Image Guided Injection of Anterior Cruciate Ligament Tears with Autologous Bone Marrow Concentrate and Platelets: Midterm Analysis from A Randomized Controlled Trial

Background: There has been a recent emergence in the use of orthobiologics, including platelet-rich plasma (PRP) and bone marrow concentrate (BMC), in the treatment of various musculoskeletal conditions. The goal of this study was to determine if injection of BMC and platelet products into partial and full-thickness anterior cruciate ligament (ACL) tears can facilitate primary ligament healing in patients failing conservative care, resulting in improved outcomes compared to exercise therapy.Methods: Patients were randomized to either exercise therapy or percutaneous injection of autologous BMC with PRP and platelet lysate into the ACL under fluoroscopic guidance. Pain and function were assessed at baseline and at 1, 3, 6, 12, and 24 months. Baseline and 6-month post-treatment magnetic resonance imaging (MRI) were obtained to evaluate interval healing. Laxity was assessed using the Telos device.Results: There was significant improvement in functional outcomes in the BMC group, compared to base-line for LEFS at time points 3 up to 24 months s = 0.000000005), and significant improvement in pain in the BMC group at 6 (p = 0.00054), 12 (p = 0.00127), and 24 months (p = 0.002). There was no significant improvement in pain or function at any time point in the exercise therapy group. There was significant improvement in ACL MRI ImageJ quantitative assessment in the BMC group (p = 0.001) and no difference in the exercise group (p > 0.05). No serious adverse events were reported.Conclusion: Autologous BMC and platelet product injection into ACL tears improved patient function compared to exercise, observed through 24 months. Patients treated with BMC demonstrated quantitative improvements in post-treatment MRI scans suggestive of interval ligament healing.

Evaluation of Autologous Bone Marrow Concentrate along with Hydroxyapatite-collagen for Management of Long Bone Fracture in Canines

Background: Fractures are a major concern in Veterinary orthopedic surgery because they are often complicated into non unions. The present study was planned to evaluate the fracture healing by using hydroxyapatite-collagen (HAp-Col) as a bone graft substitute and autologous bone marrow concentrate, after the internal fixation by titanium elastic pin. Method: The present work was conducted on 12 clinical cases of dogs having diaphyseal fracture of long bones. In group I (6 animals) fractures were immobilized by an internal fixation technique. In group II fracture was immobilized as in group I with use of autologous bone marrow concentrate along with Hydroxyapatite-collagen at the fracture site. The weight bearing and the progress of fracture healing were recorded. Result: Study showed early weight bearing and no observable lameness in group II as compared to group I animals. Fracture union was earlier and with minimum periosteal callus formation in one animal, five animals at 45 days and 60 days respectively while in group I fracture healing was observed in one animal, two animals at 60 day and 90 days respectively. On basis of result, it is concluded that Hydroxyapatite-collagen composite can be used as along with autolologus bone marrow concentrate as alternative therapy to bone graft in clinical cases to enhance the fracture healing. The use of autogenous and allogenic bone graft having some advantages which is overcome by this present technique.

The safety and effectiveness of bone marrow concentrate injection for knee and hip osteoarthritis: a Canadian cohort

Aim: Describe the safety and effectiveness of intra-articular bone marrow concentrate (BMC) injection to treat knee and/or hip osteoarthritis (OA) in a Canadian cohort. Materials & methods: A total of 112 patients with refractory OA received a single intra-articular injection of BMC into their knee(s) and/or hip(s). Pain, disability and quality of life were prospectively assessed prior to and 3, 6 and 12 months post-injection. Results: Outcome scores were significantly improved at all time points post-BMC injection with maximal improvement observed at 3–6 months. Improvements were unrelated to patient age, sex or radiographic OA severity. The complication rate was <2%. Interpretation: In this Canadian cohort, knee/hip OA treated with a single BMC injection resulted in significant improvements in pain, disability and quality of life and a low complication rate.

Assessing the Potential of Bone Marrow Concentrate for Cartilage Repair and Regeneration in Animal Models: A Systemic Review

Bone marrow concentrate (BMC) has been emerging as a promising regenerative source to accelerate cartilage regeneration in cartilage injuries and osteoarthritis. Though the number of stem cells in BMC is limited, BMC is rich in growth factors that promote stem cell differentiation and tissue regeneration. Despite of multiple reports available on the use of BMC for cartilage repair in humans and its use in clinical settings, only limited number of pre-clinical proof of concept studies have been reported in animal models. Hence, a systematic review focusing on the potential of BMCfor the treatment of cartilage defect in animal models has been conducted. The systematic search of literature using three popular databases, ISI Web of Knowledge, PubMed and Scopus, were conducted without year restriction. Fifteen (n = 15) studies were found appropriate and included in this review. All of the included studies were of different animal models with cartilage defect. 13 out of 15 studies reported that the usage of BMC gave the best outcome compared to other treatment methods. Most of the findings provided good scoring on the tissue repair and the histological outcome. However, most of the BMC group outcomes did not give a significant difference when compared with other interventions such as the addition of platelet rich plasma, erythropoietin, hyaluronic acid, transforming growth factor, autologous tissue implant, genetic modification or scaffoldings. In conclusion, the published studies do suggest that BMC could provide a better cartilage repair. However, more preclinical studies are required to provide definitive conclusions.

The Treatment of Bone Marrow Lesions Associated with Advanced Knee Osteoarthritis: Comparing Intraosseous and Intraarticular Injections with Bone Marrow Concentrate and Platelet Products

Background: Bone marrow lesions are a radiographic indication of bony pathology closely associated with advanced osteoarthritis of the adjacent joint. Injection of autologous orthobiologic products, including bone marrow concentrate and platelet-rich plasma, have demonstrated safety and efficacy in treating both advanced osteoarthritis (via intraarticular injection) and associated bone marrow lesions (via intraosseous injection). The relative efficacy of intraarticular versus intraosseous injection of orthobiologics has not been evaluated at the present time. Objectives: The objective was to evaluate differences in orthobiologic bone marrow lesions treatment, either as a collateral result of intraarticular injection with bone marrow concentrate and platelet products alone, or intraosseous plus intraarticular injection as measured by patient reported outcomes. Study Design: This study employed a prospective case-matched cohort design. Setting: This study took place at a single outpatient interventional orthopedic pain clinic. Methods: Using data from a prospective orthobiologic treatment registry of knee patients, a population of knee osteoarthritis with bone marrow lesions patients who had undergone only intraarticular knee injections of bone marrow concentrate and platelets (for symptomatic advanced osteoarthritis) were age, gender, and disease severity case-matched to a series of advanced osteoarthritis and bone marrow lesions patients who underwent intraosseous plus intraarticular injections. Self-reported patient outcomes for Numeric Pain Scale, International Knee Documentation Committee, lower extremity functional scale, and a modified single assessment numeric evaluation were compared between the 2 treatment groups. Results: Eighty patients were included, 40 in each group. Although pain and functional outcome scores were significantly improved in both treatment groups, there was no statistically significant differences in patient reported outcomes based on the type of treatment. Limitations: There are several limitations to this study, including multiple providers performing the injections, varying onset of symptoms to treatment, and additional injections after their initial treatment, that were not controlled. In addition, increasing the sample size may be beneficial as well, particularly with the large bone marrow lesions group, which did suggest possible improvement with intraosseous plus intraarticular over the intraarticular, although was not statistically significant in our sample. Limited data availability for this cohort as well as some missing data are other limitations to consider. Conclusion: Treating knee bone marrow lesions with intraosseous bone marrow concentrate and platelet products did not affect patient reported outcomes. Key words: Intraosseous, intraarticular, bone marrow concentrate, bone marrow lesion, bone marrow edema, knee osteoarthritis, platelet-rich plasma, injection

Use of Bone Marrow Concentrate to Treat Pain and Musculoskeletal Disorders: An Academic Delphi Investigation

Background: Acute and degenerative musculoskeletal disorders are among the most common etiologies of disability worldwide. Recently, there has been interest in the field of regenerative medicine to bridge the gap between conservative and surgical management of these conditions. Autologous bone marrow concentrate is one type of injectate that has increased in popularity over the last few decades. Though there is promising evidence supporting its efficacy, standard of care practice guidelines to govern the appropriate use and implementation of such technology are currently lacking. Objectives: The aim of this article is to report findings from a survey administered using the Delphi technique to a group of physicians using bone marrow concentrate in practice to determine best practice consensus regarding optimization of patient safety and education. Study Design: Delphi panel technique. Setting: The study was first announced at a national meeting and continued remotely across the United States via 4 rounds of online surveys. Methods: An initial panel of 30 expert members was convened and a 5-member steering committee was established. Four rounds of consensus questionnaires totaling 11 unique questions were distributed. Ten questions included a 5-point Likert scale from “Strongly Agree” to “Strongly Disagree,” and one question had a selection of 5 options regarding minimum level of evidence required. The anonymized aggregate results of each round were shared with the group prior to voting in the subsequent round in accordance with the Delphi process. Consensus was defined as 80% agreement of the statements indicating either “Strongly Agree” or “Agree” for the 10 questions with the Likert Scale and 80% agreement among 2 of 5 choices in the question regarding levels of evidence. Results: Three invited participants were excluded by the second round of questions due to lack of response in a timely manner, leaving 27 physicians queried. Nine of the 11 questions met criteria for > 80% consensus. Areas of agreement included importance of a treatment registry, candidacy grading, expanded informed consent, scientific accuracy in advertising, institutional review board approval for novel uses, performance of procedures by only licensed physicians or mid-level providers with direct physician oversight, use of image guidance for injections, data submission for publication in peer reviewed literature, and a minimum requirement of case-series level of evidence for use of bone marrow concentrate in musculoskeletal medicine. The 2 areas that did not meet criteria for consensus included online publishing of individual clinic data and standards around cell counting for dosing. Limitations: The Delphi panel of experts was convened on a voluntary basis rather than a nomination process. Our panel of experts were all physicians who use bone marrow concentrate in practice, therefore it is possible that a different panel of experts within other disciplines would reach different conclusions. Conclusions: There is significant consensus among a panel of physicians performing bone marrow concentrate injections regarding best practice guidelines for musculoskeletal conditions. Key words: Bone marrow concentrate, musculoskeletal, BMC, BMAC, injections, orthopedic, orthobiologic, Delphi method, regenerative medicine, bone marrow aspirate