<b>PURPOSE: </b>This study was performed to compare the efficacy of treatment in three groups of patients with knee osteoarthritis (OA) given an intra-articular injection of platelet-rich plasma (PRP), hyaluronic acid (HA) or ozone gas.<b>METHODS: </b>A total of 102 patients with mild-moderate and moderate knee OA who presented at the polyclinic with at least a 1-year history of knee pain and VAS score ≥4 were randomly separated into three groups. Group 1 (PRP group) received intra-articular injection of PRP × 2 doses, Group 2 (HA group) received a single dose of HA, and Group 3 (Ozone group) received ozone × four doses. Weight-bearing anteroposterior-lateral and Merchant's radiographs of both knees were evaluated. WOMAC and VAS scores were applied to all patients on first presentation and at 1, 3, 6 and 12 months.<b>RESULTS: </b>At the end of the 1st month after injection, significant improvements were seen in all groups. In the 3rd month, the improvements in WOMAC and VAS scores were similar in Groups 1 and 2, while those in Group 3 were lower (p < 0.001). At the 6th month, while the clinical efficacies of PRP and HA were similar and continued, the clinical effect of ozone had disappeared (p < 0.001). At the end of the 12th month, PRP was determined to be both statistically and clinically superior to HA (p < 0.001).<b>CONCLUSION: </b>In the treatment of mild-moderate knee OA, PRP was more successful than HA and ozone injections, as the application alone was sufficient to provide at least 12 months of pain-free daily living activities.<b>LEVEL OF EVIDENCE: </b>Therapeutic study, Level I.
<b>PURPOSE: </b>To compare the effectiveness of intraarticular (IA) multiple and single platelet-rich plasma (PRP) injections as well as hyaluronic acid (HA) injections in different stages of osteoarthritis (OA) of the knee.<b>METHODS: </b>A total of 162 patients with different stages of knee OA were randomly divided into four groups receiving 3 IA doses of PRP, one dose of PRP, one dose of HA or a saline injection (control). Then, each group was subdivided into two groups: early OA (Kellgren-Lawrence grade 0 with cartilage degeneration or grade I-III) and advanced OA (Kellgren-Lawrence grade IV). The patients were evaluated before the injection and at the 6-month follow-ups using the EuroQol visual analogue scale (EQ-VAS) and International Knee Documentation Committee (IKDC) subjective scores. Adverse events and patient satisfaction were recorded.<b>RESULTS: </b>There was a statistically significant improvement in the IKDC and EQ-VAS scores in all the treatment groups compared with the control group. The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups. There was no significant difference in the scores of patients injected with one dose of PRP or HA. In the early OA subgroups, significantly better clinical results were achieved in the patients treated with three PRP injections, but there was no significant difference in the clinical results of patients with advanced OA among the treatment groups.<b>CONCLUSION: </b>The clinical results of this study suggest IA PRP and HA treatment for all stages of knee OA. For patients with early OA, multiple (3) PRP injections are useful in achieving better clinical results. For patients with advanced OA, multiple injections do not significantly improve the results of patients in any group.<b>LEVEL OF EVIDENCE: </b>I.
UNLABELLED: : Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 10(6) cells), medium dose (10 × 10(6)), and high dose (50 × 10(6)). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy.
SIGNIFICANCE: Although this phase I study included a limited number of patients without a placebo arm, it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis. This study also provides encouraging preliminary evidence of efficacy. Larger and controlled long-term studies are now mandatory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis.
The use of biologic adjuvants in the treatment of operative and nonoperative orthopedic injuries continues to expand in concert with our understanding of the acute and chronic healing process of musculoskeletal injuries. Stem cell treatments in orthopedics are among the most commonly explored options, and have found varying levels of success in promoting osseous and soft tissue healing. Basic science and translational studies have demonstrated the potential for broad application of stem cells in the treatment of a growing number of musculoskeletal injuries. Emerging clinical studies have also provided promising results, although the vast majority of studies have featured small sample sizes and limited duration of follow-up. In addition, a number of important questions remain regarding the clinical safety, treatment delivery, and overall efficacy of stem cell augmentation of injured tissue in orthopedics. The objective of the current review is to present a broad overview of the current state of stem cell treatments in orthopedic surgery, with an emphasis on soft tissue healing. This review of stem cell treatment covers the basic science behind biologic augmentation, advantages of the various stem cell sources, preclinical results, and current and future clinical applications.
The use of platelet-rich plasma (PRP) injections in the treatment of musculoskeletal conditions has become more prevalent in recent years. Current literature has exhibited that PRP injections are relatively safe and can potentially accelerate or augment the soft tissue healing process. This review presents the most current literature update on the use of PRP in the treatment of rotator cuff tears, osteoarthritis of the knee, ulnar collateral ligament tears, lateral epicondylitis, hamstring injuries, and Achilles tendinopathy.
ABSTRACT: BACKGROUND: Platelet-rich plasma (PRP) injections have become an intriguing treatment option for osteoarthritis (OA), particularly OA of the knee. Despite the plethora of PRP-related citations, there is a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded.
PURPOSE: To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma (ACP) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration (FDA).
STUDY DESIGN: Randomized controlled trial; Level of evidence, 1.
METHODS: In accordance with FDA protocol, patient selection was based on strict inclusion/exclusion criteria; 114 patients were screened, and 30 were ultimately included in the study. These patients were randomized to receive either ACP (n = 15) or saline placebo (n = 15) for a series of 3 weekly injections. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores served as the primary efficacy outcome measure. Patients were followed for 1 year.
RESULTS: No adverse events were reported for ACP administration. Furthermore, the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups. However, in the ACP group, WOMAC scores at 1 week were significantly decreased compared with baseline scores, and the scores for this group remained significantly lower throughout the study duration. At the study conclusion (12 months), subjects in the ACP group had improved their overall WOMAC scores by 78% from their baseline score, compared with 7% for the placebo group.
CONCLUSION: ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA. No adverse events were reported for ACP administration. After 1 year, WOMAC scores for the ACP subjects had improved by 78% from their baseline score, whereas scores for the placebo control group had improved by only 7%. Other joints affected with OA may also benefit from this treatment.
Journal»Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
<b>PURPOSE: </b>To compare the clinical and radiologic efficacy of adipose-derived stem cells (ADSCs) with fibrin glue and microfracture (MFX) versus MFX alone in patients with symptomatic knee cartilage defects.<b>METHODS: </b>Patients who were aged 18 to 50 years and had a single International Cartilage Repair Society grade III/IV symptomatic cartilage defect (≥3 cm(2)) on the femoral condyle were randomized to receive ADSCs with fibrin glue and MFX treatment (group 1, n = 40) or MFX treatment alone (group 2, n = 40). There was a lack of blinding for patients because of the additional intervention method (liposuction). The cartilage defect was diagnosed using preoperative magnetic resonance imaging (MRI), and quantitative and qualitative assessments of the repair tissue were carried out at 24 months by using the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system with follow-up MRI. Clinical results were evaluated using the Lysholm score, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and a 10-point visual analog scale for pain (0 points, no pain; 10 points, worst possible pain) preoperatively and postoperatively at 3 months, 12 months, and the last follow-up visit.<b>RESULTS: </b>The 2 groups had similar baseline patient characteristics. Follow-up MRI was performed at 24 months (mean, 24.3 months; range, 24.0 to 25.1 months) after the operation. Group 1 included 26 patients (65%) who had complete cartilage coverage of the lesion at follow-up compared with 18 patients (45%) in group 2. Significantly better signal intensity was observed for the repair tissue in group 1, with 32 patients (80%) having normal or nearly normal signal intensity (i.e., complete cartilage coverage of the lesion) compared with 28 patients (72.5%) in group 2. The mean clinical follow-up period was 27.4 months (range, 26 to 30 months). The improvements in the mean KOOS pain and symptom subscores were significantly greater at follow-up in group 1 than in group 2 (pain, 36.6 ± 11.9 in group 1 and 30.1 ± 14.7 in group 2 [P = .034]; symptoms, 32.3 ± 7.2 in group 1 and 27.8 ± 6.8 in group 2 [P = .005]). However, the improvements in the other subscores were not significantly different between group 1 and group 2 (activities of daily living, 38.5 ± 12.8 and 37.6 ± 12.9, respectively [P = .767]; sports and recreation, 33.9 ± 10.3 and 31.6 ± 11.0, respectively [P = .338]; quality of life, 38.4 ± 13.1 and 37.8 ± 12.0, respectively [P = .650]). Among the 80 patients, second-look arthroscopies were performed in 57 knees (30 in group 1 and 27 in group 2), and biopsy procedures were performed during these arthroscopies for 18 patients in group 1 and 16 patients in group 2. The second-look arthroscopies showed good repair tissue quality, although no significant intergroup difference was observed. The mean total histologic score was 1,054 for group 1 compared with 967 for group 2 (P = .036). Age, lesion size, duration of symptoms before surgery, mechanism of injury, and combined procedures were not correlated with clinical results, Magnetic Resonance Observation of Cartilage Repair Tissue scores, and histologic outcomes at short-term follow-up.<b>CONCLUSIONS: </b>Compared with MFX alone, MFX and ADSCs with fibrin glue provided radiologic and KOOS pain and symptom subscore improvements, with no differences in activity, sports, or quality-of-life subscores, in symptomatic single cartilage defects of the knee that were 3 cm(2) or larger, with similar structural repair tissue.<b>LEVEL OF EVIDENCE: </b>Level II, prospective comparative study.
This study was performed to compare the efficacy of treatment in three groups of patients with knee osteoarthritis (OA) given an intra-articular injection of platelet-rich plasma (PRP), hyaluronic acid (HA) or ozone gas.
METHODS:
A total of 102 patients with mild-moderate and moderate knee OA who presented at the polyclinic with at least a 1-year history of knee pain and VAS score ≥4 were randomly separated into three groups. Group 1 (PRP group) received intra-articular injection of PRP × 2 doses, Group 2 (HA group) received a single dose of HA, and Group 3 (Ozone group) received ozone × four doses. Weight-bearing anteroposterior-lateral and Merchant's radiographs of both knees were evaluated. WOMAC and VAS scores were applied to all patients on first presentation and at 1, 3, 6 and 12 months.
RESULTS:
At the end of the 1st month after injection, significant improvements were seen in all groups. In the 3rd month, the improvements in WOMAC and VAS scores were similar in Groups 1 and 2, while those in Group 3 were lower (p < 0.001). At the 6th month, while the clinical efficacies of PRP and HA were similar and continued, the clinical effect of ozone had disappeared (p < 0.001). At the end of the 12th month, PRP was determined to be both statistically and clinically superior to HA (p < 0.001).
CONCLUSION:
In the treatment of mild-moderate knee OA, PRP was more successful than HA and ozone injections, as the application alone was sufficient to provide at least 12 months of pain-free daily living activities.
