Osteoarthritis Bone Marrow Lesions.

Objective: The present work aims to analyse the effectiveness of platelet-rich plasma (PRP) in degenerative knee pathology based on real-world data and to evaluate possible factors influencing the response to treatment. Methods: In total, 531 cases were analysed collecting data on gender, age, body mass index, pathology location, severity, number of cycles and route of administration. Clinical outcome was evaluated at 6 and 15 months after treatment, using the Knee injury and Osteoarthritis Outcome Score (KOOS) and obtaining percentages of Minimal Clinically Important Improvement (MCII). Blood and PRP samples were randomly tested as a quality control measure to ensure the correct properties. Comparative statistical tests and multivariate regression were performed for the analysis of the variables. Results: The PRP applied had a platelet concentration factor of 1.67, with no leukocytes or erythrocytes. The percentage of patients with MCII at 6 and 15 months after PRP application was 59.32% and 70.62%, respectively. Patients with MCII were younger ( p = 0.0246) and with lower body mass index ( p = 0.0450). The treatment had a better response in mild/moderate cases than in severe cases ( p = 0.0002). Intraosseous PRP application in severe cases improved the effect of intraarticular PRP ( p = 0.0358). The application of a second cycle of PRP only improved the response in patients without MCII at 6 months ( p = 0.0029), especially in mild/moderate cases ( p = 0.0357). Conclusion: The applications of PRP in degenerative knee pathologies is an effective treatment, but this effectiveness nonetheless depends on several variables. Real-world data can complement that from clinical trials to provide valuable information. 

https://journals.sagepub.com/doi/pdf/10.1177/1759720X221100304

Real-world evidence to assess the effectiveness of platelet-rich plasma in the treatment of knee degenerative pathology: a prospective observational study

The objective of the study was to determine the changes in clinical outcome (pain and knee activity) and assess bone/ cartilage biomarkers and inflammatory activity in persons with osteoarthritis (OA) knee following a single injection of intra-articular platelet-rich plasma (IA-PRP) and combination of intra-articular, intraosseous PRP (IA+IO-PRP).This prospective, randomized, single-blind clinical trial was conducted at a tertiary care teaching hospital in India. Ninety-six persons with OA knee with a Kellgren-Lawrence score of 3 were randomized into three groups- Group-I (IA-PRP), Group-II (IA+IO-PRP)], Group-III, [intra-articular normal saline (IA-NS)]. The primary outcome was a visual analog scale (VAS) for pain. The secondary outcomes were the Knee Injury and Osteoarthritis Outcome Score (KOOS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), bone/ cartilage turnover biomarkers [C-telopeptide (CTX-II), N-telopeptide (NTX-I), cartilage oligomeric matrix protein (COMP), N-terminal propeptide of collagen type-IIA (PIIANP), and hyaluronic acid (HA)], ultrasonography (USG) findings of the knee joint. The outcome measures were assessed at baseline, 6, and 12 weeks of follow-up.Compared to IA-NS injection, IA-PRP and IA+IO-PRP injections significantly improved VAS-pain and KOOS scores at 6 and 12 weeks. Furthermore, both PRP groups showed a significant reduction in ESR, CRP, and CTX-II at 12 weeks following PRP injections. In addition, at 12 weeks, the IA+IO-PRP group showed a significant reduction (p=0.009) in NTX-I level. Persons in the IA+IO-PRP group reported significant reductions in the synovial-effusion and infra-patellar bursitis.Significant clinical improvements were noticed following IA-PRP and IA-IO-PRP injections compared to IA-NS injections. Both PRP groups reported a significant reduction in ESR, CRP, and CTX-II levels at 12 weeks. Persons in the IA+IO-PRP group reported significant changes in u-NTX-I level and knee-USG findings. 

Comparison of clinical outcome, cartilage turnover, and inflammatory activity following either intra-articular or a combination of intra-articular with intra-osseous platelet-rich plasma injections in osteoarthritis knee: A randomized, clinical trial.

Objective: The present work aims to analyse the effectiveness of platelet-rich plasma (PRP) in degenerative knee pathology based on real-world data and to evaluate possible factors influencing the response to treatment. Methods: In total, 531 cases were analysed collecting data on gender, age, body mass index, pathology location, severity, number of cycles and route of administration. Clinical outcome was evaluated at 6 and 15 months after treatment, using the Knee injury and Osteoarthritis Outcome Score (KOOS) and obtaining percentages of Minimal Clinically Important Improvement (MCII). Blood and PRP samples were randomly tested as a quality control measure to ensure the correct properties. Comparative statistical tests and multivariate regression were performed for the analysis of the variables. Results: The PRP applied had a platelet concentration factor of 1.67, with no leukocytes or erythrocytes. The percentage of patients with MCII at 6 and 15 months after PRP application was 59.32% and 70.62%, respectively. Patients with MCII were younger (p = 0.0246) and with lower body mass index (p = 0.0450). The treatment had a better response in mild/moderate cases than in severe cases (p = 0.0002). Intraosseous PRP application in severe cases improved the effect of intraarticular PRP (p = 0.0358). The application of a second cycle of PRP only improved the response in patients without MCII at 6 months (p = 0.0029), especially in mild/moderate cases (p = 0.0357). Conclusion: The applications of PRP in degenerative knee pathologies is an effective treatment, but this effectiveness nonetheless depends on several variables. Real-world data can complement that from clinical trials to provide valuable information.

Subchondral bone marrow lesions (BMLs) are areas of disease within subchondral bone that appear as T1 hypointense and T2 hyperintense ill-defined areas of bone marrow on magnetic resonance imaging. The most common bone marrow lesions include subchondral lesions related to osteoarthritis, osteochondral defects, and avascular necrosis. Emerging therapies include autologous biologic therapeutics, in particular mesenchymal stem cells (MSCs), to maintain and improve cartilage health; MSCs have become a potential treatment option for BMLs given the unmet need for disease modification. Active areas in the preclinical research of bone marrow lesions include the paracrine function of MSCs in pathways of angiogenesis and inflammation, and the use of bioactive scaffolds to optimize the environment for implanted MSCs by facilitating chondrogenesis and higher bone volumes. A review of the clinical data demonstrates improvements in pain and functional outcomes when patients with knee osteoarthritis were treated with MSCs, suggesting that BM-MSCs can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions. Preliminary data examining MSCs in osteochondral defects suggest they can be beneficial as a subchondral injection alone, or as a surgical augmentation. In patients with hip avascular necrosis, those with earlier stage disease have improved outcomes when core decompression is augmented with MSCs, whereas patients in later stages post-collapse have equivalent outcomes with or without MSC treatment. While the evidence for the use of MSCs in conditions with associated bone marrow lesions seems promising, there remains a need for continued investigation into this treatment as a viable treatment option. 

https://doi.org/10.1016/j.bonr.2022.101630

Mesenchymal stem cells for subchondral bone marrow lesions: From bench to bedside

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.

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

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