature’s healing and regenerative processes through inflammation. Prolotherapy does so by causing a controlled, specifically targeted inflammation that helps grow new ligament and tendon tissue.

Stem cell therapy in an injection of your own harvested stem cells. Stem cell therapy is typically utilized when we need to “patch” holes in cartilage and stimulate bone. We explore this option in patients when there is more advanced osteoarthritis and a recommendation for a joint replacement has been made or suggested.

Dextrose Prolotherapy provides stem cells with their favorite food. Dextrose. A little extra sugar stimulates bone marrow-derived mesenchymal stem cells to multiply in numbers.

We are going to bring in research and an important published paper from Purdue University to help understand and confirm the notion that dextrose, especially hypertonic (extra) dextrose is a significant factor in the ability of mesenchymal stem cells from bone marrow to proliferate. (7)

Simply, the researchers took stem cells and glucose and put them in an experimental situation. The experiment was to see how varying levels of glucose affected stem cell numbers (proliferation).  What the experiment found was that mesenchymal stem cell consumption of glucose increased proportionally with the glucose concentration in the medium. The more glucose, the more the stem cells ate, the more the stem cells multiplied.

In summary, hypertonic dextrose in published studies helps stem cell proliferation in vitro (in cultures.)  While this is important, more important is what it does in the human body.  We have written numerous studies on hypertonic dextrose Prolotherapy and stem cells and feel the results speak for themselves.

Do you have a question about bone marrow aspirate concentrate Prolotherapy? Get help and information from our Caring Medical staff

1 Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O’Connor MI. A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. Am J Sports Med. 2017 Jan;45(1):82-90. doi: 10.1177/0363546516662455. Epub 2016 Sep 30. [Google Scholar]
2 Gianakos AL, Sun L, Patel JN, Adams DM, Liporace FA. Clinical application of concentrated bone marrow aspirate in orthopaedics: A systematic review. World journal of orthopedics. 2017 Jun 18;8(6):491.  [Google Scholar]
Emadedin M, Ghorbani Liastani M, Fazeli R, Mohseni F, et al. Long-Term Follow-up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle, or Hip Osteoarthritis. Arch Iran Med. 2015 Jun;18(6):336-44. doi: 015186/AIM.003.  [Google Scholar]
4 Afizah H, Hui JH. Mesenchymal stem cell therapy for osteoarthritis. Journal of clinical orthopaedics and trauma. 2016 Sep 30;7(3):177-82.  [Google Scholar]
5 Burke J, Hunter M, Kolhe R, Isales C, Hamrick M, Fulzele S. Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis. Clinical and translational medicine. 2016 Aug 10;5(1):27.  [Google Scholar]
6 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. [Google Scholar]
7 Deorosan B, Nauman EA. The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells. Stem Cell International. 2011;  Article ID 429187, 12 pages. Doi:10.4061/2011/429187 [Google Scholar]

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