Event Overview

Course Objective
To refresh the basics of knee care for the primary care physician and then introduce the rationale and options of knee restoration. The course will then detail the various techniques available for knee restoration with an emphasis on the specific technique of cartilage restoration using the patient's own cells which have been cultured to increase their number. After this course, the primary care physician will understand the uses and limitations of diagnostic studies for evaluating a patient with a knee problem. They will then be able assist in counseling patients regarding the multiple treatment options for their knee problem. These options will include nonoperative office knee treatments. Finally, this knowledge will also assist the physician with the decision on when to refer a patient to a knee restoration/cartilage restoration surgeon.

Knee Care and Cartilage Restoration for Primary Care Continuing Medical Education
Jack Farr, MD
Director, Cartilage Restoration Center of Indiana

Introduction
Anatomy and Physiology of The Knee
Description of basic knee anatomy
Discuss articular and meniscal cartilage form and function
History and Physical Exam
Discuss signs and symptoms of knee cartilage injury
Elaborate physical exam findings specific to knee cartilage injury
Diagnostic Studies
Discuss different forms of imaging used in diagnosis of knee cartilage injuries
Delineate when to use different imaging techniques
Treatment of Knee Cartilage Injuries
Develop treatment plan
Discuss different techniques utilized for cartilage restoration
Current technologies and future trends in cartilage restoration

Introduction
Cartilage restoration is certainly low on the list of priorities for primary care education in residency programs. Nevertheless, when patients present to a primary care physician’s office in real practice, it is very often for musculoskeletal complaints and the knee ranks just behind the back as per numbers of complaints. When examining patients with knee problems three diagnoses are most frequently seen: Arthritis, patellofemoral related pain and cartilage pathology. All three may be present in the same individual, but usually one pathology is overriding in importance for a specific office visit. The goal of this course is to allow an understanding of the underlying mechanism of disease, means of forming a differential diagnosis, which in turn allows treatment planning.

Anatomy
Knee pathology is closely tied to knee anatomy. Most physicians are familiar with knee anatomy and the distinction between the meniscal and articular cartilage. Figure 1 diagrams normal anatomy, differentiating between the medial and lateral meniscal cartilages and the three compartments of the knee: patellofemoral, medial and lateral compartments. Linking the bones are the four main ligaments: anterior and posterior cruciate ligaments and the medial and lateral collateral ligamentous complexes.

History
Patients usually present complaining of pain or loss of function. It is important to localize the pain and then relate it to specific anatomy. Usually the patient points to one of the above listed compartments. Most conditions worsening with activity and loading with the patellofemoral compartment very sensitive to stair ascension/descension. Meniscal pathology often causes focal medial or lateral joint line pain made worse with squatting or hyperflexing. This is often accompanied with the mechanical sensation of something catching in the joint. The complaint of “giving way” must be closely examined to differentiate between patellofemoral giving way with pain, giving with a loose body or meniscus displacing or giving on the basis of ligamentous instability. Patellofemoral giving is often in straight line walking while for a ligamentous deficiency to become apparent the patient is usually cutting or rapidly changing directions. Effusion and swelling are very sensitive for intra-articular pathology, but poorly sensitive for deterring a diagnosis. Articular cartilage injury may be present in all compartments and may present in association with all the above histories, yet is commonly more insidious and chronic than some of the other considerations.

Physical Examination
A systematic approach allows thorough evaluation. As the patient walks, the gait and general habitus is noted. Standing the alignment is rated as varus, valgus or neutral noting that malalignment places greater loads on the angled compartment, i.e., medial problems are more common with varus knees. Standing allows rating of foot position and pronation as well as limb lengths from iliac crest to the floor. With the patient sitting the angle between the femoral sulcus and the tibial tubercle is observed and the patient swings the knee through range of motion to detect patellar movement (subluxation or “J” sign tracking) and crepitation. The patient then rests in the supine position allowing documentation of any swelling or effusion, range of motion, ligamentous laxity and very importantly a precise mapping of focal/point tenderness. The neurovascular, lymphatic and skin systems are evaluated. Flexibility is for the hamstring with the hip at 90 degrees and the knee maximum extension angle noted. The patient turns to the lateral decubitus position for testing IT band flexibility using the Ober test and then finally ends up in the prone position for evaluation of hip range of motion and measuring the knee maximum flexion angle as a measurement of quadriceps flexibility.

Radiographs
Routine films include standing anterior posterior views, a true lateral and a Merchant patellofemoral view. (Figures 2, 3, 4) If there is any concern for degenerative wear at the tibiofemoral joint a standing flexed (45 degrees in the manner of Rosenberg) posterior anterior view is obtained (Figure 5). If there is clinical concern for varus or valgus malalignment then a long hip to ankle radiograph is obtained to more precisely document alignment (Figure 6).

Magnetic Resonance Imaging
Magnetic resonance imaging is generally reserved for unusual presentations as the history and physical allow the diagnosis of most patellofemoral problems, meniscal tears and arthritis. Avascular necrosis may be apparent of MRI (Figure 7) and not on plane films and current improvements in imaging the articular cartilage are allowing earlier detection of articular cartilage defects with the goal of detection before progression to arthritis.

Bone Scan
Bone scans evaluate the activity of bone and thus may yield a dynamic look at knee homeostasis. The scan may be abnormal with overload (Figure 8), even though other studies are normal. This may aid in directing management to unload this area.

Developing an Approach to Treatment of Knee Cartilage Problems
At this point the differential diagnosis will allow designing a treatment plan. Patellofemoral pain is certainly the most common and is usually best managed by a thorough conservative treatment program, which may included rehabilitation, bracing, cryotherapy and anti-inflammatory medication. The focus this paper, though, is cartilage and thus before planning treatment an overview of cartilage restoration options is appropriate. Cartilage restoration began in response to the inability of the body to repair articular cartilage and the incomplete healing potential of meniscal cartilage. Current research continues to demonstrate that there is a very limited healing response of articular cartilage to injury. Recent research has also shown how vulnerable the articular cartilage is as relatively low energy impacts may cause chondrocyte death leading to gradual deterioration of the extracellular matrix. The final outcome after articular cartilage injury is dependent on both intrinsic and extrinsic factors. When evaluating the long term implications of focal defects, degeneration of the remaining “normal” surrounding cartilage has been historically related to the size and depth of the lesion after controlling for weight, activity and alignment. Clinical studies have suggested that lesions less than one square centimeter usually do not progress and those more than one square centimeter are at risk of progressing. At the 2002 AAOS annual meeting, biomechanical data was presented from different research groups lending basic science support for this clinical observation. These studies showed minimal change in the stress to the cartilage “shoulders” of the remaining normal cartilage surrounding ten-millimeter diameter lesions. Large increases in the stress were demonstrated in the remaining “normal” border tissue when the lesion was greater than twelve millimeters in diameter. Thus, basic science now supports restoring lesion greater that twelve millimeters in diameter and observing smaller lesions.

Basic science continues to demonstrates the superior load bearing and wear characteristics of native hyaline cartilage over all other substitutes. Thus, the goal is to restore all grade III/IV symptomatic articular cartilage defects of diameter greater than ten to twelve millimeters with tissue as close to hyaline as possible using the principles of demand matching. As the size range of these defects is large, additional factors need to be considered when selecting a specific cartilage restoration technique as no single current method duplicates the native hyaline cartilage (even autograft fails to duplicate the articular cartilage originally at the lesion site as, by definition, cartilage is site specific). Factors to be considered: the extent to which the repair/restoration tissue is hyaline-like, total cost, ease of application (for patient and surgeon), difficulty of technique, risks and complications. During the selection process the demand match approach becomes relevant. That is, use the restoration tissue which is a “best fit” for the individual patient and individual knee. With this background, we can further evaluate first articular cartilage and then meniscal cartilage techniques.

The elusive goal of articular cartilage restoration is a straightforward, cost efficient, simple to implement method of initiating hyaline cartilage repair at the time of index evaluation when indicated. Peering into the distant future, the index evaluation may be noninvasive such as an articular cartilage specific contrast agent MRI or PET scan. These studies would then direct a “procedure”, which is tissue specific and initiates a true repair process either through genetic instruction or local growth factor manipulation. The process would create hyaline cartilage to fully repair the defect, reestablish biomechanics and sustain viability over time. Nevertheless, today we are along way from this goal. MRI and PET scans are incomplete tools in the evaluation of cartilage defects, so at present arthroscopy remains the means of inspection to locate, grade, and size the lesion. Cartilage restoration continues to be a work in progress.

Cartilage treatment at the time of index arthroscopy remains controversial and insurance companies applying their own interpretations of what is “medically necessary” further cloud this. Obviously, lesions less than one square centimeter would not be expected to propagate. If a small lesion has mechanically unstable chondrosis which could be creating symptoms or desquamating and causing a synovial response, then a case can be made for stabilization chondroplasty using techniques which cause the least amount of collateral damage (possibly mechanical or water jet). Lesions over one square centimeter discovered at index arthroscopy must be critically approached. What is the probability that the lesion is actually causing the clinical symptoms? What are the potential problems if the lesion progresses in the patient’s expected lifetime? If it is determined treatment of the cartilage lesion is needed, then a cost benefit/demand match analysis is necessary to select the type of treatment. The options available in 2002 are similar to those known over the past 5 years. Repair with fibrocartilage is inexpensive to initiate and requires minimal equipment to breach the subchondral plate. The wear characteristics for fibrocartilage are poor, but may be adequate for small lesions, which have normal contained margins. In those cases the fibrocartilage would be exposed to loads which potentially it could accept, that is typically in the range of 1 to 2 square centimeters. An exciting basic science study suggested in an animal model, that it might be possible to influence the marrow adult stem cells to form hyaline cartilage rather than fibrocartilage. Until this is possible in the human, for larger lesions, it is desirable to have as close to hyaline cartilage as now possible (autologous cultured chondrocytes (Figure 9), or allograft Figure 10)) to be able to accept the higher loads experienced in these larger lesions (greater than 2 square centimeters). Between these lesion sizes, there is the possibility of using autograft osteochondral plugs (Figure 11). Current recommendations suggest close evaluation of harvest site biomechanics and to not exceed 2 square centimeters for autograft transfers. For lesions greater than 2 square centimeters, the current options are typically between ACI and fresh osteochondral shell allograft. The decision to use ACI or allograft is complex and there are overlapping indications. However, the surgeon and patient must be aware of the limited availability of allograft and the potential (low) of infection. The long term success of osteochondral allografts will depend on continued viability of the chondrocytes and their ability to maintain the extracellular matrix homeostais. On the other hand, ACI long term durability depends on the ability of the cells to produce and maintain matrix which closely mimics the properties of hyaline cartilage. With the present state of technical considerations, it appears there may be advantages for the young patient to receive ACI, which may have more reproducible cell viability. For very large lesions, especially those, which are uncontained in the middle-aged patient who could, tolerated conversion to TKA with allograft failure, the option of allograft is attractive. Current fresh allograft techniques using tissue culture techniques will need to demonstrate similar long-term results to those currently in the literature, which have been implanted in less than 48 hours. The advantages of high cell viability in the acute implant must be weighed against the possibility of infection as final culture results typically require approximately 7 days during which time autopsy and social history may also be thoroughly reviewed.

Turning to meniscal restoration techniques, these are in response to the known progressive deterioration of the ipsilateral compartment articular cartilage whenever a meniscal tear is treated with partial or total menisectomy. This deterioration (chondrosis progression) is highly variable in extent and time to onset. The contributions to this variability may include the genetically dictated makeup of the patient’s “baseline” hyaline cartilage, activity, alignment, weight and possibly sex. As a result, with the information available today, “prophylactic treatment” at index surgery with meniscal replacement is not the standard of care. Rather, as no perfect replacement is available at present, only symptomatic post menisectomy patients are candidates for treatment. At the other extreme, earlier clinical experiences showed that meniscal transplantation has a high failure rate in knees with ipsilateral grade III/IV chondrosis. This indicates that there is a delicate balance for timing of meniscal replacement surgery. Close patient follow up in necessary to detect possible onset of chondrosis. The goal is to implement the replacement before advanced chondrosis occurs. Basic science will soon be translated into clinical science as noninvasive monitoring for early articular cartilage damage evolves. Initial use will probably include urinalysis testing for degradation products of hyaline cartilage or enhanced MRI. A clinical tool now available is through web based patient monitoring of pain and function using standard knee scoring tools and a database to detect slight deterioration of knee function which might otherwise escape the patient’s detection (www.KneeScore.com). That said, meniscal transplantation studies at present could only conclude that the patient’s pain in relieved. Long term studies will be necessary to determine the effect on articular cartilage protection or the degree of limiting chondrosis progression. The current accepted standard for meniscal transplantation is a fresh frozen, size matched meniscal allograft fixed rigidly with bone. The bony fixation is an attempt to allow reproduction of hoop stress in the transplant and thus reestablish stress distribution in the compartment. As an alternative to meniscal transplantation, collagen scaffolding remains an interesting approach. Nevertheless, the outcomes must be held to the same standards of meniscal transplantation. That is, reproduction of stress patterns as seen with a native meniscus. Both techniques deserve close monitoring, as intermediate term follow up becomes long term.

Current clinical advances remain incremental. Basic science now is focusing on the use of cell technology and bioreactors to recreate the three-dimensional constructs necessary to address meniscal and articular cartilage defects. Although quite exciting, these advances must always be viewed in the context of the natural history.