Autologous bone marrow concentrate (BMC) for the treatment of Osteoarthritis (O.A) of the Knee, Hip, and Shoulder in former n.f.l. players
Kenneth A. Pettine1, Richard K. Suzuki2, Mathew B. Murphy2, Kathryn Moncivais2, Meghana Malur2
1 BennuLife Regenerative Institute, USA
2Celling Biosciences, R&D Department, USA
The use of bone marrow concentrate, (BMC), to treat Osteoarthritis (O.A) is the standard of care in veterinary medicine. There remains a paucity of clinical data on the safety and efficacy of utilizing BMC in humans. Fifty-one former N.F.L. players were injected with BMC for shoulder (n=30), hip (n=11) or knee (n=10) osteoarthritis. All were surgical candidates. At one year follow-up up the average shoulder patient improved 68% in VAS, 64% in QuickDASH and 40% in ASES. The average hip patient improved 70% in VAS, 72% in ODI and 64% in Lower Extremity Functional Scale (LEFS). The average knee patient improved 70% in VAS, 67% in ODI and 62% in LEFS. All improvements were to a p 2. Keywords
Autologous, Regenerative Medicine, Osteoarthritis, Bone Marrow Concentrate, Mesenchymal Stem Cells, National Football League (N.F.L.)
Bone marrow concentrate (BMC), National Football League (N.F.L.), Osteoarthritis (O.A), Oswestry disability index (ODI), Visual Analog Scale (VAS), Lower Extremity Functional Scale (LEFS), QuickDASH (QD), American Shoulder and Elbow Surgeons (ASES)
Osteoarthritis (O.A) affects over 50 million Americans. This includes mostly O.A of the shoulder, hip, and knee. Shoulder osteoarthritis (O.A) has been demonstrated in cadaver and radiographic studies to affect up to 33% of patients over the age of 60 1. Patients with shoulder O.A have pain, crepitus, decreased ability to place their hand at a desired point in space and loss of motion, severely impairing activities of daily living. The nonsurgical treatments for shoulder O.A include the use of analgesics, non-steroidal anti-inflammatory medications, and shoulder exercises to maintain range of motion. The surgical treatment for shoulder O.A is total shoulder arthroplasty 1,2.
The American Academy of Orthopedic Surgeons (AAOS) recommended treatment for O.A of the hip and the knee include the following: weight loss, gentle exercise, and anti-inflammatory medications followed by total hip or knee replacement. The AAOS does not recommend arthroscopic debridement or any Hyaluronic acid products such as Synvisc®, Euflexxa™, Orthovisc®, Supartz™, or Hyalgan® for treating hip and knee osteoarthritis. Four prospective randomized studies have shown no benefit over placebo at six-month follow-up with these Hyaluronic injections. Despite the fact Hyaluronic acid products have shown no efficacy, the market for these products is several hundred million dollars per year3–8. The reason for this is the huge void between non-operative treatments and the only surgical treatment, total hip, or knee arthroplasty. Last year in the United States, over 1 million total hip and knee replacements were performed with a direct cost of over $30 billion9,10. These numbers are expected to double in the next three years (AAOS.org)9. Every day, 10,000 people in the United States turn 65 and this will continue for the next 14 years (aarp.org) increasing the population that will be in the need of total joint replacements.
Treating O.A with BMC is standard of care in veterinary medicine, primarily in dogs and horses 11–14. Research has shown that Mesenchymal Stem Cells (MSCs) obtained from BMC are superior to MSCs obtained from adipose15. There are animal studies and clinical data documenting the efficacy of injecting BMC into an arthritic joint 16–20. The primary problem in orthopedics is a lack of blood supply to the articular cartilage of the joint 1,2. Thus, the ability of the cartilage cells to repair damage is very limited. MSCs obtained from BMC have many positive attributes. MSCs are anti-inflammatory, secrete numerous growth factors, stimulate blood vessel formation, and modulate the body’s immune system to enhance healing 21. Delivering MSCs directly into the affected joint may provide therapeutic benefit.
The primary objective of this study was to determine the safety and efficacy of performing an intra-articular injection of BMC to treat shoulder, hip, and knee O.A
5. Materials and Methods
5.1 Study Design
This study is a prospective, open-label, non-randomized evaluation of autologous single BMC injection for the treatment of O.A of the shoulder, hip, or knee. All patients were counseled and consented as per IRB requirements. The treatment was offered free to study participants. The study protocol for the hip and shoulder was approved by an Institutional Review Board (IRB). Fifty-one patients were enrolled in this study. The study was performed at a single center. The details of the study design, patient demographics, bone marrow collection and processing, injection procedure and statistical tests performed are described.
All patients were former National Football League (N.F.L.) players with a primary complaint consistent with moderate to severe shoulder, hip, or knee O.A. The patients were required to have at least grade-2 changes utilizing the Kellgren-Lawrence scale for O.A22. Patients underwent a pre-injection medical history and physical examination of their shoulder (shoulder functional scale and Visual Analog Scale(VAS)) or their hip or knee (lower extremity functional scale (LEFS), Oswestry Disability Index (ODI) and VAS). In patients with bilateral O.A, only the most symptomatic shoulder, hip, or knee was injected. Follow up was obtained at three months, six months and 12 months following the procedure.
Shoulder O.A was defined by pain and stiffness in the shoulder joint, worsened by exercise and decreased shoulder range of motion. O.A in the hip or knee was defined by pain and stiffness, worsened by exercise and weight bearing. Patients being treated for shoulder O.A had radiographs of the shoulder to rate them as Kellgren -0,-1,-2,-3, or -4 on the Kellgren-Lawrence scale. There were seven patients with grade 4, 17 patients with grade 3 and 6 patients with grade 2 O.A. All patients being treated for hip and knee O.A, had standing AP and lateral radiographs as well as MRI scanning to rate them as 0, 1, 2, 3, or 4 on the Kellgren-Lawrence Scale. For the hip, there were 9 patients with Kellgren-Lawrence grade 3 changes, 1 patient with grade 2 changes, and 1 with changes in between grade 1 and 2. For the knee, there were 8 patients with Kellgren-Lawrence grade 3 changes, and 2 patients with grade 2 changes. Grade 2 changes are moderate, and grade 3 changes are moderate to severe, Grade 4 is bone on bone.
5. 2 Bone Marrow Collection and Processing
Bone marrow aspirate (BMA, 55 mL) was collected over acid citrate dextrose-anticoagulant (ACD-A, 5 ml) from the patient’s posterior iliac crest. The procedure was performed with IV sedation consisting of Versed and Fentanyl. The positioning of the Jamshidi needle in the iliac wing was confirmed by fluoroscopy. BMA was collected in a 60mL syringe in a series of discrete pulls on the plunger (targeting a collection of 5-10 mL per full), with repositioning of the needle tip between pulls based on the reported enrichment of progenitor cells by Hernigou23. The BMA was processed using the ART21 system (Celling Biosciences, Austin, TX) to produce a bone marrow concentrate (BMC) cell preparation. The 55 mL of BMA was centrifuged for 12 minutes to produce 7 mL of BMC. The 7 mL of BMC was drawn from the processing device, and glucose and bicarbonate were added to the 7 mL of BMC. The appropriate volume of BMC with the additives was immediately transferred to the physician for injection into the shoulder, hip or knee of the enrolled patient 24. Processing disposables were provided at no cost by Celling Biosciences (Austin, Texas, USA) without any further financial contributions to the study or principal investigator.
5. 3 Patient Demographics
The number of patients undergoing treatment for shoulder, hip, and knee along with average BMI and average age are shown in Table 1. All patients were candidates for total replacement of shoulder, hip, or knee.
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