DÄ internationalArchive9/2010The Epidemiology, Etiology, Diagnosis, and Treatment of Osteoarthritis of the Knee

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The Epidemiology, Etiology, Diagnosis, and Treatment of Osteoarthritis of the Knee

Dtsch Arztebl Int 2010; 107(9): 152-62. DOI: 10.3238/arztebl.2010.0152

Michael, J W; Schlüter-Brust, K U; Eysel, P

Background: Osteoarthritis is the most common joint disease of adults worldwide. Its incidence rises with age. Both intrinsic and extrinsic risk factors promote its development. In men aged 60 to 64, the right knee is more commonly affected; in women, the right and left knees are affected with nearly equal frequency.
Methods: The PubMed, Medline, Embase and Cochrane Library data-bases were selectively searched for current studies (up to September 2009; case reports excluded) on the epidemiology, etiology, diagnosis, staging, and treatment of osteoarthritis of the knee. The search terms were “gonarthrosis,” “prevention,” “conservative treatment,” “joint preservation,” “physical activity,” “arthroscopy,” “osteotomy,” “braces,” “orthoses,” and “osteoarthritis knee joint.”
Results and Conclusion: Osteoarthritis is not yet a curable disease, and its pathogenesis remains unclear. The best treatment for osteoarthritis of the knee is prevention. The goal of therapy is to alleviate clinical manifestations. The therapeutic spectrum ranges from physiotherapy and orthopedic aids to pharmacotherapy and surgery.
LNSLNS Osteoarthritis is the most common disease of joints in adults around the world (1). Felson et al. reported that about one-third of all adults have radiological signs of osteoarthritis, although Andrianakos et al., in an epidemiological study, found clinically significant osteoarthritis of the knee, hand, or hip in only 8.9% of the adult population (2, 3). Knee osteoarthritis was the most common type (6% of all adults). The likelihood of developing osteoarthritis increases with age. Studies have shown that knee osteoarthritis in men aged 60 to 64 is more commonly found in the right knee (23%) than in the left knee (16.3%), while its distribution seems to be more evenly balanced in women (right knee, 24.2%; left knee, 24.7%) (3, 4). The prevalence of osteoarthritis of the knee is higher among 70- to 74-year-olds, rising as high as 40% (e2). When the diagnosis is based on clinical signs and symptoms alone, the prevalence among adults is found to be lower, at 10% (e3). The radiological demonstration of typical signs of osteoarthritis of the knee is not correlated with symptoms: Only about 15% of patients with radiologically demonstrated knee osteoarthritis complain of knee pain (e4). The incidence of the disorder among persons over 70 is estimated at 1% per year (e5).

Epidemiological studies have revealed that there are both endogenous and exogenous risk factors for osteoarthritis (Table 1 gif ppt). Genetic factors unquestionably play a role. In a clinical study involving female twins, Spector et al. showed an effect of heredity on the development of osteoarthritis of the hip and knee (e6). In only very few cases, however, can osteoarthritis be attributed to the effect of a single gene. Its development and progression are more likely due to an interaction among multiple genes, in combination with further risk factors. Cross-sectional studies have shown that the risk of knee osteoarthritis is 1.9 to 13.0 times higher among underground coal miners than in a control population (e7e9); presumably, the main risk factor in this occupational group is frequent work in the kneeling or squatting position. Construction workers, too, particularly floorers, have a significantly elevated prevalence of knee osteoarthritis (e10). In another epidemiological study, Grotle et al. found a significant dose-effect relationship for overweight (BMI >30) as a risk factor for knee osteoarthritis, but not for hip osteoarthritis (e11).

The present article will discuss osteoarthritis of the knee on the basis of a selective review of relevant scientific and clinical publications and an intensive evaluation of current data from clinical trials. The information given here should enable the reader to

• recognize the risk factors for osteoarthritis of the knee,
• be familiar with the diagnostic tests used to demonstrate it, and
• know how it can be prevented and what joint-preserving treatment options are available.

Etiology
Knee osteoarthritis is classified as either primary (idiopathic) or secondary. Among the various structures making up the knee joint, the hyaline joint cartilage is the main target of the harmful influences that cause osteoarthritis and the structure in which the disease begins. 95% of hyaline cartilage consists of extracellular matrix. Otte et al. coined the term “organ of articulation” to emphasize the common functional purpose of all structures composing the joint (5), from its bony components covered with hyaline cartilage to its -capsule, ligaments, and menisci, and the muscles that move it. A list of etiologies of secondary osteoarthritis of the knee can be found in Box 1 (gif ppt).

Pathophysiology
The dynamic equilibrium between the continual, ongoing formation and breakdown of the cartilaginous matrix is regulated by an interplay of anabolic influences (e.g., insulin-like growth factors [IGF] I and II) and catabolic influences (e.g., interleukin-1, tumor necrosis factor [TNF] alpha, and proteinases). To a limited extent, these mechanisms can eliminate or compensate for the harmful influences that cause osteoarthritis by stimulating and modifying the metabolic activity of chondrocytes. When these harmful -influences exceed the system’s ability to compensate, however, matrix degradation occurs; this is the first step in the development of osteoarthritis, which can progress to advanced disease (Figure 1 gif ppt). Why cartilage degenerates is not yet well understood. Mechanical and enzymatic factors are thought to impair chondrocyte function and damage the matrix (e12, e13) (Figure 2 gif ppt).

Diagnostic evaluation
The main goal of diagnostic evaluation is to demonstrate the presence of osteoarthritis unequivocally, or else to rule it out. A precise diagnosis enables precise treatment. The major elements of the diagnostic evaluation are the history, physical examination, imaging studies, and, in some cases where special questions arise, laboratory testing.

History
Patients suffering from osteoarthritis often complain of pain on movement, typically occurring when movement is initiated or when the patient begins to walk. The pain is often described as a dull ache. As osteoarthritis progresses, the pain becomes continuous, and the functionality of the joint is severely impaired. Historical criteria that are relatively specific for osteoarthritis, but can also be found in other joint diseases, are listed in Box 2 (gif ppt).

Physical examination
Each stage of the disorder has its own characteristic physical findings. Knee pain is the leading symptom, usually becoming worse when the affected knee is put in motion and improving when it is at rest. Persistent pain at rest, or at night, can be a sign of advanced osteoarthritis. The physical examination should incorporate all relevant findings, including findings on inspection and palpation, testing of the range of movement, and special functional tests when needed (e.g., ligament stability, meniscus tests, gait analysis). The physical examination of the knee ligaments consists of the following:

• testing of the lateral ligaments with varus or valgus stress, and
• testing of the anterior and posterior cruciate ligaments with the drawer test.

Likewise, the menisci should be diagnostically tested manually, and the femoropatellar joint should be assessed for signs of irritation and for normal patellar mobility. In the Zohlen test, the patient’s knee is extended, and the examiner gently presses the patella into the trochlear groove while asking the patient to tense the extensor muscles of the thigh (quadriceps femoris). If this maneuver causes pain, the test is positive. Limping revealed by gait analysis may be due to shortening of one leg.

Imaging studies
X-ray imaging studies are used both for primary diagnosis and to assess the progression of the disease. Plain films should be obtained in standardized fashion in at least two planes (a-p and lateral) (Figure 1). Special functional plain films can be obtained as well to answer specific diagnostic questions. The typical radiological signs of knee osteoarthritis that can be seen on plain films are incorporated in the staging system of Kellgren (6) (Box 3 gif ppt).

Supplementary radiological studies can include MRI, to demonstrate the hyaline cartilage, as well as 99mTc bone scanning, to assess metabolic activity in the subchondral bone. These tests do not appear to yield much additional useful information. Ultrasonography is a good way to demonstrate the soft tissues and fluid-filled spaces, but it is highly examiner-dependent, and much experience is needed for the proper assessment of its findings.

Staging
The clinical symptoms and signs of osteoarthritis and its radiological correlates follow a typical course as the disease progresses and can thus be incorporated into a clinically useful staging system. The WOMAC osteoarthritis index (7), for example, reflects the clinical severity of the disease. Though not commonly used in routine clinical practice, the WOMAC index permits a valid, reproducible assessment of the degree of impairment by pain and loss of function. A number of different joint-specific scoring systems have been developed (8); they vary with respect to the weighting of subjective and objective criteria.

Treatment
Osteoarthritis is not a curable disease at present, as the mechanism by which it arises and progresses remains incompletely understood. Therefore, the goal of treatment is to alleviate the signs and symptoms of the disease and, if possible, to slow its progression. The therapeutic spectrum ranges from general measures to physiotherapy, orthopedic aids and orthoses, pharmacotherapy, and finally surgery and rehabilitation. As Mohig et al. stated, “The best treatment for knee osteoarthritis is prevention” (e15). Surgery is indicated when the patient’s symptoms accord with the physical and radiological findings and all conservative treatments have been exhausted. A helpful therapeutic algorithm for osteoarthritis of the knee, which the authors have used successfully at their institution, is shown in Figure 3 (gif ppt).

Conservative treatment
The conservative treatment of knee osteoarthritis is based on a stepwise therapeutic scheme (Box 4 gif ppt), which is to be applied individually depending on the severity and distribution of symptoms as well as any possible accompanying illnesses (9, e16). A guideline for the treatment of osteoarthritis of the knee (e17) has been issued jointly by the German Society for Orthopedics and Orthopedic Surgery (Deutsche Gesellschaft für Orthopädie und orthopädische Chirurgie) and the German Professional Association of Orthopedists and Trauma Surgeons (Berufsverband der Ärzte für Orthopädie und Traumatologie). The goals of treatment, as stated in the guideline, are:

1. Pain relief
2. Improved quality of life
3. Improved mobility
4. Improved walking
5. Delayed progression of osteoarthritis

The guideline does not contain any assessment of the individual conservative measures mentioned, nor does it contain stage-specific recommendations for conservative treatment. A summary of published studies on the non-pharmacological treatment of knee osteoarthritis, with their results and levels of evidence according to the criteria of evidence-based medicine (CEBM, [e18]), is given in Table 2 (gif ppt).

An extensive discussion of each type of conservative treatment would be beyond the scope of this article, which is intended to provide an overview of all potentially applicable treatments.

General measures
These include patient education, lifestyle adjustment, and, when indicated, weight loss. Any factors placing excessive and damaging stress on the knee joint should be eliminated, if possible. For example, with regard to sports, the patient might be advised to switch from Alpine (downhill) to Nordic (cross-country) skiing. For any type of sport, good, adequately shock-absorbing shoes are important, as are the proper training equipment and correct performance of the sport. Chodosh et al., in a meta-analysis (evidence level Ia), found that general measures have no appreciable effect on pain and function in knee osteoarthritis (e19). A further meta-analysis of 16 controlled trials (e20) yielded the finding that individual exercise and self-management had a moderate, but clinically significant psychological effect and made a positive contribution to the patients’ emotional well-being.

Physiotherapeutic measures
Physiotherapy for knee osteoarthritis includes exercise therapy as well as physical measures, including the following:
ultrasound application (to relieve pain and support endogenous healing processes)

• electrotherapy
• muscle stimulation
• application of heat and cold
• transverse friction (a special massage technique)
• acupuncture
• stretching/walking
• traction.

Pollard et al. showed that manual therapy reduces pain and improves function significantly, in comparison to a control group (evidence level II) (10). An analysis of 17 randomized controlled trials (evidence level Ia) showed that pain could be relieved, and function improved, by either individualized or group therapy (e20, e21). No particular treatment program was found to yield better results than the others.

Orthopedic aids and orthoses
Sometimes, an orthopedic aid or orthosis is necessary. Orthopedic aids include, among others, cushioned heels (providing a shock-absorbing function) and wedges to elevate the inner or outer side of the shoe, thereby correcting the axis to a certain extent and taking mechanical stress off the affected part of the joint. Some patients initially do not want to accept these aids, but can be made more amenable to them by adequate patient education and the active involvement of orthopedic technicians and shoemakers. Knee orthoses are also intended to relieve pain and improve joint function (11). In a Cochrane Review, five controlled trials (evidence level Ib) were evaluated (e22). Patients wearing an orthosis were found to have significantly less pain and better function than patients in the control groups.

Pharmacotherapy
The following classes of medications are currently used to treat osteoarthritis of the knee:

• analgesics/anti-inflammatory agents
• glucocorticoids
• opioids
• symptomatic, slow-acting drugs for osteoarthritis (SYSADOA)
• anti-cytokines.

The specific risks associated with the use of classic non-steroidal anti-inflammatory drugs (NSAIDs) are due to their mechanism of action, i.e., the inhibition of prostaglandin secretion through the inhibition of cyclooxygenase (COX) in one or both of its two isoforms, COX-1 and COX-2. Specific inhibitors of COX-2 have a selective anti-inflammatory effect but are still markedly nephrotoxic. Nonselective COX inhibitors also have renal side effects. The Cochrane database contains a review of 16 randomized trials (evidence level Ia) (e23); yet, despite the large number of studies, the efficacy and safety of these drugs cannot yet be judged conclusively.

When signs of inflammation arise, intra-articular glucocorticoid injections can very rapidly eliminate a joint effusion. The most suitable type of glucocorticoid for injection has been found to be one with a long half-life, in crystalloid solution, with a small crystal size (e.g. triamcinolone acetonide or hexacetonide, at a dose of 10 mg or 40 mg, respectively). Steroid injections should be used with caution in diabetic patients who are already hyperglycemic. All joint punctures and injections must be performed with the proper sterile technique, as described in the guidelines. In a meta-analysis (evidence level Ia) of the efficacy of intra-articular corticosteroid injections compared to placebo, hyaluronic acid, and lavage, it was found that corticosteroid injections significantly reduced pain two weeks after the injection (RR 1.81) and three weeks after it (RR 3.11) (e24). The German professional associations have not yet issued any official recommendation about the duration and frequency of intra-articular corticosteroid injections. Their guidelines are currently being updated. On the other hand, the current guidelines of the American Academy of Orthopaedic Surgeons (AAOS) recommend that intra-articular corticosteroid injections for the treatment of osteoarthritis should be performed in the short term only (e25). Septic arthritis is a serious potential complication. In a retrospective study from Iceland, the risk of septic arthritis was calculated to be 0.037% per corticosteroid injection (e26). Thus, in Iceland, the frequency of joint infection complicating intra-articular corticosteroid injection is 1 case per 2633 injections.

In addition to the types of medications mentioned above, there is a heterogeneous group of medications that, unlike the COX-2 inhibitors, do not inhibit prostaglandin synthesis. This group includes hyaluronic acid, D-glucosamine sulphate, chondroitin sulphate, and diacerein. These medications are collectively called slow-acting drugs for osteoarthritis (SADOA), a term coined by the Osteoarthritis Research Society International (OARSI). They can be given either orally or directly into the joint. Their effect, as the term SADOA implies, is of gradual onset. These medications, in turn, are subdivided into symptomatic slow-acting drugs for osteoarthritis (SYSADOA) and the so-called disease-modifying osteoarthritis drugs (DMOAD). The mechanisms of action of the individual agents have not yet been fully elucidated; they range from inhibition of inflammation and nociceptor blockade to a potential alteration of the viscoelastic properties of cartilaginous tissue. Towheed et al. found that these drugs slow the radiological progression of knee osteoarthritis (e27). In a randomized, controlled, double-blind trial, Petrella et al. (12) found that patients with knee osteoarthritis treated with intra-articular injection of hyaluronic acid had significantly less pain and better function for up to three weeks afterward (evidence level I). No severe systemic side effects were reported.

A number of drugs for osteoarthritis are intended to counteract the pro-inflammatory, matrix-destroying effect of cytokines. Further treatment approaches include the administration of antibodies against TNF-α (which are currently available) or the use of anti-inflammatory enzymes such as IL-4, IL-10, IL-13 and TNF-β (13).

For the sake of completeness, mention is also made of other treatment approaches such as ointments, herbal and homeopathic remedies, leeches, and special diets containing gelatin and amino sugars. The efficacy of these treatments seems questionable.

Surgery is indicated only when all conservative measures have been tried without success, in patients with advanced osteoarthritis and severe subjective impairment from their symptoms (Box 5 gif ppt).

Surgery
The overwhelming majority of intra-articular operations are performed through an arthroscope. The main advantages of arthroscopic procedures are minimal operative trauma and a very low infection rate (under 0.1%). Mosley et al. assessed the efficacy of arthros-copy in a randomized, placebo-controlled trial (evidence level I) (14). The patients in this trial were assigned to one of three groups:

Group 1: arthroscopic debridement
Group 2: arthroscopic lavage
Group 3: placebo group with a skin incision only.

24 months after the procedure, the results in groups 1 and 2 were not significantly better than those in group 3. It was pointed out that the findings do not give any indication of the role of placebo effects in surgical outcome, or whether other, independent effects are at work.

Arthroscopic lavage was described as early as 1934 by Burmann (15). The purpose of this technique is to rid the joint of detritus and inflammatory mediators. Its probability of success as an individual procedure cannot be judged, because it is usually performed today concomitantly with other intra-articular maneuvers in the same operative sitting.

Shaving, also called chondroplasty, involves removing frayed and fragmented cartilage (Outerbridge stages 2 and 3) and smoothing the edges (16). This technique, too, has been found to yield no more than a short-term benefit.

Debridement, described in 1941 by Magnuson (17) as “house-cleaning arthroplasty,” serves the same general purposes. It is also useful for the treatment of possible meniscal damage, the removal of free-floating bodies within the joint, and the reduction of symp-tomatic osteophytes.

The goal of bone-stimulating techniques is to open the subchondral cartilage and thereby bring pluripotential stem cells to the joint surface, where they are then supposed to form fiber bundles under the influence of mechanical and biological forces. Studies have not revealed any significant differences between the various methods that are used (18).

Autologous chondrocyte transplantation was described in 1984 by Brittberg. In this technique, cartilage cells are taken from the joint, enzymatically isolated and cultured ex vivo, and then put back into the joint at the site of the cartilage defect, which is prepared (“freshened up”) before the cultured cells are added (19). Long-term results are not yet available to document the survival of the reimplanted cartilage cells (20).

In autologous osteochondral transplantation (OCT), also called mosaicplasty, cylinders of cartilage and bone are taken from a part of the joint that is not affected, and then inserted into the cartilage defect with press-fit technology. In principle, OCT can be performed through an arthroscope, unless the defect is too large (21). An important finding is that fibrocartilage is macroscopically demonstrable at the interface between the osteochondral cylinder and the native local tissue; thus, solid integration is not present (22). The reported results of OCT are, in general, very promising. For example, the rate of good or very good outcomes was 92% in a prospective clinical trial performed by Hangody et al. (evidence level II) (23). 81 of the 98 follow-up arthroscopies that were performed revealed congruent surfaces as well as the histologically verified survival of the transplanted osteochondral cylinders.

Corrective osteotomy near the knee joint can be performed in the frontal, sagittal, or transverse plane, in either the distal portion of the femur or the proximal portion of the tibia (i.e., just above or just below the knee). The goal of such operations is to “tip” the -affected portion of the joint out of the zone of excessive mechanical stress, redirecting the weight-bearing axis toward the portion of the joint that is still largely intact. Procedures can be classified as either subtractive (tending to narrow the joint) or additive (tending to widen it). The upper limit for additive correction is 8°, according to Jakob (24). If a stronger correction is needed, a subtractive procedure is advised. The indispensable elements of all such operations are a correct determination of the indication for surgery and optimal planning of the procedure to prevent primary over- or undercorrection. The reported results are, in general, good over the intermediate to long term (25). Corrective osteotomy is said to provide the benefit of making the patient able to participate in sports again, though there have been cases in which the correction was lost in further postoperative follow-up (e28). In 2007, a Cochrane Review of 13 randomized controlled trials documented significantly improved knee function and reduced pain. There has not been any study to date, however, in which corrective osteotomy near the knee joint is compared to conservative treatment (e29).

Overview
There are many treatments for knee osteoarthritis. Prevention is important: If the influences that can potentially damage the knee are eliminated early enough, then the development of osteoarthritis can be prevented, or at least the progression of any changes that are already present can be slowed. Patient education and counseling are the first step in any treatment plan and should include information about the course of the disease and the range of treatment options. A stepwise treatment algorithm should be applied, in order to slow the progression of the disorder and thereby grant the patient the best possible quality of life. Even though, for many forms of treatment, the clinical trials performed to date have shown only limited efficacy, this does not imply that these treatments should be abandoned. The best treatment for each patient should be chosen after an individual assessment of the severity of knee osteoarthritis and an individual evaluation of the risks. An important general principle is that surgery should be performed only when conservative treatment has failed.

Conflict of interest statement
The authors declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.

Manuscript submitted on 15 April 2009; revised version accepted on 21 December 2009.

Translated from the original German by Ethan Taub, MD.


Corresponding author
PD Dr. med. Joern W.-P. Michael
Klinik und Poliklinik für Orthopädie und Unfallchirurgie
Universität zu Köln
Joseph-Stelzmann-Str. 9
50931 Köln, Germany
joern.michael@uk-koeln.de

@For e-references please refer to:
www.aerzteblatt-international.de/ref0910
A case report is available at:
www.aerzteblatt-internationel.de/article09m0152
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Geirsson AJ, Statkevicius S, Víkingsson A.: Septic arthritis in Iceland 1990–2002: increasing incidence due to iatrogenic infections. Ann Rheum Dis. 2008; 67: 638–43. MEDLINE
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Brouwer RW, van Raaij TM, Bierma-Zeinstra SMA, Verhagen AP, Jakma TT, Verhaar JAN: Osteotomy for treating knee osteoarthritis. Cochrane Database Syst Rev 2007; 3: CD004019
Klinik und Poliklinik für Orthopädie und Unfallchirurgie, Universität Köln: PD Dr. med. Michael, Dr. med. Schlüter-Brust, Prof. Dr. med. Eysel
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