Corticosteroid injections for the treatment of osteoarthritis present a wide spectrum of effects ranging from detrimental to disease-modifying: A systematic review of preclinical evidence by the ESSKA Orthobiologic Initiative.

PURPOSE: Aim of this systematic review of preclinical evidence was to determine the effects of intra-articular corticosteroid (CS) injections in joints affected by osteoarthritis (OA). METHODS: A systematic review was performed on animal studies evaluating intra-articular CS injections for OA joints. The search was performed on PubMed, Cochrane, and Web of Science databases. A synthesis of the results was performed investigating CS effects by evaluating studies comparing CS with control groups. Morphological, histological, immunohistochemistry evaluations, clinical outcomes, biomarkers and imaging results were evaluated. The risk of bias was assessed according to the Systematic Review Centre for Laboratory Animal Experimentation's tool. RESULTS: Thirty-two articles analysing CS effects in OA animal models were included (1079 joints), 18 studies on small and 14 on large animals. CS injections showed overall positive effects in at least one of the outcomes in 68% of the studies, while 16% reported a deleterious effect. CS improved cartilage and synovial outcomes in 68% and 60% of the studies, but detrimental effects were documented in 11% and 20% of the studies, respectively. Clinical parameters evaluated in terms of pain, lameness or joint swelling improved in 63% of the studies but deteriorated in 13%. Evidence is limited on imaging and biomarkers results, as well as on the best CS type, dose, formulation and injection protocol. The risk of bias assessment revealed a 28% low and an 18% high risk of bias. CONCLUSION: Intra-articular CS injections induced a wide range of results on OA joints in experimental animal models, from disease-modifying and positive effects on pain and joint function at short-term evaluation to the lack of benefit or even negative effects. This underlines the need to identify more specific indications and treatment modalities to avoid possible detrimental effects while maximising the anti-inflammatory properties and the benefits of intra-articular CS in OA joints. LEVEL OF EVIDENCE: Level II.

Platelet-rich plasma augmentation in anterior cruciate ligament reconstruction: Evidence is still too scattered. A scoping review of randomised controlled trials.

PURPOSE: Platelet-rich plasma (PRP) augmentation has been proposed to improve the results of anterior cruciate ligament reconstruction (ACLR). The present study aims to quantify the available evidence to support the use of PRP as biological augmentation in ACLR surgery. METHODS: A systematic literature search was conducted on the PubMed, Cochrane, Web of Science and Embase databases on 10 March 2023. Inclusion criteria were randomised controlled trials (RCTs), written in English, addressing PRP augmentation in ACLR surgery, with no time limitation. A scoping review was performed to map the body of literature by examining the evidence related to specific aspects of patients' treatment and evaluation. Risk of bias evaluation was performed with the Cochrane risk-of-bias tool for randomised trials Version 2 (RoB 2), while the quality assessment was performed with the use of the Coleman Score. RESULTS: Out of 983 articles retrieved, 23 RCTs on 943 knees were included in this scoping review. PRP was administered in a liquid form in nine studies and clotted in 11 studies, while in three studies both liquid and clotted PRP were used. Hamstring auto/allografts were used in 14 studies, patellar tendon auto/allografts were used in eight studies and one study described ACLR with peroneus longus allografts. The map of the evidence documented high heterogeneity also in terms of surgical technique, objective and subjective outcome measures and radiological assessment, as well as follow-up times ranging from 1 day to 2 years, with virtually no overlapping data among studies neither in terms of treatments nor evaluations. Risk of bias evaluation showed an overall low quality of the included studies. CONCLUSIONS: The available literature addressing PRP augmentation in ACLR is largely scattered. PRP was produced and applied following different procedures, and high variability was detected across the included studies for every aspect of ACLR surgery and evaluation. Currently, a meaningful comparison of the available studies is not possible as the quantification of the literature results is biased by their heterogeneity. Future studies should provide more standardisation to investigate the benefits of biological augmentation in ACL surgery and confirm the promising yet weak evidence of PRP potential as well as the most suitable application modality, before routine use in clinical practice. LEVEL OF EVIDENCE: Levels I and II, scoping review.

Medial meniscal lesions increase antero-posterior laxity in knees with anterior cruciate ligament injury.

PURPOSE: The aim of this study was to quantify the impact of concomitant meniscal lesions on knee laxity using a triaxial accelerometer in a large population of patients affected by anterior cruciate ligament (ACL) injury. METHODS: A total of 326 consecutive patients (261 men and 65 women, mean age 31.3 ± 11.3) undergoing primary ACL reconstruction, were preoperatively evaluated through Lachman and pivot shift tests using a triaxial accelerometer to quantify knee laxity. An analysis based on the presence of meniscal tears assessed during surgery was performed to evaluate the impact of meniscal lesions on knee laxity. RESULTS: The anterior tibial translation (Lachman test) presented significantly higher values in patients with medial meniscal lesions (7.3 ± 1.7 mm, p = 0.049) and both medial and lateral meniscal lesions (7.7 ± 1.6 mm, p = 0.001) compared to patients without concomitant meniscal lesions (6.7 ± 1.3 mm). Moreover, patients with both medial and lateral meniscal lesions presented significantly higher values of anterior tibial translation compared to patients with lateral meniscal lesions (p = 0.049). No statistically significant differences were found between the groups in terms of tibial acceleration (pivot shift test). CONCLUSION: This study demonstrated that the contribution of concomitant meniscal lesions to knee laxity can be objectively quantified using a triaxial accelerometer in ACL-injured knees. In particular, medial meniscus lesions, alone or in association with lateral meniscus lesions, determine a significant increase of the anterior tibial translation compared to knees without meniscus tears. LEVEL OF EVIDENCE: Level IV.

Intra-articular corticosteroid injections provide a clinically relevant benefit compared to placebo only at short-term follow-up in patients with knee osteoarthritis: A systematic review and meta-analysis.

PURPOSE: To quantify the clinical relevance of intra-articular corticosteroid effects compared to placebo for the injective treatment of knee osteoarthritis (OA). METHODS: The PubMed, Cochrane Library and Web of Science databases were searched on May 3, 2023. This study was conducted in accordance with the PRISMA guidelines. The inclusion criteria were randomized controlled trials (RCTs), published in English, with no time limitation regarding publication date, comparing intra-articular corticosteroids and placebo injections for knee OA. The effects were quantified at short- (≤6 weeks), mid- (>6 weeks and ≤3 months), and long-term (≥6 months) follow-ups. The minimal clinically important difference (MCID) for the outcomes (visual analogue scale for pain - VAS: 1.4, Western Ontario and McMaster University Osteoarthritis Index - WOMAC: 9) was used to interpret the clinical improvement provided by intra-articular corticosteroid injections compared to placebo. The quality of each article was assessed using the Cochrane RoB 2 tool and the GRADE guidelines. RESULTS: Among the 1030 articles retrieved, 11 RCTs (842 patients) were included. A comparison of the two groups revealed statistically significant differences in the improvement of VAS and WOMAC scores in terms of the mean difference (MD); this difference was in favour of corticosteroids at short-term (p < 0.001, MD = -1.6 and p < 0.001, MD = -9.9, respectively) and mid-term follow-ups (p = 0.001, mean MD = -1.3 and p = 0.005, MD = -4.9, respectively). No difference was observed at the long-term follow-up. The MDs between the improvements in the two groups reached the MCID values for the VAS and WOMAC only at the short-term follow-up. The RoB 2 tool and the GRADE evaluations showed the presence of risk of bias and limited quality of evidence. CONCLUSION: This systematic review and meta-analysis demonstrated that intra-articular corticosteroid injections offer clinically perceivable pain relief and functional improvement higher than the placebo effect only at short-term follow-up in patients affected by knee OA, with benefits losing clinical relevance already after 6 weeks. These results, together with the low number and the limited quality of the RCTs comparing this treatment with placebo, question the indication for the use of corticosteroid injections in clinical practice for the treatment of knee OA. LEVEL OF EVIDENCE: Level I.

The reimbursement system can influence the treatment choice and favor joint replacement versus other less invasive solutions in patients affected by osteoarthritis.

PURPOSE: The aim of this study was to assess how physicians perceive the role of the reimbursement system and its potential influence in affecting their treatment choice in the management of patients affected by osteoarthritis (OA). METHODS: A survey was administered to 283 members of SIAGASCOT (Italian Society of Arthroscopy, Knee, Upper Limb, Sport, Cartilage and Orthopaedic Technologies), a National scientific orthopaedic society. The survey presented multiple choice questions on the access allowed by the current Diagnosis-Related Groups (DRG) system to all necessary options to treat patients affected by OA and on the influence toward prosthetic solutions versus other less invasive options. RESULTS: Almost 70% of the participants consider that the current DRG system does not allow access to all necessary options to best treat patients affected by OA. More than half of the participants thought that the current DRG system favors the choice of prosthetic solutions (55%) and that it can contribute to the increase in prosthetic implantation at the expense of less invasive solutions (54%). The sub-analyses based on different age groups, professional roles, and places of work allowed to evaluate the response in each specific category, confirming the findings for all investigated aspects. CONCLUSIONS: This survey documented that the majority of physicians consider that the reimbursement system can influence the treatment choice when managing OA patients. The current DRG system was perceived as unbalanced in favor of the choice of the prosthetic solution, which could contribute to the increase in prosthetic implantation at the expense of other less invasive options for OA management.

Intra-articular injections in sport-active patients with degenerative cartilage lesions or osteoarthritis of the knee: a systematic review.

PURPOSE: The aim of this systematic review was to analyse the available clinical evidence on intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis (OA) in sport-active patients. METHODS: A literature search was performed in July 2023 according to the PRISMA guidelines on three electronic databases (PubMed, Cochrane, Web of Science). Studies addressing intra-articular injections for degenerative knee cartilage lesions or knee OA in sport-active patients were included. The Downs and Black's "checklist for measuring quality" was used to evaluate risk of bias and quality of the included studies. RESULTS: Only 10 clinical studies for a total of 296 sport-active patients were included, with a publication trend increasing over time. The studies were 9 case series and 1 RCT; 7 studies focused on hyaluronic acid (HA), 2 studies focused on platelet-rich plasma (PRP), while 1 study compared HA and PRP. Overall, safety and positive clinical findings were for both HA and PRP, although not always with satisfactory results in terms of return to sport. The Downs and Black evaluation showed an overall poor quality of the included studies, with an average score of 21.1 points (range 19-25). CONCLUSIONS: The available clinical evidence is still limited, with only a few studies published and an overall low-quality of evidence, suggesting a potential role of HA and PRP injections to treat these patients. However, further high-level trials are needed to confirm the real benefits of these treatments for the management of sport-active patients affected by degenerative cartilage lesions or OA of the knee.

The 'placebo effect' in the conservative treatment of plantar fasciitis: a systematic review and meta-analyses.

Purpose: The study of the placebo effect is key to elucidate the 'real effect' of conservative interventions for plantar fasciitis. The aim of this meta-analysis was to quantify the impact of placebo in the different conservative treatments of plantar fasciitis. Methods: A systematic literature review was performed on double-blind placebo-controlled trials (RCTs) according to PRISMA guidelines on PubMed, Embase, and Web of Science. The meta-analysis primary outcome was the 0-10 pain variation after placebo treatments analyzed at 1 week, 1, 3, 6, and 12 months. The risk of bias was assessed using the RoB 2.0 tool, while the overall quality of evidence was graded according to the GRADE guidelines. Results: The placebo effect for conservative treatments was studied in 42 double-blind RCTs on 1724 patients. The meta-analysis of VAS pain showed a statistically significant improvement after placebo administration of 2.13/10 points (P < 0.001), being highest at 12 months with 2.79/10 points (P < 0.001). The improvement of the placebo groups was higher in the extracorporeal shock wave therapy studies compared to the injection studies (2.59 vs 1.78; P = 0.05). Eight studies had a low risk of bias, 23 studies had 'some concerns,' and 4 studies had a high risk of bias. The GRADE evaluation showed an overall high quality of evidence. Conclusion: This systematic review and meta-analysis demonstrated that the placebo effect represents an important component of all conservative approaches to treat plantar fasciitis. This effect is statistically and clinically significant, increases over time, and depends on the type of conservative treatment applied to address plantar fasciitis.

Adipose Tissue-Derived Products May Present Inflammatory Properties That Affect Chondrocytes and Synoviocytes from Patients with Knee Osteoarthritis.

Adipose tissue-derived cell-based injectable therapies have been demonstrated to have disease-modifying effects on joint tissues in preclinical studies on animal osteoarthritis (OA) models, but clinical results are heterogeneous and not always satisfactory. The aim of this study was to investigate the influence of adipose tissue properties on the therapeutic effects of the adipose-derived product in an in vitro OA setting. Micro-fragmented adipose tissue (MF-AT) samples were obtained from 21 OA patients (mean age 51.7 ± 11.8 years, mean BMI 25.7 ± 4.1 kg/m2). The analysis of the MF-AT supernatant was performed to analyze the release of inflammatory factors. The effects of MF-AT inflammatory factors were investigated on chondrocytes and synoviocytes gene expression levels. Patients' characteristics were analyzed to explore their influence on MF-AT inflammatory molecules and on the MF-AT effects on the gene expression of chondrocytes and synoviocytes. The study results demonstrated that adipose tissue-derived products may present inflammatory properties that influence the therapeutic potential for OA treatment, with products with a higher pro-inflammatory profile stimulating a higher expression of genes related to a more inflamed and catabolic phenotype. A higher pro-inflammatory cytokine pattern and a higher pro-inflammatory effect were found in adipose tissue-derived products obtained from OA patients with higher BMI.

Hyaluronic scaffold transplantation with bone marrow concentrate for the treatment of osteochondral lesions of the talus: durable results up to a minimum of 10 years.

PURPOSE: The aim of this study was to evaluate the long-term clinical results of the transplantation of a hyaluronic acid membrane augmented with bone marrow aspirate concentrate (BMAC) in an one-step technique for the treatment of patients affected by osteochondral lesions of the talus (OLT). METHODS: A total of 101 patients (64 men, 37 women, age 32.9 ± 10.9) were evaluated for a minimum of 10 years of follow-up (151.5 ± 18.4 months) The mean lesion size was 2.2 ± 1.4 cm2, the lesion had a post-traumatic origin in 73 patients, 15 patients previously had an ankle fracture, 22 patients had ankle osteoarthritis. All patients were clinically evaluated at baseline and at 2, 5, and a minimum of 10 years after treatment using the AOFAS score, the NRS for pain, and the Tegner score. A survival analysis was performed to check the survival to failure up to the last follow-up. RESULTS: The AOFAS score significantly improved from baseline (59.6 ± 13.9) to the final follow-up (82.3 ± 14.2) (p < 0.0005). A significant reduction in the AOFAS score was found from 2 to 10 years (p < 0.0005). The NRS for pain changed from 7.0 ± 1.3 at baseline to 3.9 ± 2.7 at the final follow-up (p < 0.0005). A significant worsening was documented between 5 years and the final follow-up (p < 0.0005). The Tegner score improved from the preoperative value of 2.0 (range 1-7) to 3.0 (range 1-7) at the final follow-up (p < 0.0005), although it remained lower as compared to the preinjury level of 4.0 (range 1-9) (p < 0.0005). Better results were documented in male and younger patients with smaller lesions, without the previous surgery, and without the previous ankle fractures or osteoarthritis. At the final follow-up, 85 patients considered their general health status "satisfactory" and 84 patients reported feeling "better" than the preoperative condition. Five patients were considered failures and underwent prosthetic ankle replacement or repeated the same surgery. CONCLUSION: This one-step technique showed to be an effective procedure for the treatment of OLT, providing a low failure rate and offering durable clinical improvements up to a minimum of 10 years of follow-up. However, this technique demonstrated a small yet significant decrease over the years in terms of pain and function and poor results in terms of sports activity level. LEVEL OF EVIDENCE: Level IV.

Joint Response to Exercise Is Affected by Knee Osteoarthritis: An Infrared Thermography Analysis.

Infrared thermography can be used to evaluate the inflammation characterizing the joint environment of OA knees, but there is limited evidence on the response to physical exercise. Identifying the response to exercise of OA knees and the influencing variables could provide important information to better profile patients with different knee OA patterns. Sixty consecutive patients (38 men/22 women, 61.4 ± 9.2 years) with symptomatic knee OA were enrolled. Patients were evaluated with a standardized protocol using a thermographic camera (FLIR-T1020) positioned at 1 m with image acquisition of an anterior view at baseline, immediately after, and at 5 min after a 2-min knee flexion-extension exercise with a 2 kg anklet. Patients' demographic and clinical characteristics were documented and correlated with the thermographic changes. This study demonstrated that the temperature response to exercise in symptomatic knee OA was affected by some demographic and clinical characteristics of the assessed patients. Patients with a poor clinical knee status presented with a lower response to exercise, and women showed a greater temperature decrease than men. Not all evaluated ROIs showed the same trend, which underlines the need to specifically study the different joint subareas to identify the inflammatory component and joint response while investigating knee OA patterns.

Infrared Thermography in Symptomatic Knee Osteoarthritis: Joint Temperature Differs Based on Patient and Pain Characteristics.

The aim of this study was to evaluate osteoarthritis (OA) patients with infrared thermography to investigate imaging patterns as well as demographic and clinical characteristics that influence knee inflammation. Forty patients with one-sided symptomatic knee OA were included and evaluated through knee-specific PROMs and the PainDETECT Questionnaire for neuropathic pain evaluation. Thermograms were captured using a thermographic camera FLIR-T1020 and temperatures were extracted using the software ResearchIR for the overall knee and the five ROIs: medial, lateral, medial patella, lateral patella, and suprapatellar. The mean temperature of the total knee was 31.9 ± 1.6 °C. It negatively correlated with age (rho = -0.380, p = 0.016) and positively correlated with BMI (rho = 0.421, p = 0.007) and the IKDC objective score (tau = 0.294, p = 0.016). Men had higher temperatures in the knee medial, lateral, and suprapatellar areas (p = 0.017, p = 0.019, p = 0.025, respectively). Patients with neuropathic pain had a lower temperature of the medial knee area (31.5 ± 1.0 vs. 32.3 ± 1.1, p = 0.042), with the total knee negatively correlating with PainDETECT (p = 0.045). This study demonstrated that the skin temperature of OA symptomatic knees is influenced by demographic and clinical characteristics of patients, with higher joint temperatures in younger male patients with higher BMI and worst objective knee scores and lower temperatures in patients affected by neuropathic pain.

The Minimal Clinically Important Difference Changes Greatly Based on the Different Calculation Methods.

BACKGROUND: The minimal clinically important difference (MCID) for patient-reported outcome measures (PROMs) expresses both the extent of the improvement and the value that patients place on it. MCID use is becoming increasingly widespread to understand the clinical efficacy of a given treatment, define guidelines for clinical practice, and properly interpret trial results. However, there is still large heterogeneity in the different calculation methods. PURPOSE: To calculate and compare the MCID threshold values of a PROM by applying various methods and analyzing their effect on the study results interpretation. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 3. METHODS: The data set used to investigate the different MCID calculation approaches was based on a database of 312 patients affected by knee osteoarthritis and treated with intra-articular platelet-rich plasma. MCID values were calculated on the International Knee Documentation Committee (IKDC) subjective score at 6 months using 2 approaches: 9 methodologies referred to an anchor-based approach and 8 methodologies to a distribution-based approach. The obtained threshold values were applied to the same series of patients to understand the effect of using different MCID methods in evaluating patient response to treatment. RESULTS: The different methods employed led to MCID values ranging from 1.8 to 25.9 points. The anchor-based methods ranged from 6.3 to 25.9, while the distribution-based ones were from 1.8 to 13.8 points, showing a 4.1× variation of the MCID values within the anchor-based methods and a 7.6× variation within the distribution-based methods. The percentage of patients who reached the MCID for the IKDC subjective score changed based on the specific calculation method used. Among the anchor-based methods, this value varied from 24.0% to 66.0%, while among the distribution-based methods, the percentage of patients reaching the MCID varied from 44.6% to 75.9%. CONCLUSION: This study proved that different MCID calculation methods lead to highly heterogeneous values, which significantly affect the percentage of patients achieving the MCID in a given population. The wide-ranging thresholds obtained with the different methodologies make it difficult to evaluate the real effectiveness of a given treatment questioning the usefulness of MCID, as currently available, in the clinical research.

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 2: bone marrow-derived cell-based injectable therapies.

PURPOSE: Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by osteoarthritis (OA) in animal models. METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical animal studies comparing injectable bone marrow-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool. RESULTS: Fifty-three studies were included (1819 animals) with an increasing publication trend over time. Expanded cells were used in 48 studies, point-of-care products in 3 studies, and both approaches were investigated in 2 studies. Among the 47 studies presenting results on the disease-modifying effects, 40 studies (85%) reported better results with bone marrow-derived products compared to OA controls, with positive findings evident in 14 out of 20 studies (70%) in macroscopic assessment, in 30 out of 41 studies (73%) in histological assessment, and in 10 out of 13 studies (77%) in immunohistochemical evaluations. Clinical evaluations showed positive results in 7 studies out of 9 (78%), positive imaging results in 11 studies out of 17 (65%), and positive biomarker results in 5 studies out of 10 (50%). While 36 out of 46 studies (78%) reported positive results at the cartilage level, only 3 out of 10 studies (30%) could detect positive changes at the synovial level. The risk of bias was low in 42% of items, unclear in 50%, and high in 8%. CONCLUSION: This systematic review of preclinical studies demonstrated that intra-articular injections of bone marrow-derived products can induce disease-modifying effects in the treatment of OA, slowing down the progression of cartilage damage with benefits at macroscopic, histological, and immunohistochemical levels. Positive results have been also observed in terms of clinical and imaging findings, as well as in the modulation of inflammatory and cartilage biomarkers, while poor effects have been described on the synovial membrane. These findings are important to understand the potential of bone marrow-derived products and to guide further research to optimise their use in the clinical practice. LEVEL OF EVIDENCE: II.

Infection Risk Increases After Total Hip Arthroplasty Within 3 Months Following Intra-Articular Corticosteroid Injection. A Meta-Analysis on Knee and Hip Arthroplasty.

BACKGROUND: Much debate continues regarding the risk of postoperative infection after intra-articular corticosteroid injection prior to total joint arthroplasty. The aim of this study was to evaluate the risk of periprosthetic joint infection (PJI) or other complications after joint arthroplasty in patients who received preoperative corticosteroids injections. METHODS: A literature search was performed on PubMed, Web of Science, and Cochrane Library through January 4, 2022. Of 4,596 studies, 28 studies on 480,532 patients were selected for qualitative analysis. Studies describing patients receiving corticosteroids injections before joint arthroplasty (hip, knee) were included in the systematic review. A meta-analysis was performed of studies focusing on corticosteroids injections and PJI. Assessment of risk of bias and quality of evidence was based on the "Downs and Black's Checklist for Measuring Quality". RESULTS: A significant association (odds ratio: 1.55, P = .001, 95% confidence interval: 1.357-1.772) between PJI and corticosteroids injections was found for total hip arthroplasty (THA). No association was found for knee arthroplasty procedures. The risk of PJI is statistically higher (odds ratio: 1.20, P = .045, 95% confidence interval: 1.058-1.347) if the injections are performed within 3 months preoperatively in THA patients. CONCLUSION: Patients undergoing THA who previously received intra-articular injections of corticosteroids may expect a statistically higher risk of developing PJI. On the contrary, no association between corticosteroids injections and PJI could be seen in total knee arthroplasty patients. In addition, injection timing plays an important role: surgeons should refrain from administering corticosteroids injections within 3 months before hip arthroplasty, as it appears to be less safe than waiting a 3-month interval.

Platelet-rich plasma does not improve clinical results in patients with rotator cuff disorders but reduces the retear rate. A systematic review and meta-analysis.

PURPOSE: To assess whether the use of Platelet-rich plasma (PRP) produces a clinical benefit in patients with rotator cuff disorders, treated either conservatively or surgically. METHODS: A systematic review was performed according to PRISMA guidelines on three databases (PubMed, Cochrane Library, Web of Science) to identify randomised controlled trials (RCTs) on the use of PRP in patients with rotator cuff disorders, treated either conservatively or surgically. A meta-analysis was performed on articles reporting results for Constant, UCLA, VAS, SST scores and retear rate. The RoB 2.0 and the modified Coleman Methodology Score were used to assess methodological quality. RESULTS: A total of 36 RCTs (20 surgical, 16 conservative) were included, for a total of 2,443 patients. Conservative treatment showed high heterogeneity and no clear consensus in favour of PRP. The meta-analysis of the studies with surgical treatment showed no benefit in using PRP in any of the clinical outcomes, either at the short or medium/long-term follow-up. However, the retear rate was lower with PRP augmentation (p < 0.001). The overall quality of the studies was moderate to high, with the surgical studies presenting a lower risk of bias than the conservative studies. CONCLUSION: The use of PRP as augmentation in rotator cuff surgical repair significantly reduces the retear rate. However, no benefits were documented in terms of clinical outcomes. PRP application through injection in patients treated conservatively also failed to present any clear advantage. While there are many studies in the literature with several RCTs of moderate to high quality, the high heterogeneity of products and studies remains a significant limitation to fully understanding PRP potential in this field. LEVEL OF EVIDENCE: Level I.

Bone marrow aspirate concentrate quality is affected by age and harvest site.

PURPOSE: To compare the number and properties of bone marrow stromal cells (BMSCs) collected from bone marrow aspirate concentrate (BMAC) obtained from different harvest sites and from patients of different ages. METHODS: BMAC was obtained from two groups of patients based on age (n = 10 per group): 19.0 ± 2.7 years for the younger and 56.8 ± 12.5 for the older group. In the latter, BMAC was obtained from both iliac crest and proximal tibia for a donor-matched analysis. Mononucleated cell count and CFU-F assay were performed, together with phenotype characterization of BMSCs from iliac crest and proximal tibia, the study of chondrogenic and osteogenic differentiation capacity, histological staining and spectrophotometric quantification, and the analysis of mRNAs expression. RESULTS: Cells derived from iliac crest and proximal tibia showed the same phenotypic pattern at flow cytometry, as well as similar chondrogenic and osteogenic potential. However, a significantly higher number of mononuclear cells per ml was observed in younger patients (3.8 ± 1.8 × 107) compared to older patients (1.2 ± 0.8 × 107) (p < 0.0005). The latter yield, obtained from the iliac crest, was significantly higher than resulting from the BMAC harvested from the proximal tibia in the same group of patients (0.3 ± 0.2 × 107, p < 0.0005). This result was confirmed by the CFU-F analysis at day 10 (15.9 ± 19.4 vs 0.6 ± 1.0, p = 0.001) and day-20 (21.7 ± 23.0 vs 2.9 ± 4.2, p = 0.006). CONCLUSION: Harvest site and age can affect the quality of BMAC. BMSCs obtained from iliac crest and proximal tibia present comparable mesenchymal markers expression as well as osteogenic and chondrogenic differentiation potential, but iliac crest BMAC presents a four times higher number of mononucleated cells with significantly higher clonogenic capacity compared to the tibia. BMAC of younger patients also had a three-time higher number of mononucleated cells. The identification of BMAC characteristics could help to optimize its preparation and to identify the most suitable indications for this orthobiologic treatment in the clinical practice.

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies.

PURPOSE: The aim of this systematic review was to determine if adipose tissue-derived cell-based injectable therapies can induce disease-modifying effects in joints affected by osteoarthritis (OA). METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical studies comparing injectable adipose-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool. RESULTS: Seventy-one studies were included (2,086 animals) with an increasing publication trend over time. Expanded cells were used in 65 studies, 3 studies applied point of care products, and 3 studies investigated both approaches. Overall, 48 out of 51 studies (94%) reported better results with adipose-derived products compared to OA controls, with positive findings in 17 out of 20 studies (85%) in macroscopic, in 37 out of 40 studies (93%) in histological, and in 22 out of 23 studies (96%)  in immunohistochemical evaluations. Clinical and biomarker evaluations showed positive results in 14 studies out of 18 (78%) and 12 studies out of 14 (86%), while only 9 studies out of 17 (53%) of the imaging evaluations were able to detect differences versus controls. The risk of bias was low in 38% of items, unclear in 51%, and high in (11%). CONCLUSION: The current preclinical models document consistent evidence of disease-modifying effects of adipose-derived cell-based therapies for the treatment of OA. The high heterogeneity of the published studies highlights the need for further targeted research to provide recommendations on the optimal methodologies for a more effective application of these injective therapies for the treatment of OA in clinical practice. LEVEL OF EVIDENCE: II.