The Ultimate Guide to Understanding and Managing Osteoarthritis Effectively

Pain relief for osteoarthritis. welling, and stiffness. Imagine the hinges of a door rusting and eroding, making the door creaky and harder to move. Similarly, when the smooth, protective covering of our joints wears down, moving becomes difficult and painful. It’s widely recognized not only for its ubiquitous nature but also for the impact it casts on the day-to-day life of individuals, warranting a thorough understanding and streamlined management approaches.

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Pain relief for osteoarthritis: How Common is Osteoarthritis?

Exploring the numerical and demographic landscape, “Osteoarthritis affects millions” of people around the world, having its presence notably among adults aged 60 and above. Dipping into the data, around 10% of men and 18% of women in this age group are confronted with OA. But it doesn’t play favorites! While the older age group is more susceptible, younger people can also be affected, especially when factors like genetics, weight, and joint injuries come into the picture. It’s crucial to note that while OA might predominantly impact some joints like knees, hips, and hands, it doesn’t restrict itself and can affect any joint, curating a diverse panorama of challenges and management tactics. How Movement Patterns Influence Osteoarthritis

Why Should We Pay Attention: The Importance of Understanding OA in Medical Practice

Taking a broader perspective, **understanding and managing OA** is not just paramount for healthcare providers but for everyone. Why? Because it’s not only a tale of worn-out joints but a narrative that intertwines with various aspects of an individual’s life, including their mobility, daily activities, and even mental health. From a medical standpoint, it’s like solving a puzzle – healthcare professionals strive to manage pain, improve joint function, and ensure a good quality of life for those affected. For patients and caregivers, knowledge about OA equips them with the empowerment to engage in active management, from adhering to medications to adopting lifestyle changes, rendering OA not merely as a condition but a realm that warrants collective understanding, awareness, and action.

Moving Forward: Sections to Explore in Your OA Journey

Navigating through the following sections, readers of all backgrounds will discover further insights into OA, including its intricate workings, how it’s diagnosed, strategies to manage it, and how real-life scenarios unfold.

Pathophysiology

Normal Joint Anatomy and Physiology

Joints are astoundingly engineered biological structures, meticulously designed to facilitate motion and bear loads. A typical synovial joint, like the knee or hip, is comprised of two bone surfaces coated in a layer of smooth, friction-reducing articular cartilage. These structures are enveloped by the joint capsule, lined with synovial membrane, producing synovial fluid – a lubricant that nourishes and minimizes friction within the cartilage. Ligaments and tendons provide stability and facilitate movement, ensuring synchronized, pain-free motion.

Pathological Changes in OA

Cartilage Degradation

The hallmark of OA, cartilage degradation, refers to the gradual erosion of the articular cartilage, initiating a cascade of pathological events. Chondrocytes, the primary cells in cartilage, undergo metabolic and phenotypic changes, contributing to a breakdown of the extracellular matrix (ECM) – composed chiefly of collagen and proteoglycans. The degradation metabolites and matrix fragments are postulated to act as bioactive molecules, instigating further cartilage catabolism and igniting inflammatory cascades.

Bone Remodeling

Following cartilage erosion, the subchondral bone is exposed and subjected to abnormal mechanical stresses. In response, it undergoes remodeling, with areas of sclerosis and the formation of cysts. This process is regulated by an interplay of osteoblasts and osteoclasts, influenced by mediators like RANKL and OPG, signifying an intricate balance between bone formation and resorption.

Synovial Inflammation

Contrary to classical beliefs, OA is not solely a non-inflammatory arthropathy. Synovitis is frequently observed, even in early-stage OA. Pro-inflammatory mediators like cytokines (IL-1β, TNF-α) and adipokines from infrapatellar fat pads perpetuate synovial inflammation and influence the progression of OA by exacerbating cartilage degradation and instigating pain pathways.

Osteophyte Formation

Osteophytes, or bone spurs, arise at the joint margins. While traditionally viewed as a pathological signature, their formation is also hypothesized as a compensatory response to augment joint surface area and dissipate loads. However, osteophytes contribute to joint pain and may limit range of motion, possessing clinical significance.

Molecular and Cellular Mechanisms

At a molecular level, OA showcases a disarray in the anabolic and catabolic activities within the joint. Metalloproteinases (MMPs) and aggrecanases, chiefly ADAMTS-4 and ADAMTS-5, orchestrate ECM degradation, while anti-catabolic factors like TIMPs are downregulated. Cellularly, chondrocytes exhibit aberrant behaviors, such as the formation of chondrocyte clusters and the secretion of pro-inflammatory and catabolic mediators, substantiating an environment conducive for joint degeneration.

Risk Factors

Genetic Predispositions

Genetic factors significantly modulate OA susceptibility. Polymorphisms in genes regulating cartilage matrix components (e.g., COL9A1, AGC1) and those influencing bone density and structure are implicated in OA pathogenesis, presenting a layer of complexity in its onset and progression.

Age and Gender

Age surfaces as a robust risk factor for OA, attributed to cumulative wear and tear, diminished cellular reparative capacity, and altered biomechanical properties. Gender is also pivotal, with females exhibiting heightened prevalence and severity, potentially modulated by hormonal and biomechanical distinctions.

Obesity

Obesity propels OA via mechanical and metabolic pathways. Augmented joint loading and altered biomechanics are coupled with metabolic inflammation, wherein adipokines and fatty acids serve as mediators linking obesity to cartilage degradation.

Joint Injury and Overuse

A history of joint injury, malalignment, or chronic overuse substantially escalates OA risk, underscoring the potent influence of biomechanical factors in its pathogenesis.

For medical professionals, appreciating the detailed pathophysiology of OA encompasses not only understanding the disease cascade but also engaging in a multi-modal management strategy. Future sections may dive deeper into diagnostic nuances, management paradigms, and innovative therapeutic avenues, creating a scaffold for efficacious patient management and research undertakings.

Clinical Presentation and Diagnosis

Symptomatology

Pain

Pain in OA is multifaceted, emanating not only from intra-articular structures like the synovium and periosteum but also from the surrounding musculature, tendons, and ligaments. This pain, often described as a deep, aching sensation, tends to amplify with joint use and diminish with rest. The comprehension of nociceptive pathways, neurogenic mediators, and the roles of peripheral and central sensitization in OA pain are pivotal for targeted management strategies.

Stiffness

Joint stiffness, particularly morning stiffness which typically wanes within 30 minutes of waking and also recurs after periods of inactivity, is another hallmark. It’s critical to elucidate the duration of stiffness and differentiate it from the prolonged stiffness observed in inflammatory arthritides to guide appropriate investigations and management.

Loss of Motion

The degradation and remodeling processes limit the joint’s range of motion (ROM). A comprehensive assessment should evaluate both passive and active ROM, discerning the contributions of pain, effusion, and structural aberrations like osteophytes to movement limitation.

Crepitus and Other Physical Findings

Crepitus, the audible or palpable friction in a joint during movement, is a common clinical feature. While not pathognomonic, it provides insight into the structural integrity of the joint. Bony enlargements, joint line tenderness, and effusion should also be meticulously assessed.

Diagnostic Criteria

The American College of Rheumatology (ACR) criteria have traditionally been employed, combining clinical and radiographic parameters to establish an OA diagnosis. Although beneficial in a research context, in clinical practice, an amalgamation of history, physical examination, and imaging often shapes the diagnostic process. The discernment of typical symptomatology (like activity-related pain and brief morning stiffness) and congruent physical and radiographic findings are quintessential.

Imaging Techniques

The Ultimate Guide to Understanding and Managing Osteoarthritis Effectively

X-rays

Conventional radiography remains pivotal for OA diagnosis, providing visualizations of characteristic features like joint space narrowing (due to cartilage loss), osteophyte formation, subchondral sclerosis, and cysts. However, it’s worth noting the occasional discordance between radiographic findings and clinical symptomatology.

MRI

MRI, while not typically utilized in standard OA diagnostic protocols due to its cost and accessibility, can be invaluable when assessing soft tissue structures like the meniscus and ligaments and in visualizing early cartilage abnormalities. MRI provides a more detailed view of the joint and can detect early OA changes in cartilage, bone, and soft tissues, even before they become apparent on X-rays (1).

Differential Diagnosis

Navigating the differential diagnosis for OA mandates a systematic approach, given the plethora of conditions that can mirror its presentation. Rheumatoid arthritis, psoriatic arthritis, and other inflammatory arthritides should be considered, necessitating evaluation of inflammatory markers and autoantibodies where appropriate. Additionally, metabolic conditions like gout or pseudogout and infectious arthritides also warrant consideration. Mechanically induced conditions, such as meniscal tears or ligamentous injuries, should also be contemplated, especially in individuals presenting with acute symptoms or following trauma.

Grasping the diverse and sometimes subtle aspects of OA’s clinical presentation and diagnostic journey is essential for healthcare providers. Understanding symptom nuances, employing apt diagnostic criteria, utilizing imaging judiciously, and navigating through the differential diagnosis with a systematic, evidence-based approach is vital to managing this prevalent and impactful condition effectively and efficiently within the clinical setting. Further sections could potentially explore therapeutic options, spanning pharmacological, non-pharmacological, and surgical interventions, and delve into prognostic aspects, thereby providing a holistic, clinically-oriented guide for healthcare professionals navigating OA in their practice.

Management Strategies

Navigating through the multifaceted domain of managing Osteoarthritis (OA) requires a strategic and patient-centric approach. Given the symptomatic and structural complexity of OA, amalgamating non-pharmacological, pharmacological, and surgical interventions is pivotal to offering holistic care. Let’s delve into each strategy with nuanced insights for healthcare professionals.

Non-Pharmacological Interventions

Physical Therapy

Leveraging physical therapy optimizes functional mobility and mitigates disability. Interventions often comprise strength training, flexibility exercises, and aerobic conditioning, tailored to individual capacities and limitations. Furthermore, therapies like hydrotherapy can utilize buoyancy to facilitate movement with minimized joint stress, propelling optimal engagement in exercises.

Physical therapy, often a first-line treatment for OA, emphasizes pain management, and improvement of joint function through exercises, and joint mobilization techniques (2).

Structural Diagnosis & Management

The fascinating world of physiotherapy brings us a super special technique known as Structural Diagnosis and Management (SDM), which is like a magical tool kit filled with various helpful strategies to make our bodies feel better and move more freely! Imagine if your body was a big, complex puzzle; SDM uses cool tricks like manipulation (gentle moving and adjusting), muscle activation (helping muscles wake up and work right), stretching (lengthening our muscles to keep them happy), muscle press-pull (a technique to move and massage muscles), strengthening (making muscles stronger with specific exercises), and joint mobilization (helping our joints move smoothly) to solve that puzzle, especially when we’re feeling pain or having trouble moving around. And guess what? Agrani Specialized Manipulation Therapy Centre is like a wonderland for this amazing technique! They have expert therapists who are like body detectives, using SDM to figure out exactly what your body needs to feel its best. Choosing Agrani means choosing a place that’s not just super good at what they do, but also super caring about making your journey to feeling better as smooth and comfy as possible. So, it’s like choosing a special team that helps your body speak, understand, and solve its own mysterious language!

Occupational Therapy

Occupational therapy focuses on helping individuals perform daily activities (e.g., dressing, cooking) with ease, suggesting adaptive techniques, and devices to reduce joint stress and manage pain (3). Professionals should work synergistically with patients, identifying pain triggers and functional impediments in day-to-day tasks, thereby crafting individualized adaptive strategies.

Weight Management

Addressing adiposity is crucial given the biomechanical and systemic inflammatory implications of excessive body weight on OA progression. Weight management is crucial, especially in knee OA, as a 5-10% weight loss can significantly reduce pain and improve function (4). Crafting and navigating through personalized, realistic, and medically sound weight management strategies, involving dietary modifications and appropriate physical activities, should be underscored in the management plan.

Assistive Devices

Implementing assistive devices, from braces to walking aids, should be tailored to the individual’s anatomical and functional status. Insight into the optimal use and potential limitations of devices like unloader knee braces or specialized footwear is pivotal to ensuring their efficacy and adherence.

Pharmacological Management

Analgesics

Acetaminophen and topical nonsteroidal anti-inflammatory drugs (NSAIDs) often form the first line in pain management (5). Navigating through the pharmacodynamics, potential side effects (such as hepatic impact of acetaminophen), and patient comorbidities is pivotal in ensuring safe and effective analgesia.

Anti-Inflammatory Agents

Nonsteroidal anti-inflammatory drugs (NSAIDs) play a pivotal role in managing OA by addressing both pain and inflammation, but their long-term use poses risks, especially gastrointestinal and cardiovascular (6). Employing the lowest effective dose and considering gastroprotective agents for at-risk populations form part of prudent prescribing.

Disease-Modifying Drugs

The exploration of disease-modifying osteoarthritis drugs (DMOADs) is ongoing, necessitating healthcare professionals to stay abreast with emerging research. While several agents are under investigation, their place in routine clinical practice awaits robust evidence and regulatory approval.

Surgical Interventions

Joint Replacement

The Ultimate Guide to Understanding and Managing Osteoarthritis Effectively

Total joint arthroplasty remains a gold-standard intervention for end-stage OA, providing substantial improvements in pain and function. Understanding the indications, pre-operative optimizations, post-operative rehabilitative strategies, and potential complications is integral to holistic management.

Osteotomies

The Ultimate Guide to Understanding and Managing Osteoarthritis Effectively

For select populations, particularly younger patients with unilateral disease, high tibial osteotomies might provide symptomatic relief and potentially delay the need for joint replacement. Comprehensive insights into selection criteria, surgical techniques, and recovery pathways are essential.

Arthroscopy

The Ultimate Guide to Understanding and Managing Osteoarthritis Effectively

Although arthroscopy and related procedures, like arthroscopic debridement, have been utilized in OA management, recent evidence highlighting their limited efficacy in many OA contexts necessitates judicious application and thorough patient counseling (7).

In comprehensively managing OA, healthcare professionals ought to navigate through a spectrum of strategies with a profound understanding of their mechanistic actions, indications, and limitations. Adopting an integrative, evidence-based, and patient-centric approach ensures the amplification of quality of life and functional outcomes for individuals navigating through the complexities of Osteoarthritis.

Advances and Challenges in OA Research and Treatment

A deeper exploration into the realms of Osteoarthritis (OA) research and treatment unfolds an intricate tapestry of potential advancements juxtaposed with persistent challenges. This dichotomy propels a rigorous pursuit of knowledge, advancing our understanding of pathogenesis and enhancing therapeutic prospects, yet is mitigated by inherent complexities and hurdles in the field.

Emerging Therapies

Cell Therapy

In the realm of cell therapy, Mesenchymal Stem Cells (MSCs) have garnered attention for their potential in regenerating damaged articular cartilage and modulating local inflammatory responses (8). While early studies indicate promise, extensive research is warranted to decipher optimal cell sources, delivery methods, and defining contexts wherein therapeutic efficacy is maximized.

Gene Therapy

Gene therapy seeks to rectify or modulate genetic expressions involved in OA pathogenesis, offering prospects of targeted, local, and sustained therapeutic delivery. Navigating through viral vectors, regulating gene expressions, and ensuring precise targeting demands meticulous exploration to circumvent potential off-target effects and immunogenic responses.

Biologic Agents

Biologic agents like Platelet-Rich Plasma (PRP) have generated attention due to their potential anti-inflammatory and regenerative properties. Some studies have suggested that PRP might be beneficial in reducing pain and improving joint function in knee OA, yet there exists a dearth of large-scale randomized controlled trials, and guidelines generally remain conservative in recommending their use due to limited evidence and varied study results (9).

Multidisciplinary Approach to OA Management

Harmonizing care through a multidisciplinary lens substantiates a nuanced, comprehensive, and patient-centered approach to managing Osteoarthritis (OA). This modality not only intertwines the expertise of varied healthcare professionals but also ensconces patient education and empowerment as pivotal facets of management.

Role of Primary Care Physicians

Primary Care Physicians (PCPs) stand as pivotal pillars, often being the first point of contact for individuals experiencing OA symptoms. Their role extends from initial assessment, crafting management plans, and coordinating referrals, to chronic disease management and facilitating multidisciplinary care. Moreover, PCPs are intrinsic in managing comorbidities and ensuring a holistic approach that embraces both the musculoskeletal and systemic implications of OA.

Specialists Involvement

Rheumatologists

The expertise of rheumatologists proves indispensable, particularly in cases involving diagnostic dilemmas, complexities, or systemic manifestations. They facilitate in-depth evaluations, guide toward optimal pharmacological management, and are instrumental in managing inflammatory and metabolic components of OA.

Orthopedic Surgeons

Orthopedic surgeons play a cardinal role, especially in advanced-stage OA where surgical interventions, such as joint replacements or osteotomies, become viable. Their insights into biomechanical implications, surgical options, and postoperative management sculpt pivotal pathways in managing structural aspects of OA.

Physical Therapists

Physical therapists play a cardinal role in providing non-pharmacological management for OA, including exercise prescription and lifestyle modification advice, which are crucial for managing and even slowing the progression of OA (10). They craft individualized exercise regimens, guide through adaptive strategies, and are pivotal in post-surgical rehabilitation, ensuring optimal functional recovery and minimizing disability.

Coordinating Comprehensive Care

Effective coordination between primary care physicians, specialists, and other healthcare professionals is vital for ensuring comprehensive care. A well-coordinated approach can facilitate more personalized care strategies, monitoring disease progression, and adapting management plans accordingly (11).

Patient Education and Self-Management Strategies

Educating patients and caregivers empowers them to actively participate in management. This involves elucidating the disease process, therapeutic options, and self-management strategies encompassing exercise, weight management, and joint protection. Utilizing educational materials, workshops, and digital platforms enhances reach and understanding.

Moreover, embedding self-management strategies, such as pain management techniques, adaptive devices, and lifestyle modifications, empowers patients to navigate through daily challenges effectively. Ensuring these strategies are realistic, adaptable, and aligned with individual capacities and challenges fortifies their practicality and sustainability.

Embarking on OA management through a multidisciplinary approach not only amalgamates varied expertise but also ensures that care is holistically tuned to the multifaceted needs and challenges encountered by individuals with OA. While each professional brings a unique lens of expertise, it is the harmonic integration of these perspectives, amalgamated with patient education and empowerment, that crafts a robust, comprehensive, and compassionate framework for managing Osteoarthritis in a nuanced and effective manner.

Conclusion

Osteoarthritis (OA), a joint condition that predominantly affects the knees, hips, and hands, is synonymous with pain, stiffness, and oftentimes, reduced mobility, impacting countless lives across the globe. As we punctuate our guide on understanding and managing this prevalent condition, let’s distill the pivotal takeaways and gaze toward the unfolding tapestry of OA’s future research and management.

As we peer into the future, the horizon of OA research and management is ablaze with potential advancements and challenges that promise to reshape our understanding and therapeutic approaches. The realms of cell therapy, gene therapy, and biologic agents pose as enticing frontiers, potentially offering novel modalities to alter disease progression and enhance symptom management. Yet, these pathways are also entwined with intricate challenges, from validating efficacy and safety to navigating through ethical and accessibility considerations.

The continuously evolving landscape of OA necessitates an unyielding commitment to continued learning and adaptability amongst healthcare professionals and the general populace alike. For individuals navigating through the daily realities of OA and for those engaged in providing care, remaining abreast with emerging research findings, novel therapeutic modalities, and evolving guidelines is imperative. Furthermore, fostering an environment that encourages shared decision-making, patient education, and empowerment stands paramount in enhancing care quality and outcomes.

In synthesizing, OA is more than a medical condition; it is intertwined with individual stories, experiences, and challenges. While scientific advancements propel our capabilities forward, it is the amalgamation of robust science, compassionate care, patient empowerment, and a multidisciplinary ethos that will truly sculpt a future where OA management is not only effective but also personable, accessible, and nuanced to the multifaceted needs of those affected.

FAQ’s

1. Q: What is Osteoarthritis (OA) and how common is it?

A: Osteoarthritis (OA) is a degenerative joint disorder characterized by the breakdown of joint cartilage and underlying bone. It is one of the most common chronic joint conditions, affecting approximately 32.5 million adults in the United States according to the Centers for Disease Control and Prevention (CDC).

2. Q: What are the primary symptoms of Osteoarthritis?

A: The primary symptoms include joint pain, stiffness, swelling, and reduced range of motion. Over time, the condition can also lead to joint instability and deformities.

3. Q: How is Osteoarthritis diagnosed?

A: OA is typically diagnosed through a combination of clinical evaluation, including a physical examination and medical history, and imaging tests such as X-rays or Magnetic Resonance Imaging (MRI) to assess joint damage and rule out other conditions.

4. Q: What are the risk factors associated with developing Osteoarthritis?

A: Key risk factors include aging, genetics, joint injuries, obesity, gender (it’s more common in women), occupational hazards that put stress on joints, and sports that involve repetitive joint use or high impact.

5. Q: Can Osteoarthritis be cured?

A: Currently, there is no cure for OA, but a range of treatments is available to manage symptoms and improve joint function, including pharmacological, non-pharmacological, and surgical interventions.

6. Q: How can I manage Osteoarthritis pain without using medications?

A: Non-pharmacological interventions like physical therapy, occupational therapy, weight management, and using assistive devices are often recommended to manage OA pain and maintain joint function.

7. Q: Are there any surgical options available for treating Osteoarthritis?

A: Yes, surgical options such as joint replacement, osteotomies, and arthroscopy can be considered, especially when conservative management is insufficient in controlling symptoms and enhancing life quality.

8. Q: How does physical therapy aid in managing Osteoarthritis?

A: Physical therapy can provide exercises tailored to enhance joint flexibility, strengthen surrounding muscles, and potentially alleviate the stress on the joints, thereby managing pain and improving function.

9. Q: Can diet and nutrition impact Osteoarthritis management?

A: Yes, maintaining a balanced diet and healthy weight is crucial in managing OA as obesity can exacerbate the stress on weight-bearing joints, enhancing pain and progression of the disease.

10. Q: What ongoing research is there concerning Osteoarthritis treatments and management?

A: Ongoing research into OA spans numerous areas, including the development of disease-modifying drugs, exploring various biologic agents, and innovating in cell and gene therapy to potentially alter the disease progression.

References

1. Hunter, D.J., Zhang, W., Conaghan, P.G., Hirko, K., Menashe, L., Reichmann, W.M. and Losina, E., 2011. Responsiveness and reliability of MRI in knee osteoarthritis: a meta-analysis of published evidence. Osteoarthritis and cartilage, 19(5), pp.589-605. https://www.sciencedirect.com/science/article/pii/S1063458411000720

2. Bennell, K.L. and Hinman, R.S., 2011. A review of the clinical evidence for exercise in osteoarthritis of the hip and knee. Journal of science and medicine in sport, 14(1), pp.4-9 https://www.sciencedirect.com/science/article/pii/S1440244010001647

3. Steultjens, M.P.M., Dekker, J.V., Van Baar, M.E., Oostendorp, R.A.B. and Bijlsma, J.W.J., 2000. Range of joint motion and disability in patients with osteoarthritis of the knee or hip. Rheumatology, 39(9), pp.955-961. https://academic.oup.com/rheumatology/article-abstract/39/9/955/1784028

4. Christensen, R., Bartels, E.M., Astrup, A. and Bliddal, H., 2007. Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis. Annals of the rheumatic diseases, 66(4), pp.433-439. https://ard.bmj.com/content/66/4/433.short

5. Hochberg, M.C., Altman, R.D., April, K.T., Benkhalti, M., Guyatt, G., McGowan, J., Towheed, T., Welch, V., Wells, G. and Tugwell, P., 2012. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis care & research, 64(4), pp.465-474. https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.21596

6. McAlindon, T.E., Bannuru, R., Sullivan, M.C., Arden, N.K., Berenbaum, F., Bierma-Zeinstra, S.M., Hawker, G.A., Henrotin, Y., Hunter, D.J., Kawaguchi, H. and Kwoh, K., 2014. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis and cartilage, 22(3), pp.363-388. https://www.sciencedirect.com/science/article/pii/S1063458414000168

7. Kirkley, A., Birmingham, T.B., Litchfield, R.B., Giffin, J.R., Willits, K.R., Wong, C.J., Feagan, B.G., Donner, A., Griffin, S.H., D’Ascanio, L.M. and Pope, J.E., 2008. A randomized trial of arthroscopic surgery for osteoarthritis of the knee. New England Journal of Medicine, 359(11), pp.1097-1107. https://www.nejm.org/doi/full/10.1056/nejmoa0708333

8. Pers, Y.M., Rackwitz, L., Ferreira, R., Pullig, O., Delfour, C., Barry, F., Sensebe, L., Casteilla, L., Fleury, S., Bourin, P. and Noël, D., 2016. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem cells translational medicine, 5(7), pp.847-856. https://academic.oup.com/stcltm/article-abstract/5/7/847/6397809

9. Laudy, A.B., Bakker, E.W., Rekers, M. and Moen, M.H., 2015. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. British journal of sports medicine, 49(10), pp.657-672. https://bjsm.bmj.com/content/49/10/657.short

10. Uthman, O.A., Van Der Windt, D.A., Jordan, J.L., Dziedzic, K.S., Healey, E.L., Peat, G.M. and Foster, N.E., 2013. Exercise for lower limb osteoarthritis: systematic review incorporating trial sequential analysis and network meta-analysis. Bmj, 347. https://www.bmj.com/content/347/bmj.f5555

11. Hunter, D.J., Schofield, D. and Callander, E., 2014. The individual and socioeconomic impact of osteoarthritis. Nature Reviews Rheumatology, 10(7), pp.437-441. https://www.nature.com/articles/nrrheum.2014.44

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