Subchondroplasty® (SCP) Provides Resolution of Symptoms and Functional Improvements in Mild-to-Moderate Knee Osteoarthritis with Persistent Bone Marrow Lesions: 12-Month Follow-Up Results from a Multicentric Open-Label Prospective Clinical Trial.

Introduction. Bone marrow lesions (BMLs) are MRI-visible subchondral bone alterations, highly correlated with symptoms in the knee. Subchondroplasty (SCP) is able to fill the subchondral defects associated with BMLs using an injectable bone substitute material. The aim of the present study is to evaluate the 12-month outcomes of the SCP in the treatment of symptoms of mild-to-moderate knee osteoarthritis (OA) patients with persistent BMLs of the knee. Materials and Methods. Subjects affected by BMLs of the femoral condyle or tibial plateau that were present for >3 months and not responsive to conservative treatments were enrolled in this prospective multicenter trial. All the patients underwent SCP. Follow-up was conducted at 1, 3, 6 and 12 months. All subjects completed Numerical Rating Scale (NRS) for pain, Knee Injury and Osteoarthritis Outcome (KOOS) score, Euro Quality of life-5 dimensions (EQ-5D) score, and a subject global satisfaction scale. Demographic information of the patients was also collected. Results. A total of 79 patients completed the 12-month follow-up. Statistically significant improvements on all clinical scales were registered from baseline to the 12-month follow-up. No severe adverse events were reported. Four patients were considered failed. A 12-month subgroup analysis was performed to evaluate the possible correlation between all the KOOS subscales and age, gender, number of BMLs, location of BMLs, and Kellgren-Lawrence grade: no statistically significant associations were observed. Conclusion. SCP is a safe and effective procedure for the treatment of symptoms related to persisting BMLs in mild-to-moderate osteoarthritic knees, with a low failure rate up to 12 months' evaluation.

No Significant Differences between Bisphosphonates and Placebo for the Treatment of Bone Marrow Lesions of the Knee: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: The purpose of the present systematic review and meta-analysis is to summarize the current evidence on the role of bisphosphonates in the treatment of knee bone marrow lesions (BMLs), to understand whether they are truly effective in improving symptoms and restoring the subchondral bone status at imaging evaluation. Methods: A literature search was carried out on PubMed, Cochrane, and Google Scholar databases in accordance with the PRISMA guidelines. Potential risk of bias was evaluated using the Cochrane Risk of Bias 2 tool for randomized controlled trials (RCTs) and the ROBINS-I tool for non-randomized studies. Results: A total of 15 studies were included in the present systematic review and meta-analysis. Seven studies were RCTs, two were prospective cohort studies, three were retrospective, and three were case series. Our meta-analysis revealed that bisphosphonates did not significantly improve clinical scores or reduce BML size compared to placebo. Accordingly, the rate of adverse events was also non-significantly higher among bisphosphonate users versus placebo users. Conclusions: The main finding of the present meta-analysis and systematic review is that bisphosphonates show neither significant benefits nor significant adverse events when compared to placebo in the treatment of BMLs of the knee. Level of Evidence: Level IV systematic review of level II-III-IV studies. Level I meta-analysis of level I studies.

Preliminary osteogenic and antibacterial investigations of wood derived antibiotic-loaded bone substitute for the treatment of infected bone defects.

Introduction: The development of reliable treatments for infected or potentially infected bone loss resulting from open fractures and non-unions is extremely urgent, especially to reduce the prolonged courses of antimicrobial therapy to which affected patients are subjected. Numerous bone graft substitutes have been used over the years, but there are currently no effective solutions to treat critical bone loss, especially in the presence of infection. The present study evaluated the use of the biomorphic calcium phosphate bone scaffold b. Bone™, based on a next-generation resorbable biomimetic biomaterial, in bone reconstruction surgery in cases of infection. Methods: Using an "in vitro 3D bone fracture model" to predict the behavior of this drug delivery system during critical bone loss at an infected (or potentially infected) site, the effects of scaffolds loaded with gentamicin or vancomycin on the viability and differentiation capacity of human mesenchymal stem cells (hMSCs) were evaluated. Results: This scaffold, when loaded with gentamicin or vancomycin, exhibits a typical drug release curve that determines the inhibitory effects on the growth of Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli, as well as relative biofilm formation. Discussion: The study demonstrates that b.bone scaffolds can effectively address key challenges in orthopedic surgery and patient care by inhibiting bacterial growth and biofilm formation through rapid, potent antibiotic release, reducing the risk of treatment failure due to resistance, and providing a promising solution for bone infections and improved patient outcomes. Future studies could explore the combination of different antibiotics on these scaffolds for more tailored and effective treatments against post-traumatic osteomyelitis pathogens.

The chimera of reaching a universal consensus on platelet-rich plasma treatment for knee osteoarthritis: a review of recent consensus statements and expert opinion.

INTRODUCTION: Osteoarthritis (OA) is a prevalent cause of disability worldwide, affecting millions and posing significant socioeconomic burdens. Various conservative measures like hyaluronic acid (HA) and platelet-rich plasma (PRP) injections aim to manage OA symptoms and delay surgical interventions. Despite the increasing utilization of PRP, consensus on its efficacy remains elusive, reflecting the evolving landscape of OA management. AREAS COVERED: This study reviews guidelines and recommendations on intra-articular PRP injections for OA globally, highlighting divergent perspectives among different medical societies. A comprehensive literature search identified 19 relevant guidelines, indicating a temporal and geographic evolution in attitudes toward PRP use. While some guidelines endorse PRP for mild-to-moderate OA, others express caution due to concerns about product standardization and clinical evidence heterogeneity. EXPERT OPINION: The lack of universal consensus on PRP for OA underscores the complex interplay between clinical evidence, practice patterns, and evolving perspectives. Recent shifts toward endorsing PRP may reflect advancements in preparation techniques and personalized medicine approaches. However, challenges persist, including patient selection and product standardization. Efforts to develop consensus and refine PRP classification systems are essential for guiding clinical practice and advancing OA management.

The Trochlear Bisector as a New Landmark for Kinematic Alignment in Total Knee Arthroplasty: A Radiographic Study.

Background: In recent years, there has been considerable interest in prosthetic alignment techniques for total knee arthroplasty (TKA), particularly in the so-called kinematic alignment, which aims to restore the knee's native alignment. However, implementing this technique requires specialized instruments and procedural steps that can be laborious. This study introduces the bisector of the trochlear groove as a reliable landmark for performing the distal femoral cut while maintaining parallelism with the native femoral joint line. Methods: Three orthopedic specialists assessed 110 X-ray images of full-leg, weight-bearing lower limbs obtained from healthy individuals between January 2021 and December 2022. The bisector of the trochlear groove was identified on the X-ray images, and the angle between this bisector and the femoral joint line was measured. The consistency of these measurements across repeated assessments and different examiners was evaluated. Results: The bisector of the trochlear groove was found to be perpendicular to the femoral joint line, with a mean angle of 89.4°. The inter-rater reliability was 68% within ±1.3° from the mean, while the intra-rater reliability was 82% within ±1.5° from the mean. Conclusions: These results suggest that by performing a femoral cut perpendicular to the bisector of the trochlear groove, surgeons can inherently restore the femoral joint line of the native knee in patients where the native joint line is no longer identifiable due to the effect of osteoarthritis. This method may offer a viable and straightforward alternative to the standard surgical technique currently practiced for kinematic alignment in TKA.

Conservative Treatment for Ankle Cartilage: Cellular and Acellular Therapies: A Systematic Review.

Biological agents like growth factors (ie, platelet rich plasma) and mesenchymal stem cells are rising in popularity among orthopedics. Orthobiologics therapy aims to fill the gap between conventional conservative therapies like hyaluronic acid and surgery, especially for cartilage disease. Ankle cartilage defects are very symptomatic and could lead to a severe decrease of quality of life in patients, because of pain, swelling, and inability to walk without pain. In this scenario, this paper aims to systematically review the current literature available about biological therapies for ankle cartilage.

Safety and Efficacy of Hybrid Cooperative Complexes of Sodium Hyaluronate and Sodium Chondroitin for the Treatment of Patients with Symptomatic Knee Osteoarthritis.

INTRODUCTION: Knee osteoarthritis (KOA) represents a widespread degenerative disease that causes pain and motor disability. Conservative treatments mainly focus on relieving symptoms, improving joint function, and trying to delay surgery. Safety and efficacy of hybrid cooperative complexes (2.4% sodium hyaluronate and 1.6% sodium chondroitin; HA-SC) for symptomatic KOA were investigated in a single-arm, prospective, pilot study. METHODS: Patients with a visual analogue scale (VAS) pain score ≥ 4 and Kellgren-Lawrence Grade < 4 received a single intraarticular HA-SC injection. Patients with a VAS score change from baseline ≤ 1 received a second injection at day 30. Device-related adverse events (DR-AEs)/adverse events (AEs) were primary endpoints. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis Index LK 3.1 (WOMAC LK 3.1), VAS, patient global assessment of disease status (PtGA), and patient proportion needing a second injection. RESULTS: Of 83 patients with KOA (Kellgren-Lawrence Grade, 2-3), 34.9% had DR-AEs at day 7. No serious DR-AEs/AEs were reported. A significant (P < 0.0001) reduction over time in VAS pain score plus WOMAC pain, stiffness, physical function limitation, and total scores was reported. Median PtGA scores indicated a 'slight improvement' at most follow-up visits. Only 18.1% of patients required a second injection. CONCLUSIONS: A single intraarticular HA-SC injection was safe, well-tolerated, and did not lead to major deterioration in terms of reducing knee pain, stiffness, and physical function limitation in patients with symptomatic KOA.

Early application of extracorporeal shock wave therapy improves pain control and functional scores in patients undergoing total knee arthroplasty: a randomized controlled trial.

PURPOSE: The use of biophysical stimuli produced by extracorporeal shock wave therapy (ESWT) can improve the rehabilitation treatment of patients undergoing total knee arthroplasty (TKA). The aim of our study is to evaluate the short-term efficacy of early postoperative ESWT in combination with physiotherapy in terms of pain reduction and motor function recovery of patients undergoing TKA and compare it with conventional physiotherapy treatment. METHODS: Fifty-six patients undergoing TKA were enrolled in the study from January 2019 to February 2020. Patients received two sessions of physiotherapy daily, with (experimental group) or without (control group) four sessions of ESWT within seven days after surgery. Patients were prospectively evaluated at baseline and at post-operative day two and seven. Assessment included active knee range of motion (aROM), timed up and go (TUG) test, visual analogue scale (VAS) for pain, and Borg scale. RESULTS: Fifty patients completed the study. Both treatments proved to be effective in reducing pain and improving the knee range of motion and functional scores at seven days after surgery: the aROM in the ESWT group was 36.8 ± 11.0 grades (p < 0.001), while in control group was 19.8 ± 7.8 grades (p < 0.001). TUG, VAS, and BORG scores showed a similar trend. Comparative analysis revealed superior clinical results for the experimental group in all the outcomes, in particular aROM (96.0 ± 5.40 vs. 81.20 ± 11.01, p < 0.001) and TUG test (17.4 ± 5.61 vs. 21.24 ± 5.88, p < 0.001), at day seven after surgery. CONCLUSION: Early application of ESWT in addition to physiotherapy can positively influence the rehabilitation process after TKA. The treatment proved to be well tolerated and safe. Preliminary results demonstrated better pain control and functional scores compared to physiotherapy alone.

The role of WNT and IL-1 signaling in osteoarthritis: therapeutic implications for platelet-rich plasma therapy.

Different from inflammatory arthritis, where biologicals and targeted synthetic molecules have revolutionized the disease course, no drug has demonstrated a disease modifying activity in osteoarthritis, which remains one of the most common causes of disability and chronic pain worldwide. The pharmacological therapy of osteoarthritis is mainly directed towards symptom and pain relief, and joint replacement is still the only curative strategy. Elucidating the disease pathophysiology is essential to understand which mechanisms can be targeted by innovative therapies. It has extensively been demonstrated that aberrant WNT and IL-1 signaling pathways are responsible for cartilage degeneration, impaired chondrocyte metabolism and differentiation, increased extracellular matrix degradation, and altered subchondral bone homeostasis. Platelet-rich plasma is an autologous blood derivative containing a concentration of platelets that is much higher than the whole blood counterpart and has shown promising results in the treatment of early knee osteoarthritis. Among the proposed mechanisms, the modulation of WNT and IL-1 pathways is of paramount importance and is herein reviewed in light of the proposed regenerative approaches.

Ozone Therapy versus Hyaluronic Acid Injections for Pain Relief in Patients with Knee Osteoarthritis: Preliminary Findings on Molecular and Clinical Outcomes from a Randomized Controlled Trial.

Ozone therapy (OT) is used for the treatment of multiple musculoskeletal disorders. In recent years, there has been a growing interest in its use for the treatment of osteoarthritis (OA). The aim of this double-blind randomized controlled trial was to evaluate the efficacy of OT compared with hyaluronic acid (HA) injections for pain relief in patients with knee OA. Patients with knee OA for at least three months were included and randomly assigned to receive three intra-articular injections of ozone or HA (once a week). Patients were assessed at baseline and at 1, 3, and 6 months after the injections for pain, stiffness, and function using the WOMAC LK 3.1, the NRS, and the KOOS questionnaire. Out of 55 patients assessed for eligibility, 52 participants were admitted to the study and randomly assigned into the 2 groups of treatment. During the study, eight patients dropped out. Thus, a total of 44 patients, reached the endpoint of the study at 6 months. Both Group A and B consisted of 22 patients. At 1-month follow-up after injections, both treatment groups improved statistically significantly from baseline in all outcomes measured. At 3 months, improvements remained similarly consistent for Group A and Group B. At 6-month follow-up, the outcomes were comparable between the 2 groups, showing only a worsening trend in pain. No significant differences were found between the two groups in pain scores. Both therapies have proven to be safe, with the few recorded adverse events being mild and self-limiting. OT has demonstrated similar results to HA injections, proving to be a safe approach with significant effects on pain control in patients affected by knee OA. Due to its anti-inflammatory and analgesic effects, ozone might be considered as a potential treatment for OA.

Placenta-Derived Products Demonstrate Good Safety Profile and Overall Satisfactory Outcomes for Treating Knee Osteoarthritis: A Systematic Review of Clinical Evidence.

PURPOSE: To summarize the available evidence regarding the clinical application of placenta-derived products to treat knee osteoarthritis (OA), underlining the differences existing among products, their preparation methods, and the clinical results reported so far. METHODS: A research on PubMed, Cochrane, and Google Scholar databases was performed. The following inclusion criteria for relevant articles were used: (1) randomized controlled trials (RCTs), prospective and retrospective studies, on humans; (2) written in English; (3) published in indexed journals in the last 10 years (2011-2022); and (4) dealing with the use of placenta-derived products for the treatment of knee OA. Exclusion criteria were articles written in other languages; animals or in vitro trials; reviews; and trials analyzing other applications of placenta-derived products not related to knee OA. RESULTS: In total, 16 studies were included in the present systematic review. Five studies investigated placenta-derived products as an augmentation during surgical procedures, whereas 11 studies were focused on the injective approach only. Of these, only 4 were RCTs and were all from the injective approach group. Potential risk of bias was carried out using Cochrane Risk of Bias 2 tool for RCTs and a modified Coleman approach for nonrandomized studies, revealing for both an overall insufficient quality. Clinical outcomes reveal excellent safety profile and notable efficacy, despite the different types of products used and different administration methods adopted. CONCLUSIONS: Placental products showed a good safety profile and overall satisfactory outcomes for the treatment of knee OA. LEVEL OF EVIDENCE: Level IV, systematic review of Level II, III and IV studies.

Aragonite-Based Scaffold Versus Microfracture and Debridement for the Treatment of Knee Chondral and Osteochondral Lesions: Results of a Multicenter Randomized Controlled Trial.

BACKGROUND: Lesions of the articular cartilage, with or without involvement of the subchondral bone, are a common cause of pain and dysfunction in the knee. Although several treatment options have been developed, the majority of previous clinical trials examined patients with isolated or focal midsized defects, which rarely represent the condition found in the general population. Rather, cartilage lesions are often associated with the presence of mild to moderate osteoarthritic changes. PURPOSE: The present multicenter randomized controlled trial compared the clinical and radiographic outcomes of an aragonite-based osteochondral implant with a control group (arthroscopic debridement/microfractures) in patients affected by joint surface lesions of the knee, including those with concurrent mild to moderate osteoarthritis. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 251 patients were enrolled in 26 medical centers according to the following criteria: age 21 to 75 years, up to 3 cartilage defects of International Cartilage Regeneration & Joint Preservation Society grade 3a or above located on the femoral condyles and/or trochlea, total treatable area from 1 to 7 cm2, bony defect depth ≤8 mm, and knee osteoarthritis grade 0 to 3 according to Kellgren-Lawrence score. Patients were randomized to the aragonite-based implant or debridement/microfracture control arm in a 2:1 ratio. Evaluation was performed at 6, 12, 18, and 24 months based on overall Knee injury and Osteoarthritis Outcome Score (KOOS) as the primary endpoint, and the KOOS subscales (Pain, Quality of Life, Activities of Daily Living), percentage of responders, and International Knee Documentation Committee (IKDC) subjective score as the secondary endpoints. Patients also underwent magnetic resonance imaging evaluation at 12 and 24 months to assess defect fill grade. Failures (ie, need for any secondary treatment) and adverse events were also recorded. RESULTS: The implant group showed a statistically superior outcome in the primary endpoint and all secondary endpoints at each follow-up. The magnitude of improvement in the implant group was twice as large as that in the control group in terms of mean KOOS improvement at 2 years. Responder rate (defined as at least a 30-point improvement in overall KOOS) was 77.8% in the implant group as opposed to 33.6% in the control (P < .0001). Statistically superior results were seen in the IKDC score as well. At 24 months, 88.5% of the implanted group had at least 75% defect fill on magnetic resonance imaging as compared with 30.9% of controls (P < .0001). The failure rate was 7.2% for the implant group versus 21.4% for control. CONCLUSION: This aragonite-based scaffold was safe and effective in the treatment of chondral and osteochondral lesions in the knee, including patients with mild to moderate osteoarthritis, and provided superior outcomes as compared with the control group. REGISTRATION: NCT03299959 (ClinicalTrials.gov identifier).

Intra-Articular Injection of Botulinum Toxin for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials.

The purpose of the present paper was to review the available evidence on intra-articular botulinum toxin (BTX) injection in the treatment of knee osteoarthritis and to compare it to other conservative treatment options. A systematic review of the literature was performed on the PubMed, Scopus, Cochrane Library, Web of Science, Pedro and Research Gate databases with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) written in the English language, and (3) published on indexed journals in the last 20 years (2001-2021) dealing with the use of BTX intra-articular injection for the treatment of knee OA. The risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. Nine studies involving 811 patients in total were included. Patients in the control groups received different treatments: conventional physiotherapy, hyaluronic acid injection or prolotherapy or a combination thereof in 5 studies, steroid infiltrative therapy (triamcinolone) in 1 study, placebo in 2, and local anesthetic treatment in 1 study. Looking at the quality of the available literature, two of the included studies reached "Good quality" standard, three were ranked as "Fair", and the rest were considered "Poor". No major complications or serious adverse events were reported following intra-articular BTX, which provided encouraging pain relief, improved motor function, and quality of life. Based on the available data, no clear indication emerged from the comparison of BTX with other established treatments for knee OA. The analysis of the available RCTs on BTX intra-articular injection for the treatment of knee OA revealed modest methodological quality. However, based on the data retrieved, botulinum toxin has been proven to provide good short-term outcomes, especially in patients with pain sensitization, by modulating neurotransmitter release, peripheral nociceptive transduction, and acting on the control of chronic pain from central sensitization.

Combined subchondral and intra-articular injections of bone marrow aspirate concentrate provide stable results up to 24 months.

PURPOSE: The aim of this study was to evaluate the clinical and imaging findings up to 24 months of follow-up in patients treated with combined subchondral and intra-articular bone marrow aspirate concentrate (BMAC) injections for the treatment of knee osteoarthritis (OA). METHODS: Thirty consecutive patients (19 males, 11 females) aged between 40 and 75 years (mean age 56.4 ± 8.1 years) with unilateral symptomatic knee OA (Kellgren-Lawrence 2-3) were included in the study. Patients were treated with combined intra-articular and subchondral bone BMAC injections (total 9 ml) under fluoroscopic control. IKDC subjective score, VAS for pain, KOOS, and EQ-VAS were prospectively evaluated up to 24 months. Radiographs were performed at baseline and at 24 months after the procedure. MRI was evaluated with the WORMS score at baseline, 6-12 months, and 24 months of follow-up. The statistical analysis was performed using SPSS v.19.0 and for all tests p < 0.05 was considered significant. RESULTS: No major complications and a 13% failure rate were reported. The IKDC subjective score remained stable from 62.6 ± 19.4 at 12 months to 63.4 ± 17.1 at 24 months (both p < 0.0005 compared to baseline, 40.5 ± 12.5). Similar improvements were reported for all KOOS subscales, while EQ-VAS did not report any significant improvement. VAS pain worsened from 3.0 ± 1.9 at 12 months to 4.4 ± 1.8 at the final follow-up (p = 0.0001), although remaining lower compared to the baseline value of 6.3 ± 1.8 (p = 0.002). The radiographic evaluation did not reveal signs of improvement or deterioration of the OA grade. The MRI findings showed a worsening in marginal osteophytes and synovitis, but a significant reduction of bone marrow edema at 24 months (p < 0.0005). CONCLUSION: Combined intra-articular and subchondral BMAC injections provided clinical and imaging benefits up to 24 months for the treatment of symptomatic knee OA, with durable clinical results, a low failure rate, and a significant reduction of bone marrow edema.

Conservative vs. Surgical Management for Femoro-Acetabular Impingement: A Systematic Review of Clinical Evidence.

Femoro-acetabular impingement (FAI) syndrome is one of the most studied conditions in sports medicine. Surgical or conservative approaches can be proposed for treating FAI, although the best standard of care is not established yet. Our aim is to provide a comprehensive review of the best treatment for FAI syndrome evaluating differences in outcomes between surgical and non-operative management. A literature search was carried out on the PubMed, EMBASE, Scopus, and PEDro databases, using the following keywords: "femoroacetabular impingement", "FAI", in association with "surgery", "arthroscopy", "surgical" and "conservative", "physiotherapy", "physical therapy", "rehabilitation", "exercise". Only Level I RCTs were included. Four articles were selected for this systematic review. Our analysis showed different therapeutic protocols, follow-up periods, and outcomes; however, three out of the four studies included favored surgery. Our study demonstrates beneficial effects for both arthroscopic treatment and a proper regimen of physical therapy, nevertheless a surgical approach seemed to offer superior short-term results when compared to conservative care only. Further trials with larger sample sizes and longer follow-ups are needed to assess the definitive approach to the FAI condition.

Navigating around the Current Options to Preserve and Regenerate Meniscus: A Long Journey Still to Be Pursued.

The beginning of meniscal surgery was attributed to Annadale at the end of the 19th century: interestingly, he performed the first documented surgical repair of the meniscus [...].

In Vivo Model of Osteoarthritis to Compare Allogenic Amniotic Epithelial Stem Cells and Autologous Adipose Derived Cells.

The challenge of osteoarthritis (OA) is to find a minimally invasive orthobiological therapy to contrast OA progression, on inflammatory and structural fronts. The aim of the present study is to compare the effects of an intra-articular injection of three orthobiological treatments, autologous culture expanded adipose-derived mesenchymal stromal cells (ADSCs), autologous stromal vascular fraction (SVF) and allogenic culture expanded amniotic epithelial stem cells (AECs), in an animal model of OA. OA was induced in 24 sheep by bilateral lateral meniscectomy and, at 3 and 6 months post-treatment, the results were analyzed with macroscopy, histology, histomorphometry, and biochemistry. All the three treatments showed better results than control (injection of NaCl), but SVF and AECs showed superiority over ADSCs, because they induced higher cartilage regeneration and lower inflammation. SVF showed better results than AECs at 3 and 6 months. To conclude, SVF seems to be more favorable than the other biological options, because it is easily obtained and rapidly used after harvesting, with good healing potential. AECs cause no discomfort and could be also considered for the treatment of OA joints.

Gender-Related Aspects in Osteoarthritis Development and Progression: A Review.

Osteoarthritis (OA) is a common degenerative joint disease treated mostly symptomatically before approaching its definitive treatment, joint arthroplasty. The rapidly growing prevalence of OA highlights the urgent need for a more efficient treatment strategy and boosts research into the mechanisms of OA incidence and progression. As a multifactorial disease, many aspects have been investigated as contributors to OA onset and progression. Differences in gender appear to play a role in the natural history of the disease, since female sex is known to increase the susceptibility to its development. The aim of the present review is to investigate the cues associated with gender by analyzing various hormonal, anatomical, molecular, and biomechanical parameters, as well as their differences between sexes. Our findings reveal the possible implications of gender in OA onset and progression and provide evidence for gaps in the current state of art, thus suggesting future research directions.