How to treat osteoarthritis, which is common to 200 million people?

*Only for medical professionals to read the reference collection! In line with the original intention of "spreading the strongest rheumatism and creating a new academic fashion", on the occasion of saying goodbye to the old and welcoming the new, the "medical world" media teamed up with 4 top domestic rheumatism and immunology departments and invited 17 well-known experts in the field of rheumatism, covering 8 rheumatism In the field of hot diseases, we will start the “Rheumatism and Rheumatism Annual Inventory in 2020”.

What I brought to my colleagues in the Department of Rheumatology and Immunology in front of the screen today is the "Progress in Diagnosis and Treatment of Osteoarthritis in 2020" shared by Professor Xie Xi from the Department of Rheumatology and Immunology, the Second Xiangya Hospital of Central South University.

01OA patients, 400 million in 2030? Osteoarthritis (OA) is a group of heterogeneous diseases characterized by articular cartilage damage and bone hyperplasia at the edges of joints caused by a variety of factors.

 OA tends to occur in middle-aged and elderly people, and the incidence increases with increasing age.

The incidence of OA in women is about twice that of men.

According to statistics, 15.
5% of OA patients over 60 years old in my country are estimated to reach 400 million in 2030.

 Looking back on 2020, what are the progress in diagnosis and treatment of osteoarthritis? Professor Xie Xi shared the latest progress in diagnosis and treatment of OA from the research progress of the etiology and mechanism of OA, pathological changes, and treatment progress.

02 The etiology is not clear, but it is related to lifestyle.
In the past, OA was considered to be a degenerative disease of bones and joints.
Now it is often considered that OA is also an inflammatory disease.

The etiology of OA is not clear, and it is related to trauma, age, metabolism, diet, gender, immunity, and lifestyle.

 Professor Xie Xi mentioned that there are many risk factors that lead to OA, including stress inflammation and metabolic inflammation caused by the environment, sedentary lifestyle, high-calorie low-fiber diet, etc.

 1 The pathogenesis of aging and OAOA is not yet fully understood.

Studies have shown that under age-related stress, joint cells (chondrocytes, bone cells and synovial fibroblasts) exhibit senescence-related secretory phenotypes (SASP).

SASP has been confirmed to be related to cartilage degradation and OA.

SASP can secrete a variety of chemokines, cytokines, proteases and growth factors, thereby mediating various pathophysiological processes of OA.

Second, senescent joint cells can erode telomeres, leading to increased expression of p53 and cyclin-dependent kinase (CDK) inhibitors p21 and p16, increased production of reactive oxygen species (ROS), and the appearance of aging-related heterochromatin.

 Figure 1: Aging and OA 2 Trauma and OA joint tissue damage on the one hand activates the immune system and removes necrotic tissue and senescent cells; on the other hand, trauma can cause cell senescence and activate SASP.

Senescent cells can be widely distributed in joint tissues (including articular cartilage, subchondral bone, subpatellar fat pad), secrete SASP-related inflammatory factors, and induce inflammation.

 Professor Xie Xi summarized 3 tips on the etiology, pathogenesis and risk factors of OA: OA is not only a degenerative disease, but also an inflammatory disease.

The expression of inflammatory cytokines is up-regulated in the lesion.

OA is not only a cartilage disease, but also affects the entire joint disease including subchondral bone, joint capsule, synovium and tissues around the joint.

SASP plays an important role in the pathophysiology of OA.

022019 China Guide vs Foreign Guide Professor Xie Xi first interpreted the domestic and foreign guides.

 The recommendations of the "Guidelines for the Diagnosis and Treatment of Osteoarthritis in China in 2019" are as follows: 1.
OA diagnosis: based on clinical manifestations, excluding other types of joint diseases.

2.
OA assessment: Comprehensive assessment of OA risk factors (weight, inflammation, metabolism, etc.
), affected joint locations and clinical manifestations.

3.
OA treatment goals: relieve pain, prevent joint deformation, improve joint function and improve the quality of life.

4.
OA weight control: It is recommended that OA patients control their weight, and those who are overweight or obese should lose weight. 5.
OA self-management: OA patients should reduce prolonged standing, kneeling or squatting, climbing stairs, etc.

Patients with OA should perform reasonable joint muscle training and moderate aerobic exercise.

According to the disease part, choose the corresponding exercise mode, such as the grasping activity of the hand joint, the knee flexion and extension activity under non-weight bearing conditions, and the gentle activity of the cervical and lumbar joints in different directions.

6.
OA topical medication: For mild pain, it is recommended to use non-steroidal anti-inflammatory drugs (NSAIDs) preparations for external use.

7.
OA physical therapy: Tuina, massage, acupuncture and other methods.

8.
Glucosamine or chondroitin sulfate: There is no improvement in symptoms for 3 to 6 months and can be stopped.

9.
Oral NSAIDs: For patients with persistent pain or moderate to severe pain, it is recommended to use the lowest effective dose of NSAIDs orally after the risk assessment.

10.
OA treatment with traditional Chinese medicine.

11.
Intra-articular injection of glucocorticoid: For knee OA with persistent or moderate to severe pain, intra-articular injection of glucocorticoid is recommended.

12.
Intra-articular injection of HA: For knee OA with persistent or moderate to severe pain, intra-articular injection of HA can be considered.

 In 2019, the European Society of Osteoporosis and Osteoarthritis Clinical and Economics (ESCEO) and the International Society for Osteoarthritis Research (OARSI) updated the guidelines for treatment of knee OA, and the comparison of the two drug treatments is as follows: 1.
External NSAIDs: OARSI recommended as First choice; ESCEO ranked it after glucosamine/chondroitin sulfate and paracetamol treatment.

2.
Paracetamol: OARSI is not routinely recommended; ESCEO recommends short-term low-dose (≤3 g/day) application.

3.
Glucosamine/chondroitin sulfate: Not recommended by OARSI; ESCEO recommends the use of medicinal grade.

4.
Opioids: OARSI does not recommend the use; ESCEO recommends short-term weak opioids to treat symptoms that do not relieve OA.

Immediately afterwards, Professor Xie Xi shared the latest OA drug treatment progress.

 In 2021, Latourte et al.
reviewed the research progress of osteoarthritis drugs in the journal Nature Review Rheumatology, including the following potential treatment drugs for OA.

 1.
Medications to relieve OA pain Cartilage itself does not contain nerve endings, but the subchondral bone, synovium, and periarticular tissues have pain receptors distributed.

OA pain involves central and peripheral sensitization.

 Anti-nerve growth factor (NGF): NGF is a key neurotrophic factor involved in peripheral sensitization.

Subcutaneous injection of anti-NGF neutralizing antibodies (tanezumab, fasinumab) can improve hip and knee OA pain and function, but there is a risk of rapid progression of OA.

Inhibition of NGF receptor tropomyosin-related kinase A (TrkA): ASP7962 (oral), GZ389988A (articular cavity injection).

Transient receptor potential cation channel subfamily V member 1 (TRPV1, capsaicin receptor) desensitization therapy: Capsaicin will continue to stimulate TRPV1, reduce membrane excitability, and decrease painful afferents (desensitization phenomenon).

Injecting synthetic trans-capsaicin CNTX-4875 into the joint cavity can relieve knee joint OA pain.

Other TRPV1 regulators include NEO6860 and so on.

2 Inhibit cartilage destruction and promote cartilage repair drugs OA cartilage loss is mainly due to the imbalance of cartilage cell anabolism and extracellular matrix (ECM) decomposition.

Inhibiting ECM degradation enzymes are proteoglycanase ADAMTS5 inhibitors, including oral small molecule drugs GLPG1972/S201086, and subcutaneously administered neutralizing antibodies (M6495).

UBX0101, etc.
, can be used to remove senescent cartilage cells.
At present, clinical trials have initially found that the drug has a certain inhibitory effect on cartilage damage.

The drugs that promote cartilage synthesis ECM include Sprifermin (rhFGF18, intra-articular administration) and TissueGene C (specific expression of TGF-β chondrocytes, intra-articular injection).

3 Targeted drugs to inhibit subchondral bone remodeling Subchondral bone remodeling is the core feature of OA, so it is important to inhibit subchondral bone remodeling.

 Bisphosphonates: inhibit bone resorption by targeting osteoclasts.

Cathepsin K inhibitor: Oral cathepsin K inhibitor MIV-711 can inhibit knee OA cartilage damage and bone remodeling.

Wnt signaling pathway inhibitor: Lorecivivint (intra-articular Wnt inhibitor), a potential DMOAD, is being studied for the treatment of knee OA.

4 Anti-OA synovial inflammation drugs OA cartilage fragments and ECM components can be released into the joint cavity to promote inflammation of synovial cells with damage-related molecular patterns (DAMPs) and release various inflammatory mediators (complement, cytokines, chemokines, etc.
) ) To further enhance cartilage catabolism and cause continuous cartilage destruction.

Stimulated chondrocytes and fat pads around joints also secrete inflammatory mediators.

Anti-IL-1β and anti-TNF treatment of knee OA: It can't improve the symptoms of OA in the short term, but it may improve joint damage in the long term.

 5 Articular cavity injection of knee OA.
Most guidelines do not recommend intra-articular injection of hyaluronic acid, but recommend intra-articular injection of glucocorticoid.

(See Table 1) Table 1: Recommendations for hyaluronic acid and glucocorticoid acid in different guidelines 03 Discussion Finally, the meeting entered the discussion session.

 Some netizens raised a question: In 2019, ESCEO and OARSI have different treatment recommendations for OA.
How should they choose clinically? Professor Xie Xi said that the two guidelines target different patient populations, so the treatment recommendations for OA are different.

We also need to choose a treatment plan based on the specific actual situation of OA patients in my country.
For details, please refer to the "2019 Chinese Osteoarthritis Diagnosis and Treatment Guidelines".

More attention and attention should be paid to the non-drug treatment of OA, and more health education should be given to patients.

At the same time, it can also be combined with the relevant OA treatment methods of the motherland medicine to effectively control OA.

 Expert profile Professor Xie Xi Deputy Director, Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, Member of the Youth Committee of the 11th Committee of Chinese Medical Association Rheumatology Branch Member of the 6th Professional Committee of Rheumatology and Immunology of Hunan Medical Association Member of the Cross-Strait Medical and Health Exchange Member of the Infectology Group of the Professional Committee of Rheumatology and Immunology of the Association Member of the Professional Committee of Pulmonary and Vascular Disease Health Management of Hunan Province Member of the Rare Disease Professional Committee of Hunan Genetics Society, Standing Director of the First Rheumatology Branch of Hunan Health Service Association, PBL Case of China Medical Education The executive editor of the library presided over and participated in a number of national and provincial natural science fund projects, published more than 20 papers, and participated in the editing of 4 medical (translation) books.

Won a number of provincial school awards