Emerging and New Treatment Options for Knee Osteoarthritis

: Osteoarthritis (OA) is the most prevalent type of arthritis worldwide, resulting in pain and often chronic disability and a significant burden on healthcare systems globally. Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee OA has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, no single treatment has regenerating potential for damaged articular cartilage. Due to a better understanding of osteoarthritis, innovative new treatment options have been developed. In this narrative review, we focus on emerging OA knee treatments, relieving symptoms, and regenerating damaged articular cartilage that includes intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC), exosomes, interleukin-1 blockers, gene-based therapy, and bisphosphonate.

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Cellular transplantation and platelet-rich plasma injections for discogenic pain: a contemporary review

Regenerative Medicine ◽

10.2217/rme-2020-0146 ◽

2021 ◽

Author(s):

Brian Fiani ◽

Alden Dahan ◽

Mohamed H El-Farra ◽

Michael W Kortz ◽

Juliana M Runnels ◽

...

Keyword(s):

Animal Studies ◽

Chronic Back Pain ◽

Platelet Rich Plasma ◽

Treatment Options ◽

Intervertebral Discs ◽

Disc Disease ◽

Discogenic Pain ◽

Cellular Transplantation ◽

New Treatment ◽

Growth Factor Therapy

Degenerative disc disease (DDD) is the leading cause of chronic back pain. It is a pathologic condition associated with aging and is believed to result from catabolic excess in the intervertebral discs’ (IVD) extracellular matrix. Two new treatment options are intradiscal cellular transplantation and growth factor therapy. Recent investigations on the use of these therapies are discussed and compared with emerging evidence supporting novel cellular injections. At present, human and animal studies provide a compelling rationale for the use of cellular injections in the treatment of discogenic pain. Since DDD results from the IVD extracellular matrix’s unmitigated catabolism, cellular injections are used to induce regeneration and homeostasis in the IVD. Here, we review intervertebral disc anatomy, DDD pathophysiology and clinical considerations, as well as the current and emerging literature investigating outcomes associated with cellular transplantation and platelet-rich plasma for discogenic pain. Further high-quality trials are certainly warranted.

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Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations

Genes ◽

10.3390/genes11080854 ◽

2020 ◽

Vol 11 (8) ◽

pp. 854

Author(s):

Dragan Primorac ◽

Vilim Molnar ◽

Eduard Rod ◽

Željko Jeleč ◽

Fabijan Čukelj ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Platelet Rich Plasma ◽

Treatment Options ◽

Stromal Vascular Fraction ◽

Disease Stage ◽

Knee Oa ◽

Marrow Mesenchymal Stem Cells ◽

The Moment ◽

And Function ◽

Orthopedic Patients

Being the most common musculoskeletal progressive condition, osteoarthritis is an interesting target for research. It is estimated that the prevalence of knee osteoarthritis (OA) among adults 60 years of age or older is approximately 10% in men and 13% in women, making knee OA one of the leading causes of disability in elderly population. Today, we know that osteoarthritis is not a disease characterized by loss of cartilage due to mechanical loading only, but a condition that affects all of the tissues in the joint, causing detectable changes in tissue architecture, its metabolism and function. All of these changes are mediated by a complex and not yet fully researched interplay of proinflammatory and anti-inflammatory cytokines, chemokines, growth factors and adipokines, all of which can be measured in the serum, synovium and histological samples, potentially serving as biomarkers of disease stage and progression. Another key aspect of disease progression is the epigenome that regulates all the genetic expression through DNA methylation, histone modifications, and mRNA interference. A lot of work has been put into developing non-surgical treatment options to slow down the natural course of osteoarthritis to postpone, or maybe even replace extensive surgeries such as total knee arthroplasty. At the moment, biological treatments such as platelet-rich plasma, bone marrow mesenchymal stem cells and autologous microfragmented adipose tissue containing stromal vascular fraction are ordinarily used. Furthermore, the latter two mentioned cell-based treatment options seem to be the only methods so far that increase the quality of cartilage in osteoarthritis patients. Yet, in the future, gene therapy could potentially become an option for orthopedic patients. In the following review, we summarized all of the latest and most important research in basic sciences, pathogenesis, and non-operative treatment.

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Injections in the osteoarthritic knee: a review of current treatment options

EFORT Open Reviews ◽

10.1302/2058-5241.6.210026 ◽

2021 ◽

Vol 6 (6) ◽

pp. 501-509

Author(s):

Gerardo Fusco ◽

Francesco M. Gambaro ◽

Berardo Di Matteo ◽

Elizaveta Kon

Keyword(s):

Platelet Rich Plasma ◽

Symptomatic Relief ◽

Treatment Options ◽

Cartilage Degradation ◽

Current Treatment ◽

Biologic Agents ◽

Knee Oa ◽

Molecular Approaches

Knee osteoarthritis is a degenerative condition characterized by progressive cartilage degradation, subchondral damage, and bone remodelling. Among the approaches implemented to achieve symptomatic and functional improvements, injection treatments have gained increasing attention due to the possibility of intra-articular delivery with reduced side effects compared to systemic therapies. In addition to well-established treatment options such as hyaluronic acid (HA), cortico-steroids (CS) and oxygen-ozone therapy, many other promising products have been employed in the last decades such as polydeoxyribonucleotide (PDRN) and biologic agents such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Moreover, ultrasound-guided intra-meniscal injection and X-ray-guided subchondral injection techniques have been introduced into clinical practice. Even when not supported by high evidence consensus, intra-articular CS and HA injections have gained precise indications for symptomatic relief and clinical improvement in OA. Biological products are strongly supported by in vitro evidence but there is still a lack of robust clinical evidence. PRP and MSCs seem to relieve OA symptoms through a regulation of the joint homeostasis, even if their capability to restore articular cartilage is still to be proved in vivo. Due to increasing interest in the subchondral bone pathology, subchondral injections have been developed with promising results in delaying joint replacement. Nevertheless, due to their recent development and the heterogeneity of the injected products (biologic agents or calcium phosphate), this approach still lacks strong enough evidence to be fully endorsed. Combined biological treatments, nano-molecular approaches, monoclonal antibodies and ‘personalized’ target therapies are currently under development or under investigation with the aim of expanding our armamentarium against knee OA. Cite this article: EFORT Open Rev 2021;6:501-509. DOI: 10.1302/2058-5241.6.210026

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New treatment options for lipid-lowering therapy in subjects with type 2 diabetes

Acta Diabetologica ◽

10.1007/s00592-017-1089-4 ◽

2017 ◽

Vol 55 (3) ◽

pp. 209-218 ◽

Cited By ~ 18

Author(s):

Roberto Scicali ◽

Antonino Di Pino ◽

Viviana Ferrara ◽

Francesca Urbano ◽

Salvatore Piro ◽

...

Keyword(s):

Type 2 Diabetes ◽

Treatment Options ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Lowering Therapy ◽

New Treatment

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Developments in Smart Multi-Function Gait Assistive Devices for the Prevention and Treatment of Knee Osteoarthritis—A Literature Review

Applied Sciences ◽

10.3390/app112210947 ◽

2021 ◽

Vol 11 (22) ◽

pp. 10947

Author(s):

Hanatsu Nagano ◽

William Sparrow ◽

Rezaul Begg

Keyword(s):

Articular Cartilage ◽

Knee Joint ◽

Knee Osteoarthritis ◽

Treatment Options ◽

Smart Systems ◽

Messenger Ribonucleic Acid ◽

Knee Oa ◽

Senior Population ◽

Electro Magnetic ◽

Joint Motions

Knee osteoarthritis (OA) is a degenerative condition that critically affects locomotor ability and quality of life and, the condition is particularly prevalent in the senior population. The current review presents a gait biomechanics conceptual framework for designing active knee orthoses to prevent and remediate knee OA. Constant excessive loading diminishes knee joint articular cartilage and, therefore, measures to reduce kinetic stresses due to the fact of adduction moments and joint compression are an essential target for OA prevention. A powered orthosis enables torque generation to support knee joint motions and machine-learning-driven “smart systems” can optimise the magnitude and timing of joint actuator forces. Although further research is required, recent findings raise the possibility of exoskeleton-supported, non-surgical OA interventions, increasing the treatment options for this prevalent, painful and seriously debilitating disease. Combined with advances in regenerative medicine, such as stem cell implantation and manipulation of messenger ribonucleic acid (m-RNA) transcription, active knee orthoses can be designed to incorporate electro-magnetic stimulators to promote articular cartilage resynthesis.

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Two or four injections of leukocyte-poor platelet-rich plasma for osteoarthritic knee did not affect changes of synovial cytokines and growth factors but similarly improved clinical outcomes

10.21203/rs.3.rs-745615/v1 ◽

2021 ◽

Author(s):

Srihatach Ngarmukos ◽

Chotetawan Tanavalee ◽

Chavarin Amarase ◽

Suphattra Phakham ◽

Warayapa Mingsiritham ◽

...

Keyword(s):

Growth Factors ◽

Synovial Fluid ◽

Clinical Outcomes ◽

Inflammatory Cytokines ◽

Platelet Rich Plasma ◽

Knee Oa ◽

Group A ◽

Baseline Levels ◽

One Year ◽

Group B

Abstract We compared two and four intra-articular injections of platelet-rich plasma (PRP) in terms of changes of synovial cytokines and clinical outcomes. One hundred twenty-five patients having knee OA underwent leukocyte-poor PRP with a 6-week interval. Before each PRP injection, synovial fluid aspiration was collected for investigation. Patients were divided into two or four intra-articular PRP injections (group A and B, respectively). Changes in synovial cytokines and growth factors were compared with the baseline levels of both groups, and clinical outcomes were evaluated until one year. Ninety-four patients who had completed synovial fluid collection were included for final evaluation, 51 in group A and 43 in group B. There were no differences in mean age, gender, BMI, and OA grading. The average platelet count in PRP was 430,000/µL. There were no changes of synovial inflammatory cytokines (IL-1ß, IL-6, IA-17A, and TNF-alpha), anti-inflammatory cytokines (IL-4, IL-10, IL-13, and IL-1RA), and growth factors (TGF-B1, VEGF, PDGF-AA, and PDGF-BB) between baseline levels and six weeks in group A, and 18 weeks in group B. Both groups had significantly improved clinical outcomes from six weeks including visual analog scale (VAS), patient-reported outcome measure (PROM; WOMAC and SF-12), with a significant delayed improvement of performance-based measure [PBM; time up and go (TUG), 5-time sit to stand test (5×SST), and 3-minute walk test (3-min WT)]. In conclusion, two- or four-PRP injection at a 6-week interval for knee OA demonstrated no changes of synovial cytokines and growth factors but similarly improved clinical outcomes from 6 weeks until one year.

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Characterisation of the inflammatory cytokine and growth factor profile in a rabbit model of proliferative vitreoretinopathy

Scientific Reports ◽

10.1038/s41598-019-51633-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Chee Wai Wong ◽

Ning Cheung ◽

Candice Ho ◽

Veluchamy Barathi ◽

Gert Storm ◽

...

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Inflammatory Cytokines ◽

Proliferative Vitreoretinopathy ◽

Platelet Rich Plasma ◽

Interleukin 1 ◽

Rabbit Model ◽

Gm Csf ◽

Ifn Γ ◽

Angiopoietin 2

Abstract To clarify the mechanisms and their temporal relationship in the development of proliferative vitreoretinopathy (PVR), we measured vitreous levels of pro-inflammatory cytokines and growth factors in a rabbit model of PVR. PVR was surgically induced in 11 rabbit eyes by vitrectomy, retinotomy, cryotherapy and injection of platelet-rich plasma at baseline. Severity of PVR was assessed on dilated fundal examination with indirect binocular ophthalmoscopy and graded based on the revised experimental PVR classification. Severe PVR was defined as stage 5 or worse. Vitreous concentrations of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 1 beta (IL-1 β), tumor necrosis factor beta (TNF-β), granulocyte macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-γ), C reactive protein; (CRP), placental growth factor (PlGF), platelet derived growth factor BB (PDGF-BB), vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2) at weeks 2, 3 and 4 were compared to baseline and correlations between the cytokines with PVR severity were assessed. Four weeks after PVR induction, 5 eyes (45.5%) had developed severe PVR. IL-8 was raised at 2 weeks post PVR induction (1.46 ± 0.48 pg/ml vs 0.53 ± 0.25 pg/ml, p = 0.04) and remained significantly elevated at week 4 (2.6 ± 3.1 pg/ml, p = 0.03). CRP was significantly raised at week 4 (34.8 ± 12.0 pg/ml vs 13.0 ± 13.1 pg/ml, p < 0.001). Among the growth factors, PDGF-BB was the earliest to show significantly elevated levels, at 3 weeks (50.4 ± 19.0 pg/ml vs 6.2 ± 10.1 pg/ml) and remained elevated at week 4 (p = 0.002), while PlGF (11.2 ± 7.7 pg/ml vs 5.3 ± 3.8 pg/ml, p = 0.002) and Ang2 (13617.0 ± 8170.2 pg/ml vs 38593.8 ± 8313.4, p = 0.02) were significantly raised at week 4. IFN-γ (p = 0.03), PDGF-BB (p = 0.02) and VEGF (p = 0.02) were significantly associated with PVR severity. We demonstrated that inflammatory cytokines IL-6, -8, elevation post PVR induction is followed by elevated levels of fibroproliferative growth factors, Ang2, PlGF, VEGF and PDGF-BB in the development of PVR. These findings will guide future studies targeting appropriate therapeutic strategies for the treatment of PVR.

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Conservative Treatment of Ankle Osteoarthritis

Journal of Clinical Medicine ◽

10.3390/jcm10194561 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4561

Author(s):

Sergio Tejero ◽

Estefanía Prada-Chamorro ◽

David González-Martín ◽

Antonio García-Guirao ◽

Ahmed Galhoum ◽

...

Keyword(s):

Conservative Treatment ◽

Clinical Studies ◽

Platelet Rich Plasma ◽

Scientific Evidence ◽

Treatment Options ◽

Pharmacological Treatments ◽

Ankle Osteoarthritis ◽

Knee Oa ◽

Plasma Injection ◽

Inflammatory Drugs

Despite the disabling nature of ankle osteoarthritis (OA), there is poor scientific evidence for a conservative treatment compared to the hip and knee OA. In this regard, most of the treatment options in use are not based on clinical studies of the ankle, and they are extracted from evidence obtained from clinical studies of other lower limb joints. However, this does not seem to be a good idea, since the aetiology of ankle OA is quite different from that of the hip or knee. Nonpharmacological and pharmacological treatments such as nonsteroidal anti-inflammatory drugs, hyaluronic acid, corticosteroid, platelet-rich plasma injection and mesenchymal stem cells injections have been reported. However, further research is required in this field to obtain a specific clinical practice guideline for the conservative treatment of ankle OA.

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Intra-articular Platelet-Rich Plasma Injections for Treating Knee Pain Associated with Articular Cartilage and Degenerative Meniscal Lesions

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.674 ◽

2019 ◽

Vol 7 (15) ◽

pp. 2484-2487

Author(s):

Konstantin Mitev ◽

Aleksandar Longurov

Keyword(s):

Growth Factors ◽

Articular Cartilage ◽

Platelet Rich Plasma ◽

Test Tube ◽

Biochemical Process ◽

Short Term ◽

Meniscal Lesions ◽

Meniscus Lesions ◽

Cartilage Injuries

BACKGROUND: Platelet-rich plasma (PRP) is an autologous concentration of platelets that contain a large number of growth factors. These growth factors play a role in the regeneration, repair, and acceleration of the biochemical process, thereby reducing the pain associated with injuries of the articular cartilage and meniscus AIM: The purpose of this study is to evaluate the effect of the PRP method in the treatment of knee joint cartilage injuries and degenerative meniscus lesions as well as pain relief. MATERIAL AND METHODS: The process of obtaining PRP begins by taking 15 ml of blood from the patient with a special system called Arthrex Double Syringe system. The test tube is centrifuged at 4000 rpm for 5 minutes. From the separated plasma, 5-6 ml PRP is taken and prepared for application. PRP is administered intra-articularly. RESULTS: At the Jan Mitrev Clinic in Skopje in 2018, PRP procedures were performed on 126 patients, 56 (44.4%) of whom were male, and 70 (55.6%) were female. The patients were evaluated by the Tegner Lysholm Knee Scoring Scale (TLKSS) before applying 3 doses of PRP for 7 days as well as 3 and 6 months after the application of PRP. The results showed considerable improvement 3 months after the PRP application, and 6 months after the application the results remained approximately identical. CONCLUSION: The application of PRP in the field of medicine is widely applied, and it will continue to be because the understanding of PRP therapy is increasingly refined. This therapy represents a potential and latest method in short-term pain reduction, but additional studies are needed to prove its long-term effectiveness.

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Two different regenerative injections in patients diagnosed with secondary hip osteoarthritis: A report of two cases

Journal of Experimental and Clinical Medicine ◽

10.52142/omujecm.38.2.27 ◽

2021 ◽

Vol 38 (2) ◽

pp. 204-207

Author(s):

Ferhat SAY ◽

İsmail BÜYÜKCERAN ◽

Sina COŞKUN

Keyword(s):

Growth Factors ◽

Platelet Rich Plasma ◽

Treatment Options ◽

Hip Osteoarthritis ◽

Developmental Dysplasia ◽

Effective Treatment Option ◽

Autologous Conditioned Serum ◽

Functional Scores ◽

Anti Inflammatory ◽

High Level

Non-surgical treatment options are limited in hip osteoarthritis secondary to developmental dysplasia of the hip (DDH). Treatment of Autologous Conditioned Serum (ACS) is based on the high level of anti-inflammatory cytokine production of leukocytes in peripheral blood. It is an effective treatment option which contains the cytokines and the growth factors. Platelet Rich Plasma (PRP) is a form of treatment that stimulates natural healing steps through growth factors in platelets. In this case report we aimed to present the results of ACS and PRP injection in two patients who developed secondary coxarthrosis after DDH surgery. At the 1-year follow-up examination, patient’s functional scores improved and requirement for non-steroid anti-inflammatory drugs had significantly reduced. Regenerative injections either autologous conditioned serum or platelet rich plasma treatments are safe and effective treatments and can be recommended particularly for cases of secondary hip osteoarthritis associated with DDH.

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