arthrosis

from Wikipedia, the free encyclopedia
Medial osteoarthritis of the knee MR image of an arthritic knee joint . The osteophytes in the medial (central) and lateral (lateral) area of ​​the joint space and the wear and tear of the cartilage layer in the left area of ​​the picture can be clearly seen . The bone of the tibial head in the central area is compressed, a reaction to the increased mechanical stress. The cartilage layer has lost its cushioning function.

The term arthrosis or arthrosis ( synonym arthrosis deformans - from ancient Greek ἄρθρον arthron , joint 'and Latin deformare , mutilate') describes a degenerative joint disease ( joint wear ) and is also referred to as joint wear that exceeds the normal age range .

The causes are seen as excessive stress (e.g. increased body weight ), congenital or traumatic causes such as misalignment of the joints or bony deformity due to bone diseases such as osteoporosis . Osteoarthritis can also arise as a result of another disease, for example joint inflammation (arthritis) ( secondary osteoarthritis ) or be associated with overuse-related effusion (secondary inflammatory reaction ) ( activated osteoarthritis ). Osteoarthritis is also known as osteoarthritis ( osteoarthrosis ) and among others in the Anglo-American literature osteoarthritis referred (OA), not to be confused with rheumatoid arthritis (Engl. Rheumatoid arthritis , RA), a chronic inflammatory autoimmune disease of the joints.

In principle, all joints can be affected by arthritic changes. In Germany, the disease is most often localized in the knee joint . Osteoarthritis is one of the most frequent consultation occasions in a general medical practice. Around five million people in Germany suffer from osteoarthritis. It is the most common joint disease (arthropathy) worldwide .

Classification

Classification according to ICD-10
M15-M19 arthrosis
M47 Spondylosis (including osteoarthritis or osteoarthritis of the spine, degeneration of the articular surfaces)
ICD-10 online (WHO version 2019)

A basic distinction is made between primary and secondary osteoarthritis.

In the case of primary osteoarthritis , a biological inferiority of the cartilage tissue is assumed for an unclear cause. Secondary osteoarthritis occurs as a result of mechanical overload (e.g. in the case of hip dysplasia ), inflammatory changes (e.g. in the case of arthritis) or metabolic disorders ( e.g. in the case of chondrocalcinosis ). The frequency distribution of both forms is controversial.

In osteoarthritis, an initial damage to the cartilage leads to changes in the bone as it progresses:

  • In stage 4, the bone plate of a joint flattens out. In order to absorb the pressure on the joint anyway, marginal bulges (osteophytes) form on the bone.

causes

Hip joint - the main mechanical stress zone is shown in blue.
Hip joint dysplasia - the main mechanical stress zone is significantly smaller than the normal variant.

In principle, osteoarthritis is also differentiated according to its cause. The arthrosis alcaptonurica is an increased deposition of homogentisic in joints with pre-existing Alkaptonurie basis. In haemophilic osteoarthritis, there is regular intra-articular bleeding in haemophilia (blood joint). The arthrosis Urica is by the mechanical impact of urate crystals (uric acid) on the healthy cartilage caused.

The classic cause of osteoarthritis is dysplasia of the joints . The example of the hip clearly shows that the mechanically most stressed zone in a physiological hip position represents a significantly larger area than in a dysplastic hip. However, the loads caused by the forces acting on the joint are largely independent of the joint shape. They are essentially distributed over the main exposure zone (s). As a result, a higher pressure load will occur with a smaller zone than with a larger one. The biomechanical pressure load on the articular cartilage is thus greater with a dysplastic hip than with a physiological hip position. This law is generally seen as the cause of the frequent occurrence of arthritic changes in supporting joints that deviate from the ideal anatomical shape.

If the consequences of an injury are responsible for premature wear, one speaks of post-traumatic osteoarthritis . Mechanical, inflammatory, metabolic, chemical ( quinolone antibiotics ), trophic , hormonal , neurological and genetic reasons are discussed as further causes of secondary osteoarthritis . In most cases, the development of osteoarthritis is viewed as idiopathic , that is, without a currently tangible cause.

Medicinal causes of osteoarthritis can, for example, be antibiotics from the class of gyrase inhibitors ( fluoroquinolones such as ciprofloxacin , levofloxacin ). These drugs result in poorly vascularized tissues (hyaline articular cartilage, tendon) to a complexation of magnesium - ions , with the result that irreversible damage occurs on the connective tissue. This damage is usually more pronounced in children and adolescents in the growth phase. Tendopathies and arthropathies are known side effects of this class of drugs. According to information from independent pharmacologists and rheumatologists , these antibiotics lead to an accelerated physiological breakdown of the hyaline articular cartilage in adults . Long-term treatment with phenprocoumon can also promote osteoarthritis due to the decrease in bone density when the internal joint structure is stressed.

In addition to age, mechanical overloads, (micro) trauma, destabilization of the joints caused by loss of safety mechanisms, and genetic factors are known to be risk factors for osteoarthritis. However, neither the origin nor the options for intervention have been fully clarified.

In a joint affected by osteoarthritis, the level of nitric oxide is increased. Something similar could be observed through mechanical irritation of cartilage tissue. Mechanical forces are likely to be causally involved in the development of osteoarthritis.

Prevalence

The risk of developing osteoarthritis increases with age. About two thirds of people over the age of 65 are affected by the disease, but not all sufferers also suffer from the symptoms.

Symptoms

Osteoarthritis can be symptom-free. Start-up and stress-dependent pain are typical. The extent of the pain does not necessarily correlate with the degree of osteoarthritis that can be objectively assessed. Other typical symptoms are joint effusion (activated osteoarthritis), increasing deformation (deformation) of the joint and joint noises due to increasing unevenness of the cartilage surface when moving.

Diagnosis

CT image of osteoarthritis of the sacroiliac joint (sacrum-iliac joint)
Schematic representation of the radiological signs of hip arthrosis:

(1) (marginal) osteophyte
(2) subchondral sclerosis
(3) rubble cyst
(4) narrowing of the joint space

The patient reports joint pain in the anamnesis , after which it has to be clarified on which occasions this pain occurs. This is followed by a clinical examination of the joint contour, the function, the ligament stability, the surrounding muscles and then, depending on the requirements, diagnostic imaging such as X-ray , computed tomography (CT) or magnetic resonance imaging (MRT). Signs of existing osteoarthritis are narrowing of the joint space, sclerosis (reactive bone compression on both sides of the joint space), osteophyte formation at the joint margins and subchondral cyst formations of the joint-forming bone, which are caused by fine cracks in the cartilage and the penetration of joint fluid into the bone layer below . A narrowing of the joint space indicates arthritis or osteoarthritis, depending on whether the bone near the joint is thinned or thickened.

If a finding suggests minimally invasive intervention , an arthroscopy may be necessary. The development of arthroscopy in recent years has made a number of joints accessible for this type of surgical procedure. Arthroscopies are most often performed on the knee joint, also to clarify preoperatively, for example, which type of endoprosthesis makes sense in each individual case. Mostly, however, arthroscopies are used in order to be able to carry out the necessary repair of the joint at the same time as the diagnosis.

By further developing methods for evaluating MRI images, osteoarthritis can be detected at an early stage. This technique is also of great importance for research into new drugs as a therapy-accompanying process control.

treatment

Basically, osteoarthritis therapy pursues two goals, namely freedom from pain under normal stress and the prevention of mechanical restrictions or changes in a joint.

The following therapeutic approaches are suitable for this:

  • Freedom from pain
    • lack of stimulus for the increased development of pain mediators
    • Suppression of pain perception or the local effect of the pain mediators
  • Preventing the progression of joint changes through
    • Elimination of mechanical risk factors such as joint dysplasia or other causes that lead to increased pressure on the articular cartilage,
    • Regeneration of the articular cartilage or
    • endoprosthetic replacement of the articular surface.

Concept of "SYSADOA" and "DMOAD"

SYSADOA ( Symptomatic Slow Acting Drugs in Osteoarthritis ) are substances with no direct pain relieving effect. In principle, they do not change the course of osteoarthritis as a disease. DMOAD ( Disease Modifying Osteo-arthritis Drugs - formerly known as chondroprotective agents ) are said to influence the course of the disease. Slowing down the cartilage degeneration and / or increasing the cartilage regeneration ( remodeling ) are suitable for this.

The placebo effect

As part of a meta-analysis, the untreated control groups were compared with the placebo- treated control groups ( drug , non-drug and operative placebo treatments) from existing studies on osteoarthritis therapies . It turned out that the sham treatment was statistically significantly superior to the lack of treatment in terms of pain relief, rigidity and subjective mobility.

Operational procedures

The possibilities of therapy depend on the affected joint. For osteoarthritis of the hip (coxarthrosis), corrective osteotomies (operative joint repositioning) on ​​the thigh and pelvis and an endoprosthesis as joint replacement surgery ( arthroplasty ) are recommended as joint-preserving operations . In knee osteoarthritis of the knee (gonarthrosis), arthroscopy (possibly also an arthrotomy ) for joint irrigation, removal of mechanical irritations, synovectomy , soft tissue surgery to improve patellar guidance and joint-near osteotomies for correction in the frontal and / or sagittal plane or a tuberosity are recommended as joint- preserving operations . A unicompartmental slide prosthesis, an uncoupled bicompartmental prosthesis or a coupled bicompartmental prosthesis with and without a retropatellar replacement (possibly with patellar modeling) can be used as joint replacement.

Cartilage transplant

Autotransplant

This is a process in which well-preserved parts of the articular cartilage from marginal areas of a joint that are not under stress (especially the knee joint) are used to replace cartilage defects in main stress areas. This technique is usually performed in a conventional arthrotomy.

Autologous chondrocyte implantation

The Autologous chondrocyte implantation (ACI) or transplantation of autologous cartilage cells ( chondrocytes ) is a form of treatment with the aim of damage to the articular cartilage compensate for the progression to slow down of cartilage damage, a joint replacement delay operation and to facilitate existing pain. The process also appeared promising in 1994 in terms of long-term results. First around 200 and 300 milligrams of cartilage cells are arthroscopically removed from an unloaded area of ​​the knee joint (such as the intercondylar fossa ), then these cells are cultivated in vitro for around four to six weeks until there are enough cells to restore them to the damaged area of ​​the articular cartilage to replant. These autologous cells should adapt to their new environment by forming new, preferably hyaline, cartilage. During implantation, cartilage cells are introduced into the damaged area in connection with a membrane (outer periosteum of the tibia or biomembrane) or a framework matrix and fixed with very fine sutures or fibrin glue. The procedure is carried out depending on the size of the cartilage defect. Clinics that use it must be specially approved for this in Germany. There is evidence of the effectiveness of this method in the treatment of symptomatic cartilage defects of the knee joint.

Arthroscopic Techniques

Depending on the size of the defect, this includes various techniques, such as freshening degenerative areas of the articular cartilage by means of healing response , shaving , Pridie drilling , or the implantation of carbon pins.

Therapy for beginning and advanced osteoarthritis

In the majority of cases, therapy is only started when the osteoarthritis is already noticeably painful and has caused a significant change in the joint. Then the goal of the therapy - despite the wear and tear of the joint - is to maintain sufficient mobility and resilience of the joint for some time.

Operation, endoprosthesis (joint replacement)

Total endoprosthesis of a hip joint
  • The main operating therapies for osteoarthritis include, among others in addition to the operational joint conversion (corrective), the abrasion (also joint toilette called) and the stiffening of the joints ( arthrodesis ), in particular the artificial joint replacement ( endoprosthesis ) . In Germany, around 400,000 endoprosthetic operations were performed on the hip and knee in 2016 - and the number is rising. The average lifespan of a hip joint prosthesis is around 15 years.
  • The definitive long-term solution is always such an endoprosthesis . Complications are rare for experienced surgeons, but can have dramatic consequences (infection, material breakage, premature loosening). Loosening of the prosthesis after standing for more than ten years is not a complication, but a natural process that has not yet been prevented. The necessary replacement operations are much more complex than the primary operations and therefore also have significantly more complications. They cannot be repeated as often as desired, since more bone substance is "used" each time. Therefore, as a rule, attempts are made to delay the initial implantation until the sixth decade of life.

The “last prosthesis” in particular is often very problematic at an advanced age. Where bone substance has already been lost due to osteoporosis, fractures may even be programmed after an operation with complications that are difficult to control.

Forearm
crutch guideline-compliant measure of orthopedic technology for hip arthrosis

Conservative forms of therapy

The efficacy of therapeutic interventions for osteoarthritis is not easy, as the disease progresses alternate painless phases with painful phases. Joint mobility can also vary as the disease progresses. In the area of ​​the hip or knee joint, for example, osteoarthritis can be documented using the pain-free walking distance and joint mobility.

Conservative forms of therapy recommended by guidelines or specialist committees and / or classified as well documented

  • The first part of the treatment is a comprehensive education of the patient about the disease, its natural course and its therapeutic influence. The advice covers topics such as behavior in everyday life, physical strain at work and sport or lack of exercise , body weight, and training (especially personal exercises) to eliminate muscular deficits.

Further treatment concepts

  • In irritation of the joints with overheating and pain, cooling measures bring a short-term improvement of the symptoms.
  • Study results indicate that acupuncture is effective for chronic knee joint pain caused by osteoarthritis:
    • The results of a large-scale study by the German Substitute Funds were presented in the Deutsches Ärzteblatt and The Lancet , among others . Acupuncture was shown to be effective against pain in the knee joint caused by osteoarthritis of the knee.
    • When osteoarthritis sham acupuncture and a (treated by medical staff with at least 140 hours of training and two years of experience performed) are acupuncture more effective than a conventional guideline-compliant standard therapy for the treatment of chronic pain. This was the result of the gerac - gonarthrosis study published in December 2005 . Under the given study conditions, she found no statistically significant advantage of verum acupuncture over sham acupuncture. Since "any" acupuncture treatment was significantly more successful than conventional therapy without needle pricks, it seems reasonable to consider that either irritation of the skin with needles alone causes a pain-relieving effect and / or that conventional treatment in the context of such a study has a nocebo effect , because this particular form of therapy (needle sticks) was withheld from the control group .
  • A therapy option provides the interleukin-1 - antagonist therapy: will be obtained an IL-1 antagonist from the patient's blood, which is injected into the affected joint. The efficacy and safety of this therapy for osteoarthritis was investigated in two randomized placebo-controlled studies. The GOAT study at the University of Düsseldorf showed in 376 patients that interleukin-1 antagonist therapy was significantly superior to hyaluronic acid and placebo treatment after 6 and 24 months. A Dutch study was able to show that the IL-1 antagonist compared to a placebo improved joint function significantly after one year and the medication intake was reduced, but the WOMAC pain score did not differ from the placebo treatment. The German Society for Rheumatology advises against treatment, as both the basic studies and the clinical studies are inadequate. Wolfgang Becker-Brüser from the pharmacritical drug telegram says: "As soon as I inject something into a joint, even if it is only saline, I create a buffer. This initially reduces the symptoms. However, the effects do not last long." The result: patients will come back soon and want another Orthokine treatment.
  • Hyaluronic acid: The abrasion of cartilage substance is reduced by "synovial fluid" called hyaluronic acid naturally produced by the undamaged joint . The degeneration process should also be able to - at least partially - be reduced or even stopped during a permanent indication. The preparation must be injected intra-articularly, with the fundamental risk of joint infection.
  • The substances glucosamine (especially in combination with MSM ) and chondroitin can improve the symptoms of osteoarthritis somewhat or delay their further progression if the disposition is positive. Results over twelve weeks ( effectiveness results of a prototypical 12-week, double-blind, randomized placebo-controlled trial of glucosamine ), on the other hand, showed that glucosamine apparently cannot be effective in osteoarthritis of the knee in such a short time. Another dietary supplement that seems promising is S-adenosyl methionine . Smaller studies claim it is just as effective as nonsteroidal anti-inflammatory (anti-inflammatory) pain relievers (ibuprofen, diclofenac, etc.) at reducing pain, although it takes about four weeks for this effect to set in. In a large placebo-controlled study, 572 patients were treated with glucosamine or chondroitin or a combination of both substances. The aim of the study was to find out whether any of the treatments could slow the progression of the disease. After a treatment period of 18 months, no advantage over placebo could be demonstrated in any treatment group.
  • Extracts of the mushroom Agaricus blazei Murril have shown in various studies that they are able to reduce inflammation and modulate the immune system, so that the organism's susceptibility to inflammation is reduced overall.
  • The fibroblast growth factor-18 (FGF-18) stimulates in model organisms for intra-articular injection, the formation of cartilage at. A recombinantly produced human FGF-18 is currently in clinical trials for the treatment of osteoarthritis.
  • The effectiveness of pulsating signal therapy , in which the cartilage tissue is exposed to pulsating magnetic fields, is controversial.
  • Another hypothesis is that gold implantation, in which fine gold is implanted close to the joint, should be helpful, since released gold ions should have an anti-inflammatory effect. This procedure has been used since 1996, but is not found in any of the guidelines. However, the Danish developers of the therapy have only scientifically published one pilot study . In this randomized, blinded study with 43 patients, however, there was no difference between the group with gold implants and the control group. Accordingly, no further scientific research was carried out, but the process will continue to be advertised.

Health system costs

Osteoarthritis is associated with significant costs for the health system. Diseases of the musculoskeletal system were in 2004 with 24.46 billion euros (= 10.9% ). after diseases of the circulatory system (2004: 35.27 billion euros = 15.7%) and diseases of the digestive system (33.27 billion euros = 14.8%), the third largest cost factor for the treatment of diseases in Germany. The costs for diseases of the musculoskeletal system were 6.77 billion euros (= 27.7% ). spent on the treatment of osteoarthritis. Over 96% of the costs for the treatment of OA in Germany in 2004 were incurred by people aged 45 and over; about 67.8% to people aged 65 and over.

Arthrosis (joint cover and special forms)

The following types of osteoarthritis refer specifically to the affected joint:

Activated Heberden osteoarthritis of the right index finger
X-ray of finger joint arthrosis (called Heberden's arthrosis in the end joints , Bouchard's arthrosis in the middle joints ). An inconspicuous picture in the red box on the left.

The following names of osteoarthritis describe the status and origin of osteoarthritis:

See also

literature

  • Klaus-Dieter Thomann: Effective help with osteoarthritis. TRIAS-Verlag, Stuttgart 2003, ISBN 3-8304-3094-9 .
  • Gerhard Leibold: Arthritis and Osteoarthritis. Jopp-Oesch Verlag, Zurich 2003, ISBN 3-0350-5037-6 .
  • Doris Schwarzmann-Schafhauser: Osteoarthritis. In: Werner E. Gerabek u. a. (Ed.): Encyclopedia of medical history. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 103.
  • Ludwig Heilmeyer , Wolfgang Müller: The rheumatic diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, pp. 309-351, here: pp. 346-351 ( Die degenerative joint diseases ), in particular pp. 346-348: Die Arthrosis deformans (osteoarthrosis, osteoarthritis, degenerative joint diseases).

Individual evidence

  1. ^ Robert Koch Institute (ed.): Arthrosis . (PDF). Federal health reporting. Issue 54. RKI, Berlin 2013.
  2. ^ Robert Koch Institute (Ed.): Health in Germany. Data tables. Federal health reporting. Robert Koch Institute. Berlin.
  3. ↑ W. Fink, G. Haidinger: The frequency of health disorders in 10 years of general practice. In: ZFA - Journal for General Medicine. 83, 2007, pp. 102-108, doi: 10.1055 / s-2007-968157 . Quoted from: What family doctors mainly deal with. In: MMW-Fortschr Med. 16, 2007.
  4. ↑ German Arthrosis Help: How common is osteoarthritis? Retrieved July 15, 2013.
  5. ↑ N. Arden, MC Nevitt: Osteoarthritis: epidemiology. In: Best Practice & Research Clinical Rheumatology . Volume 20, Number 1, February 2006, pp. 3-25, ISSN  1521-6942 . doi: 10.1016 / y.berh.2005.09.007 . PMID 16483904 . (Review).
  6. ↑ a b K. J. Bühling among others: Intensive course: General and special pathology. Verlag Elsevier, 2004, ISBN 3-437-42411-4 , p. 84. ( limited preview in Google book search)
  7. ^ W. Pschyrembel et al .: Clinical dictionary with clinical syndromes and an appendix Nomina Anatomica. 253rd edition. Verlag Walter de Gruyter, 1977, ISBN 3-11-007018-9 .
  8. ↑ a b c H. I. Roach, S. Tilley: The Pathogenesis of Osteoarthritis. In: F. Bronner, MC Farach-Carson (Ed.): Bone and Osteoarthritis. Volume 4, Verlag Springer, 2007, ISBN 978-1-84628-513-4 .
  9. ↑ M. Menschik, J. Neumüller, CW Steiner, L. Erlacher, M. Köller, R. Ullrich, W. Graninger, WB Graninger: Effects of ciprofloxacin and ofloxacin on adult human cartilage in vitro. In: Antimicrobial Agents and Chemotherapy . Volume 41, Number 11, November 1997, ISSN  0066-4804 , pp. 2562-2565. PMID 9371369 , PMC 164164 (free full text).
  10. ↑ M. Egerbacher et al .: Ciprofloxacin causes cytoskeletal changes and detachment of human and rat chondrocytes in vitro. In: Arch. Toxicol. 73, 2000, pp. 557-563. PMID 10663387 .
  11. ↑ H. Chang et al: Pefloxacin-induced arthropathy in an adolescent with brain abscess. In: Scand J Infect Dis. 28, 1996, pp. 641-643. PMID 9060073 .
  12. ↑ A. Chaslerie include: Polyarthropathy in to adolescent Treated with pefloxacin. In: Therapy. 47, 1992, p. 80. PMID 1523601 . (French)
  13. ↑ P. Das ua: Nitric oxide and G proteins mediate the response of bovine articular chondrocytes to fluid-induced shear. In: Journal of Orthopedic Research. 15, 1997, pp. 87-93. PMID 9066531 .
  14. ↑ AJ Farrell, DR Blake, RM Palmer, S. Moncada: Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. In: Annals of the Rheumatic Diseases . Volume 51, Number 11, November 1992, ISSN  0003-4967 , pp. 1219-1222. PMID 1466599 , PMC 1012459 (free full text).
  15. ↑ B. Fermor et al .: The effects of static and intermittent compression on nitric oxide production in articular cartilage explants. In: Journal of Orthopedic Research. 19, 2001, pp. 729-737. PMID 11518285 .
  16. ^ X. Liu et al.: Force-mediated dissociation of proteoglycan aggregate in articular cartilage. In: Biorheology. 43, 2006, pp. 183-190. PMID 16912392 .
  17. ↑ D. Symmons et al: Global burden of osteoarthritis in the year 2000. Documentation for GBD 2000 project. World Health Organization, Geneva 2002.
  18. ↑ Joachim Grifka, Jürgen Krämer: Orthopädie trauma surgery. Springer-Verlag, 2013, ISBN 978-3-642-28874-6 .
  19. ^ New Diagnostic Tool For Arthritis Could Stop Irreversible Damage. In: sciencedaily.com. April 27, 2013, accessed January 22, 2015 .
  20. ↑ a b C. Fassl u. a .: SYSADOA / DMOAD concept relies on slow positive effects. ( Memento from November 2, 2012 in the Internet Archive ) In: Rheuma Plus. 1, 2005.
  21. ↑ a b SYSADOA or DMOAD in osteoarthritis therapy. In: medmix.at . September 23, 2016, accessed February 23, 2018 .
  22. ^ W. Zhang et al: The placebo effect and its determinants in osteoarthritis - meta-analysis of randomized controlled trials. In: Ann Rheum Dis. 2008 doi: 10.1136 / ard . 2008.092015 PMID 18541604 .
  23. ↑ a b c d e S1 guidelines for coxarthrosis (2009) . In: AWMF online
  24. ↑ a b c d S1 guideline for gonarthrosis (2002) . In: AWMF online
  25. ↑ M. Brittberg u. a .: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. In: NEJM . 331, 1994, pp. 889-895. PMID 8078550 .
  26. ↑ P. Niemeyer, S. Andereya et al: Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group "Tissue Regeneration" of the German Society of Orthopedic Surgery and Traumatology (DGOU). In: Z Orthop accident. 151 (1), Feb 2013, pp. 38-47. PMID 23423589 . doi: 10.1055 / s-0032-1328207
  27. ↑ DB Saris et al .: Characterized Chondrocyte Implantation Results in Better Structural Repair When Treating Symptomatic Cartilage Defects of the Knee in a Randomized Controlled Trial Versus Microfracture. In: Am J Sports Med. 36, 2008, pp. 235-246. doi: 10.1177 / 0363546507311095 PMID 18202295 .
  28. ↑ Arthrosis in the knee and hip - modern endoprosthetics. District of Passau health facilities, June 10, 2016, accessed on June 27, 2017 .
  29. ↑ B. Schmid et al. a .: Efficacy and tolerability of a standardized willow bark extract in osteoarthritis patients: randomized, placebo-controlled double-blind study. In: Journal of Rheumatology. 59, 2000, pp. 314-320. doi: 10.1007 / s003930070053
  30. ↑ AM Beer et al.: Willow bark extract for osteoarthritis and coxarthrosis - results of an application observation with control group. In: Z Phytother. 29, 2008, pp. 215-222, doi: 10.1055 / s-0028-1101525 .
  31. ↑ Dieter Melchart, Andrea Streng, Andrea Hoppe, Susanne Juergens, Wolfgang Weidenhammer, Klaus Linde: Acupuncture for chronic pain: results from the model project of the substitute funds . In: Deutsches Ärzteblatt . tape 103 , no. 4 . Deutscher Ärzte-Verlag , January 27, 2006, p. A-187 / B-160 / C-159 .
  32. ↑ Claudia M. Witt, Benno Brinkhaus, Susanne Jena, Dagmar Selim, Christoph Straub, Stefan N. Willich: Effectiveness, safety and economy of acupuncture - a model project with the Techniker Krankenkasse . In: Deutsches Ärzteblatt . tape 103 , no. 4 . Deutscher Ärzte-Verlag , January 27, 2006, p. A-196 / B-169 / C-167 .
  33. ^ C. Witt et al .: Acupuncture in patients with osteoarthritis of the knee: a randomized trial. In: The Lancet. 366, 2005, pp. 136-143. doi: 10.1016 / S0140-6736 (05) 66871-7 PMID 16005336 .
  34. ↑ S. Witte u. a .: Efficacy and safety of acupuncture in chronic pain caused by osteoarthritis: multicenter, randomized, controlled study. (PDF; 1.6 MB) December 2005.
  35. ↑ H. P. Scharf et al. a .: Acupuncture and Knee Osteoarthritis - A Three-Armed Randomized Trial. In: Ann Intern Med . 145, 2006, pp. 12-20. PMID 16818924 .
  36. ↑ AW Baltzer et al .: Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. In: Osteoarthritis Cartilage. 17, 2009, pp. 152-160. PMID 18674932 .
  37. ^ P. Wehling et al .: Autologous conditioned serum in the treatment of orthopedic diseases: the orthokine therapy. In: BioDrugs . 21, 2007, pp. 323-332. PMID 17896838 .
  38. ↑ KG Yang et al .: Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial. In: Osteoarthritis Cartilage. 16, 2008, pp. 498-505. PMID 17825587 .
  39. ↑ GR Burmester and others: New version of the recommendations of the Pharmacotherapy Commission of the DGRh. In: Journal of Rheumatology. 66, 2007, pp. 83-84. doi: 10.1007 / s00393-006-0135-3
  40. ^ S. Rehart et al.: Updated statement on "Orthokine". September 2009.
  41. ↑ Controversial osteoarthritis therapy - pharmaceutical company wants to silence critical medical professionals. In: sueddeutsche.de . December 17, 2013, accessed January 22, 2015 .
  42. ↑ PR Usha, MUR Naidu: Randomized, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis . In: Clinical Drug Investigation . tape 24 , no. 6 , 2004, ISSN  1173-2563 , p. 353-363 , PMID 17516722 .
  43. ↑ N. Poolsup et al .: Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials. In: Ann Pharmacother . 39, 2005, pp. 1080-1087. PMID 15855241 .
  44. ↑ T. McAlindon include: Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from on internet-based randomized double-blind controlled trial. In: Am J Med . 117, 2004, pp. 643-649. PMID 15501201 .
  45. ^ Arthritis supplements no better than placebo. In: newscientist.com. September 30, 2008, accessed January 22, 2015 .
  46. ↑ AD Sawitzke include: The effect of glucosamine and / or chondroitin sulfate on the progression of knee osteoarthritis: A report from the glucosamine / chondroitin arthritis intervention trial. In: Arthritis & Rheumatism . 58, 2008, pp. 3183-3191. doi: 10.1002 / art.23973 PMID 18821708
  47. ↑ G. Hetland et al .: The Mushroom Agaricus blazei Murill Elicits Medicinal Effects on Tumor, Infection, Allergy, and Inflammation through Its Modulation of Innate Immunity and Amelioration of Th1 / Th2 Imbalance and Inflammation. In: Advances in pharmacological sciences. 2011. doi: 10.1155 / 2011/157015 . PMID 21912538 .
  48. ↑ EE Moore, AM Bendele, DL Thompson, A. Littau, KS Waggie, B. Reardon, JL Ellsworth: Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. In: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. Volume 13, Number 7, July 2005, pp. 623-631. doi: 10.1016 / j.joca.2005.03.003 . PMID 15896984 .
  49. ↑ D. Davidson, A. Blanc, D. Filion, H. Wang, P. Plut, G. Pfeffer, MD Buschmann, JE Henderson: Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. In: The Journal of biological chemistry . Volume 280, Number 21, May 2005, pp. 20509-20515. doi: 10.1074 / jbc.M410148200 . PMID 15781473 .
  50. ↑ clinicaltrials.gov: Study of AS902330 (rhFGF-18) Administered Intra-articularly in Patients With Knee Primary Osteoarthritis Who Are Candidates for Total Knee Replacement. Retrieved January 30, 2011.
  51. ↑ clinicaltrials.gov: A Multicenter Study of rhFGF 18 in Patients With Knee Osteoarthritis Not Requiring Surgery. Retrieved January 30, 2011.
  52. ↑ C. Zetterström, u. a .: Pivotal Advance: Inhibition of HMGB1 nuclear translocation as a mechanism for the anti-rheumatic effects of gold sodium thiomalate . In: Journal of Leukocyte Biology . tape 83 , no. 1 , October 3, 2007, ISSN  0741-5400 , p. 31-38 , doi : 10.1189 / jlb.0507323 .
  53. ↑ K. Nejrup et al. a .: Randomized controlled trial of extraarticular gold bead implantation for treatment of knee osteoarthritis: a pilot study . In: Clinical Rheumatology . tape 27 , no. 11 , May 24, 2008, ISSN  0770-3198 , p. 1363-1369 , doi : 10.1007 / s10067-008-0918-9 .
  54. ^ Federal Statistical Office (ed.): Health. Expenditures, medical expenses and personnel 2004. Federal Statistical Office, Wiesbaden, 2006.
  55. ↑ Wolfgang Miehle: Joint and spinal rheumatism. Eular Verlag, Basel 1987, ISBN 3-7177-0133-9 , p. 175.