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Scientific literature review: BMC (Bone Marrow Concentrate) for the treatment of osteoarthritis

Bone marrow concentrate (BMC) has been used for the treatment of osteoarthritis for several years now. Whilst the scientific literature demonstrates the benefits of the treatment, unfortunately some of the publications available have some shortcomings. This includes the use of a small number of patients and the lack of a randomised control group. There are however a few exceptions to this rule and there have more recently been some high-quality publications demonstrating the long-term benefits of using BMC in patients with osteoarthritis of the knee as well as avascular necrosis of the knee and the hip (see below). At the Orthobiologics Clinic we are excited by the potential benefits BMC can offer for patients with pain caused by osteoarthritis and avascular necrosis. BMC contains a potent mix of stem cells, stem cell precursors, growth factors, bone proteins and anti-inflammatory substances. We feel that this is a valuable treatment with promising outcomes. We’re looking forward to seeing more prospective randomised trials comparing BMC with other treatments such as steroid injections.

Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: a prospective randomized study versus contralateral arthroplasty at a mean fifteen-year follow-up

Philippe Hernigou , Jérôme Delambre , Steffen Quiennec , Alexandre Poignard (2020)

This study compares two ways of treating patients with osteoarthritis of the knee. Traditionally patients will undergo knee replacement surgery once all other treatment options have been explored. The authors report on a cohort of 140 patients who were supposed to undergo bilateral knee replacement surgery but underwent an injection with stem cells from bone marrow concentrate (BMC) on one side while having the other knee replaced during the same anaesthetic. The bone marrow concentrate was injected not into the knee joint, but into the bone next to the knee joint, specifically into areas that are called bone marrow lesions. These lesions can be seen on MRI scans and are felt to contribute to the progression of osteoarthritis. Patients were followed up for an average of 15 years. Only 18 out of 140 knees treated with BMC eventually required total knee replacement (TKR) surgery after an average of 10 years following the initial stem cell injection. 21 knees from the initial TKR group required further revision surgery during the same observation period. The authors also observed that patients with large bone marrow lesions after BMC treatment were more likely to require knee replacement surgery in the future. The authors concluded that injection treatment of bone marrow lesions with BMC stem cells had sufficient effect to postpone or avoid the need for knee replacement surgery in this group of patients with bilateral knee osteoarthritis.

At the Orthobiologics Clinic we were impressed with this publication by Philippe Hernigou and colleagues. This was a well-designed trial with a sufficiently large number of patients and long follow up. It is quite clear that injecting bone marrow lesions with BMC stem cells in patients with osteoarthritis of the knee can help avoid the need for subsequent knee replacement surgery. We feel that this is an exciting field of research that gives patients a new and valuable alternative treatment option to traditional joint replacement surgery.

Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study

Philippe Hernigou , Charlie Bouthors , Claire Bastard , Charles Henri Flouzat Lachaniette , Helene Rouard , Arnaud Dubory (2020)

Traditional injection treatments for osteoarthritis always deliver the therapeutic substance of choice directly into the cavity of the affected joint. This group of authors investigated whether injecting bone marrow stem cells into the subchondral bone right next to arthritic joints is a viable treatment option. The authors recruited 120 patients with equally bad osteoarthritis of both knees. All patients were treated with bone marrow concentrated stem cells (BMC). During the same anaesthesia one knee received an injection with BMC into the cavity of the joint, while in the other knee the BMC was injected into the subchondral bone (that is the bone directly next to the arthritic joint). Patients were followed up for 15 years. In the subchondral bone injection group, the risk of requiring joint replacement surgery was 1.3% per knee-year, while the risk was 4.6% per knee-year in the joint injection group. After 15 years 20% of the patients in the subchondral bone injection group had undergone joint replacement surgery, while 70% of the patients in the joint injection group ended up with a new knee joint. Among those patients who did not require any joint replacement surgery on either side, all preferred the knee with the subchondral bone injection with BMC stem cells.

At the Orthobiologics Clinic we were excited to see yet another well-designed publication by the group of Hernigou and colleagues, this time investigating the ideal site of injection of bone marrow-derived stem cells. Injecting the subchondral bone might seem counter-intuitive, but the results speak for themselves: Injecting bone marrow concentrate (BMC) into the subchondral bone of patients with osteoarthritis of the knee works better than injecting BMC into the cavity of the knee joint. Hernigou and colleagues have done a lot of ground-breaking work in the field of stem cell treatment and we feel they need to be congratulated for their valuable contribution!

Cell therapy versus simultaneous contralateral decompression in symptomatic corticosteroid osteonecrosis: a thirty-year follow-up prospective randomized study of one hundred and twenty five adult patients

Philippe Hernigou, Arnaud Dubory, Yasuhiro Homma, Isaac Guissou, Charles Henri Flouzat Lachaniette, Nathalie Chevallier, Hélène Rouard (2018)

Avascular necrosis of the hip is a rare, but well-known condition where the blood supply to the head of the femur gets interrupted. As a result, the head can crumble and collapse. Patients often end up with a total hip replacement, sometimes at a comparably young age. Core decompression can sometimes halt the decline, but the results have traditionally been rather mixed. In this study the authors investigated a series of 125 patients with bilateral early-stage avascular necrosis (AVN) of the hip. One hip was treated with core decompression, the other underwent core decompression and injection with stem cells taken from the iliac crest (BMAC/BMC). After an average follow-up of 25 years the rate of collapse of the femoral head was 72% in the core decompression group and 28% in the stem cell group. 76% of patients in the core decompression group had undergone total hip replacement, but the rate was only 24% in the stem cell group.

At the Orthobiologics Clinic we were impressed with what we felt was a true landmark paper: A difficult to treat condition, a large cohort of patients with bilateral AVN, randomisation with a control group and a very long follow-up. The benefits of the added BMAC stem cells are obvious: those hips treated with added stem cells were 3 times less likely to require total hip replacement surgery in the future!

Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee

Philippe Hernigou, Jean Charles Auregan, Arnaud Dubory, Charles Henri Flouzat-Lachaniette,Nathalie Chevallier, Helene Rouard (2018)

This publication reports on the outcomes of patients with a diagnosis of osteonecrosis (avascular necrosis) of the knee as a result of corticosteroid treatment. This is a problem that is traditionally treated with Total Knee Arthroplasty (TKA) once all other treatments have been exhausted. However, TKA in these patients often result in poor outcomes with a high rate of revision surgery. The authors recruited 30 patients with bilateral osteoarthritis of the knee secondary to corticosteroid induced avascular necrosis. All patients underwent simultaneous TKA on one side while undergoing injection of bone marrow concentrate (BMC) into the subchondral bone (the are of bone next to the joint surface) of the other knee joint. After an average follow-up of 12 years only one patient in the BMC group required further surgery while 6 knee replacements had to undergo further procedures. 21 patients preferred the knee treated with BMC while 9 patients preferred the knee with TKA.

This is another landmark paper from the same group of authors who published the above-mentioned trial on BMC in the treatment of avascular necrosis of the hip with excellent results in patients treated with BMC. We were impressed with the excellent results reported in this cohort of patients who underwent subchondral BMC injection vs TKA. Bilateral avascular necrosis of the knee secondary to corticosteroid induced avascular necrosis of the knee is a rare condition. Recruiting 30 patients into a prospective randomised trial and reporting on the outcome after 8-16 years is a major achievement. Even more impressive are the results! Not only was the surgical time for BMC much quicker than for knee replacement, but there were also fewer complications and re-operations in the BMC group. We noted that the scientific knee scores were similar in both groups, but 2/3rd of patients preferred the knee that was treated with BMC over the knee that underwent knee replacement. At the Orthobiologics Clinic we were impressed with the excellent results achieved with the use of bone marrow concentrate in the treatment of this rare condition of the knee!

Clinical outcome of autologous bone marrow aspirates concentrate (BMAC) injection in degenerative arthritis of the knee

Jae-Do Kim, Gun Woo Lee, Gu Hee Jung, Cheung Kue Kim, Taehun Kim, Jin Hyung Park, Seong Sook Cha, Young-Bin You (2013)

The investigators treated 45 patients (75 knees) with osteoarthritis of the knee with a single bone marrow and adipose fat concentrate injection. Patients were then followed up at 3,6 and 12 months. The authors concluded that BMC injections significantly improved both knee pain and function in patients with degenerative arthritis of the knee. In addition to this, the injection has been shown to be more effective in the early to moderate stages of arthritis, and even patients with severe arthritis showed improvements following BMC treatment.

At the Orthobiologics Clinic we feel it is unusual to combine bone marrow derived stem cells with those derived from abdominal fat. However unusual the combination, the treatment appears to work well for patients with mild and moderate osteoarthritis. Patients with severe osteoarthritis still saw improvements, but not to the same extent. We would be interested to see whether the treatment benefits can be seen for more than 1 year. We would also be interested to see how this combination treatment compares to treatment with a placebo.

Clinical Outcome of Bone Marrow Concentrate in Knee Osteoarthritis

Kristin S. Oliver, MD, Matthew Bayes, MD, David Crane, MD, Chakrapani Pathikonda (2015)

The authors analysed the data of 70 patients who underwent treatment with bone marrow concentrate (BMC) and lipo-aspirate for osteoarthritis of the knee. Patients were followed up for 180 days. The average scores for pain, activity, quality of life and sporting activities improved significantly. The authors concluded that this study of intra-articular injection of autologous bone marrow concentrate and lipo-aspirate in patients diagnosed with knee osteoarthritis demonstrates encouraging results for positive outcomes without complications. Further study with randomized controlled trials is warranted to prove the potential of this intervention.

At the Orthobiologics Clinic we were pleased to see a trial involving a larger number of patients demonstrating good outcomes. However, the short follow up of only 180 days and the lack of a placebo control group makes it difficult to ascertain the true long-term benefits of the treatment.

A prospective multi-site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis

Christopher J Centeno, Hasan Al-Sayegh, Jamil Bashir, Shaun Goodyear, Michael D Freeman (2015)

The authors treated 102 patients (115 shoulders) who were diagnosed with osteoarthritis of the shoulder and/or rotator cuff tears with bone marrow concentrate (BMC) and PRP (platelet rich plasma). Patients reported a continued improvement in outcome scores for up to 2 years. The self-rated improvement was 48.8%. The results were the same for patients with arthritis and/or rotator cuff tears. The authors concluded: The use of BMC to treat symptomatic rotator cuff tears and glenohumeral OA is promising, and in an uncontrolled treat¬ment registry population, effective at both reducing pain and improving function. Randomized clinical trials are required to confirm the efficacy of BMC injections for treatment of shoulder OA and rotator cuff tears.

At the Orthobiologics Clinic we have noticed some flaws in the methodology of the publication such as the mixing of patients with arthritis and rotator cuff tears and the failure to report the average follow-up times. Within those limitations however, it looks as if the treatment protocol led to an obvious improvement in pain and function.

Bone Marrow Concentrate Therapy Improves Short-Term Outcomes In Patients With Symptomatic Hip Osteoarthritis

K.E. Whitney, K.K. Briggs, I.K. Bolia, M.J. Philippon, T.A. Evans (2018)

The investigators followed up 17 patients (19 hips) for 3 to 6 months. All patients received an injection with bone marrow concentrate for symptomatic osteoarthritis of the hip. Outcome scores for pain and function improved significantly. The authors concluded: These results suggest that BMC therapy for the treatment of hip OA can improve hip function and reduce pain over 6 months.

At the Orthobiologics Clinic we were a bit disappointed with the short follow up and the small number of patients in this study. Nevertheless, this is one of the few publications looking into the treatment of hip arthritis with bone marrow concentrate (BMC) and the reported outcomes are promising.

Functional Outcomes Following Microfragmented Adipose Tissue Versus Bone Marrow Aspirate Concentrate Injections for Symptomatic Knee Osteoarthritis

Kenneth Mautner, Robert Bowers, Kirk Easley, Zachary Fausel, Ryan Robinson (2019)

To our knowledge this is the first publication directly comparing the outcomes between treatment with mesenchymal stem cells obtained from either bone marrow or adipose fat. The authors used the Lipogems system to obtain the adipose fat graft. 76 patients (106 knees) with osteoarthritis of the knee were included. Patients in the bone marrow group were followed up for 1.8 years while patients in the adipose fat (Lipogems) group were followed up for 1.08 years. At the time of the final follow-up there was a significant improvement in pain and function scores in both groups. There was no significant difference in outcomes between the groups. The authors concluded that this is a novel study that compares outcomes between bone marrow and adipose tissue derived orthobiologic injections for symptomatic knee arthritis. Based on our data, the autologous tissue source does not affect outcomes as both BMC and MFAT (Lipogems) groups had significantly improved pain and function compared with their baseline without a significant difference in improvements between the two treatment groups.

At the Orthobiologics clinic we were delighted to see that both treatments work equally well, although we would welcome a randomised controlled trial investigating this issue further.

A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up.

Centeno C, Sheinkop M, Dodson E, Stemper I, Williams C, Hyzy M, Ichim T, Freeman M (2018)

In this trial 48 patients with osteoarthritis of the knee were randomly allocated to either treatment with exercise therapy or injection with bone marrow concentrate. After 3 months of exercise therapy patients were given the option of crossing over into the bone marrow group and all these patients chose to do so. After 2 years patients showed a significant increase in outcome scores regardless of whether they underwent exercise therapy at the beginning or not.

At the Orthobiologics Clinic we were excited by the headline promising a comparison between exercise therapy and bone marrow concentrate. However, on closer inspection all patients in the physiotherapy group crossed over into the bone marrow group already after 3 months. These methodological shortcomings make a true comparison impossible. At the same time, we were pleased to see the good outcome scores following treatment with bone marrow concentrate after 2 years!

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