We have written an eBook on knee arthritis and operations for cartilage repair which provides greater detail if you would like more information. Find this eBook and more at noyeskneebookseries.com
Operations for Knee Arthritis: What To Do When All Else Has Failed To Stop Your Knee Pain
- Understanding osteoarthritis and post-traumatic arthritis
- Operations for cartilage repair, restoration, transplantation
- Operations for lower limb realignment
- Partial and total knee replacement
- Home exercises
Surgical Advances in Articular Cartilage
A Common Problem
Damage to the articular cartilage of the knee through injury (post-traumatic arthritis) or “wear and tear” (osteoarthritis) is one of the most common yet difficult problems seen by orthopedists today. The gradual deterioration of the knee joint, typically known as osteoarthritis, affects millions of individuals each year. If you suffer from this problem and are over the age of 60, a total knee replacement provides dramatic and reliable relief from pain and is the best treatment. However, if you are younger, total knee replacement is not the best option. Before deciding the proper treatment, we have to thoroughly understand what is exactly injured and wrong with your knee.
There are many causes of arthritis and treatment depends on a multitude of factors, including the condition of your ligaments, menisci, articular cartilage, and the alignment of your leg. Research has shown that the success rate of cartilage procedures depends on the knee being stable and in correct alignment. Therefore, in many knees, cartilage regeneration or restoration procedures are done along with other procedures (such as an osteotomy or ligament reconstruction) to try to correct all of the problems present.
What is Cartilage?
Actually the word cartilage is a general term that describes different structures of the knee. While the composition of these structures is similar, they have different functions or jobs in the knee:
The meniscus acts as a cushion and stabilizing platform between the femur (thigh bone) and tibia (shin bone). There are two menisci in the knee – a medial (or inside) meniscus and a lateral (or outside) meniscus. The menisci are commonly damaged through twisting injuries. Fortunately, some meniscal tears heal on their own and never require surgery. However, at least one-half of injured menisci do not heal and cause pain, locking, and catching. Many surgeons will remove the damaged sections of the menisci to relieve these symptoms. If too much tissue is removed, the meniscus loses its ability to act as the cushion between the femur and tibia, and damage to the articular cartilage begins.
The articular cartilage, also known as the joint lining, is a protective layer of tissue located on the ends of the bones that come together in the knee joint. These bones are the femur (thigh bone), tibia (shin bone), and patella (kneecap). An arthroscopic photograph of a knee with normal articular cartilage and meniscus is shown below:
Articular cartilage may be damaged through an injury or gradually deteriorate over time from a variety of factors. When the articular cartilage is damaged or injured, it usually goes through a staged process of softening, flaking, fragmenting, and finally complete loss where the underlying subchondral bone is exposed. An arthroscopic photograph of a knee with severe damage to the articular cartilage, and no meniscus tissue left, is shown below:
This process is commonly known as osteoarthritis. Damaged or injured articular cartilage has a very limited ability to heal itself. Therefore, once the process of osteoarthritis starts, there is little that the body can do to stop the deterioration.
The stages of deterioration to articular cartilage are shown below. We use a classification system to grade cartilage damage. The grade assigned depends on the size and depth of the lesion. As you can see, the worst is Grade 3B, which all of the articular cartilage has worn away and the underlying subchondral bone may also be eroded.
To complicate matters even further, some knees have additional problems because the entire leg is out of alignment or the leg is unstable due to an injury to a knee ligament. The loss of a meniscus can sometimes cause the leg to bow and lose its normal alignment. In other cases, patients are born with bowed legs and over the years, the pressure on one side of the knee causes damage to the meniscus and articular cartilage. Some knees that have suffered injury to the anterior cruciate ligament have many giving-way reinjuries that produce damage to the menisci and articular cartilage. At Cincinnati Sportsmedicine, knees with these complex problems are seen all too frequently on a weekly basis.
What Can Be Done?
The good news is that important advances in medical knowledge and surgery now provide several options to patients with these problems. Tears to the menisci can often be repaired with an 80-98% success rate, depending on exactly where the meniscus is torn. An arthroscopic photograph of a repaired meniscus tear is shown below:
We can also transplant new menisci into the knee from donors. It is important to perform these transplants before too much damage has occurred to the articular cartilage. A transplanted meniscus is shown in the artist’s illustration below:
Leg alignment problems can be corrected through osteotomy which is a highly successful technique to relieve pressure on the inside (medial) portion of the knee. And, our success rate for arthroscopic-assisted anterior cruciate ligament reconstruction of 94% is one of the highest reported in the country. Patients with these complex problems must realize that all of the problems in the knee must be corrected in order for cartilage restoration procedures to be effective.
Articular Cartilage Restoration Procedures
There are several procedures that can be done for damaged articular cartilage. The decision of which procedure to perform is based on the extent of damage seen during arthroscopy and on MRI scans and x-rays. Important indications include the size of the damaged area, the condition of the cartilage that surrounds the lesion, the amount of space that exists between the femur and tibia, and the condition of other structures in the knee joint.
Small articular cartilage lesions (less than 1 cm2 in diameter and extending only partially down into the cartilage; not to the subchondral bone which lies beneath the articular cartilage) are usually treated arthroscopically by debridement and drilling, abrasion, or microfracture. The drilling/abrasion/microfracture procedures all work off of the concept that producing very small holes in the subchondral bone will stimulate a healing response that forms tissue resembling articular cartilage (called fibrocartilage). Clinical research studies have reported mixed reviews of the results of these procedures, and further investigation is needed on the ability of fibrocartilage to reduce pain and restore function over the long-term.
Larger articular cartilage lesions present difficult problems and only a few surgeons are experienced with the newest procedures designed to restore normal articular cartilage surfaces. For younger patients, several of these procedures are under close study at our Center.
Osteochondral Autograft Transfer Procedure
This operation is used for painful articular cartilage lesions that are approximately 1-3 cm2 in diameter (although size is not an absolute indicator) and extend down to subchondral bone. Such lesions that are surrounded by normal appearing cartilage are well suited for this operation. The defects may be located on either the femoral condyle, the undersurface of the patella, or the femoral sulcus. Larger, deeper lesions do not do as well with this operation because of the technical limitations of the procedure.
The operation is indicated for younger, active patients under the age of 50 who have a normal or nearly normal amount of joint space on x-rays. The repair tissue typically consists of approximately 89-90% hyaline (articular) cartilage and 10-20% fibrocartilage. The durability of the repair tissue over a long period of time (15-20 years) has not been established. To date, we have performed this operation in 130 patients.
This operation is done with the use of an arthroscope and a small incision. Any loose or fragmented pieces of cartilage are removed from the knee. The area of cartilage damage is measured to make sure the osteochondral autograft transfer procedure is indicated. Then, small cylinder plugs of healthy bone and articular cartilage are harvested from the same knee, from the very edges of the femoral condyles or the margin of the intercondylar notch. The plugs that are taken vary in size and number according to the size of the defect to be filled. Drill holes are created within the defect and the plugs are inserted. The goal is to fill as much of the defect as possible (usually, 80-100%) to create a congruent surface.
The largest clinical study reported to date of this operation included 967 patients in Budapest, Hungary who were evaluated over a 10-year period. Clinical scores of knee function showed good or excellent results in 92% of patients who had femoral condylar implants, 87% of those who had tibial implants, and 74% of those who had patellar and/or trochlear implants. A subset of 354 patients (14-49 years of age) who were professional athletes and who were tracked from 2 to 17 years after surgery showed similar results. All but 9% of these patients were able to return to some level of sports activity. The authors recommended the procedure for articular cartilage lesions ranging from 1 to 4 cm2 in size and believed it was superior to microfracture in regard to long-term outcomes.
A study out of Norway reported on 69 patients aged 50 years or less who had this operation and were followed for 5 to 9 years after surgery. The lesions ranged from 1 to 5 cm2 in size and were located in either the medial or lateral femoral condyle in 47 patients, patella in 18 patients, and trochlea in 4 patients. The authors reported that 23 patients required another operation 1 to 5 years postoperatively for unresolved knee pain. Still, improvements were noted with knee function with daily activities in 77% of the patients and 88% indicated they would have the same operation again.
A group from Italy followed 30 patients aged 17-46 years who had femoral condylar defects treated with this procedure for at least 7 years after surgery. The lesions treated were small, ranging between 1.0 to 2.5 cm2. Twenty-four patients were athletes, of whom 9 also required an anterior cruciate ligament reconstruction. The knee condition at follow-up was rated as normal or nearly normal in 77% and 21 were able to participate in sports, although most at a lower level. Three experienced a failure of the operation and required further surgery. MRI studies showed complete integration of the “plugs” in 75% of the cases.
Studies performed in the U.S. have also been conducted and reported acceptable results in the short-term (4 years after surgery) in patients with smaller lesions (1.0 to 2.5 cm2) located on the femoral condyles. One study from New York followed a small series of 22 patients who had patellar lesions treated with this operation an average of 2 years after surgery. The clinical results were positive, with all patients except one showing improvement in knee function scores. MRI showed complete or nearly complete fill in all plugs, with 71% being completely incorporated and flush with the adjacent cartilage.
The results of the osteochondral autograft transfer procedure have been compared to those of microfracture. A study from Lithuania followed 57 athletes (mean age, 24 years) who had either the osteochondral autograft transfer (28 patients) or microfracture (29 patients) for 3 years postoperatively. Clinical scores of knee function showed that 96% of the osteochondral autograft transfer patients had excellent to good results compared with only 52% of the microfracture group. In addition, 93% of the osteochondral autograft transfer patients returned to sports activities compared to 52% of the microfracture group.
The advantages of osteochondral autograft transfer include transfer of healthy hyaline cartilage from the patient’s own knee, ability to perform the operation in a single operation (compared to autologous chondrocyte implantation, discussed next), no additional fixation required (such as medical grade screws, wires, or glue), and ability to combine this operation with other procedures such as knee ligament reconstruction, osteotomy, or patellar realignment.
The disadvantages are limited donor area, potential “dead” space (no living cells) between the plugs resulting in the formation of fibrocartilage, and the potential for plug incongruity on the cartilage surface. In our experience, smaller isolated lesions on the femoral condyles fair best with this operation.
Autologous Chondrocyte Implantation (ACI), First Generation
Autologous chondrocyte implantation (ACI) was developed in the late 1980’s-early 1990’s to treat medium to large areas of articular cartilage damage. This procedure requires two operations. The basic concept is to first take a biopsy from the patient’s knee to obtain normal cartilage cells (chondrocytes). The cells are sent to a laboratory where the chondrocytes are separated from the rest of the tissue, and then multiplied to produce millions of new chondrocytes. Approximately 4-6 weeks later, these chondrocytes are injected back into the patient’s knee. The goal is to regenerate cartilage that more closely resembles normal articular (hyaline) cartilage.
Since the implementation of “first generation” ACI many years ago, “second” and “third” generation variations of this operation have been developed. These include the use of scaffolds and growth factors in attempts to continue to improve the results of this procedure. It is important to know that there are today many surgeons performing first generation ACI, especially in the U.S. where the second and third generation ACI products are not available.
In the United States, only one company (Genzyme) has approval from the Food and Drug Administration (FDA) to provide the laboratory services of culturing and growing chondrocytes. The cell therapy product is called Carticel and has been available since 1997. We were involved in the initial development of the research protocol for the clinical studies Genzyme conducted on this product, which continue today. We have performed over 50 of these operations to date for articular cartilage lesions in both the tibiofemoral and patellofemoral compartments.
Patient candidates are under the age of 50 (must be skeletally mature) with a grade 2B or 3A articular cartilage lesion. There must be a normal or nearly normal amount of joint space in the knee between the femur and tibia and between the femur and patella. The cartilage lesion must be surrounded by normal or nearly normal articular cartilage. It is possible to treat more than one lesion in the knee at the same time. The patient must have normal lower extremity alignment, patellar tracking, and functioning knee ligaments. If there are any problems with these factors, they may be surgically addressed at the time of the ACI. For instance, if a patient has an anterior cruciate ligament tear, it can be reconstructed at the same time as the second ACI operation when the cells are implanted into the knee. ACI is not indicated for patients with widespread osteoarthritis.
Over 30 clinical studies have been published describing the results of first generation ACI. Reports have appeared from the U.S., Germany, Switzerland, Sweden, the United Kingdom, and Australia. Most studies combined patients that had ACI for lesions on the femoral condyle, trochlea, and patellar undersurface into one group. This makes it difficult to reach definitive conclusions of the procedure’s effectiveness according to the location of the lesion. In addition, the size of the lesions varies greatly within and among studies. Defect sizes have ranged from less than 1 to 26 cm2. Patient ages also vary greatly, from 12 to 77 years of age. Patients have been followed from 1 to 18 after surgery. The majority had previous operations for the articular cartilage defect that failed to improve symptoms and knee function.
With these issues in mind, some general conclusions may be reached regarding this procedure. The majority of studies on ACI followed patients for approximately 5 years postoperatively and described successful return to daily activities; few provided data on return to sports activities, especially over a long period of time. Studies that focused on patients with isolated lesions on the femoral condyles reported that, on average, 30% required another surgery (arthroscopy) mostly due to problems with graft hypertrophy (enlargement) or delamination (detachment). At 5 years postoperatively, 3-17% of the operations had failed and the patients required further surgery such as total knee arthroplasty or another ACI. Encouraging findings are that significant improvements were recorded for knee symptoms and function in about 70% of the patients. Studies that have focused on ACI for lesions on the patella and/or femoral sulcus report similar failure and success rates; however, higher percentages (40-50%) of patients with patellar lesions required second arthroscopic procedures due to problems with the ACI graft.
Autologous Chondrocyte Implantation, Second and Third Generation
In an effort to reduce the complication rates and improve the results reported with first generation ACI, other operative techniques have been developed to restore or regenerate damaged articular cartilage. The goals of these newer procedures are to eliminate the need for the periosteal flap cover (thereby reducing the complication rate), perform the procedure with just the use of an arthroscope (eliminating the need for an incision), reduce costs, and improve the quality of the cartilage that grows into the defect. The overall goal is the production of more hyaline cartilage into the defect instead of the traditional mix of hyaline and fibrocartilage that has been reported following first generation ACI operations.
So-called “second” and “third” generation ACI procedures have been described and early clinical studies published. The procedures and products used vary widely and nearly all are currently not available in the U.S. Most of the newer procedures still require two operations; however, there have recently been techniques published that involve just one procedure. The basis of these procedures is tissue engineering and cell therapy in which the expansion or multiplication of the patient’s cells in the laboratory is improved in a manner that will ultimately result in a better quality hyaline cartilage to fill the defect.
In the majority of second and third generation ACI procedures described to date in the medical literature, a biopsy is done in the same manner as described for first generation ACI to extract healthy cartilage. Chondrocytes are extracted from the cartilage and multiplied in the laboratory for typically 4-6 weeks. The processing of these cells varies among laboratories, with some adding proprietary growth factors to enhance cell development.
In second-generation ACI procedures, the chondrocyte cells are injected during the second operation underneath a collagen membrane that serves to cover the defect in place of the periosteal flap. The membrane is usually sutured around the defect in a manner similar as that done in first generation ACI.
Third generation ACI (commonly referred to as matrix induced autologous chondrocyte implantation
Even newer third generation procedures use a tissue-engineered scaffold to deliver the chondrocytes into the knee. The difference in these procedures are that the scaffolds, after being seeded with chondrocytes in the laboratory, are subjected to mechanical stimulation via a bioreactor that applies pressure to the cells for at least 7 days. It is believed that this stimulation will aid in the production of hyaline cartilage. The scaffold is then implanted into the knee and usually secured into the defect with fibrin glue. Scaffolds or matrixes are composed of different materials. Some are composed of injectable gel that is mixed with the cultured chondrocytes.
Even though there have been over 40 clinical studies published on second and third generation ACI, no definitive conclusions can be made on any specific product or procedure. The majority of studies represent case series and have potential conflicts of interest as the companies that produce and sell the product contributed financial assistance to the investigation. Patients have typically only been followed for a few years after surgery, which is too preliminary to assess the durability of these operations. Overall, there does appear to be a decrease in the rate of complications related to graft hypertrophy and delamination compared to first generation ACI. Approximately 80% of the patients reported significant improvement in symptoms and the ability to return to daily activities without problems. Future long-term clinical studies are required to determine the ability of these products and procedures to produce durable, hyaline cartilage that will delay the need for joint replacement long enough to justify the operations.
Single Stage Cartilage Restoration Options
Recently, operative procedures have been described in the literature whose goal is to regenerate hyaline cartilage in a single operation. One procedure uses the DeNovo® NT (Natural Tissue) Graft (ISTO Technologies, Zimmer, USA), which is comprised of allograft articular cartilage obtained from young human donors. The allograft cartilage is harvested and minced by the manufacturer, and then mixed with fibrin glue in the operating room by the surgeon. The allograft tissue is then packed into the articular cartilage defect. This graft is available in the U.S.
Another product currently under FDA Phase III clinical trials in the United States is the DeNovo® ET (Engineered Tissue) Live Chondral Engineered Tissue Graft (ISTO Technologies, Zimmer, USA). This product has “living” allograft tissue consisting of hyaline-like cartilage. Because this tissue is under investigation in the U.S., it is not yet available for general use.
Studies are also underway to determine if the addition of a scaffold to a microfractured defect might improve the quality of the cartilage tissue that is produced by the operation. We previously discussed the main problem with microfracture, which is the production of fibrocartilage or a combination of fibro- and hyaline cartilage. Companies have developed cell-free scaffolds (Chondrotissue®, BioTissue, Germany) and gels (CaReS®-1S, Arthr Kinetics, Austria) that may be used to cover the defect after the microfracture has been completed.
In a similar manner, scaffolds have been created to use following arthroscopic debridement. Some of these contain living cells harvested from the patient’s knee (Cartilage Autograft Implantation System, Depuy Mitek, USA) while others are manufactured and implanted without living cells (MaioRegen®, Fin-Ceramica Faenze Spa, Italy).
“Osteochondral allograft” is an operation in which cartilage is transplanted from a cadaver (donor) to repair a large, full-thickness articular cartilage defect. The transplant contains both articular cartilage and its underlying subchondral bone. It is done in a single operation and is advantageous over the osteochondral autograft transfer operation previously described in that no tissue is taken out of the patient’s own knee and there is no “dead” space (space without living cells) between the small cylinder plugs that exists in the transfer operation. It is very important to correct any other major problems or malalignment in the lower limb, such as knee ligament deficiency, meniscus deficiency, varus or valgus malalignment (bowed legs or knock-knees), or extensor mechanism malalignment (patellar tracking problems). If any of these problems exist, the patient requires a more extensive operation such as a combined osteotomy-osteochondral allograft.
Osteochondral allografts are indicated for large articular cartilage lesions, typically > 3 cm in diameter and > 1 cm in depth. They offer a good option for patients who have developed these lesions due to osteochondritis dissecans or avascular necrosis. Large lesions from fractures to the patella or tibial plateau may also be treated with this operation. Finally, knees in which other articular cartilage restoration or reparative procedures have failed may be considered for this procedure. Patient candidates for this operation are typically young, averaging less than 40 years of age in most clinical studies. The goal in these individuals is to “buy time” until partial or total knee replacement will be required.
Potential problems with the osteochondral allograft operation are limited graft availability, risk of disease transmission or graft rejection, and the technical demands of the operation. This operation is not indicated for patients with widespread arthritis or older patients in whom a partial or total knee replacement offers a better option. Few surgeons have a high amount of experience with osteochondral allografts and the modern literature does not contain as many clinical studies as those that may be found with other articular cartilage restoration procedures. The majority of studies have been conducted in the United States and Toronto, Canada.
An incision is required for this operation, the size of which is determined by the location and size of the lesion. The surgeon inspects the lesion (which would have already been visualized in a prior arthroscopic examination) and palpates it with a probe to determine its exact size and shape. There are two commonly used techniques for osteochondral allografts: the press-fit plug technique and the shell-graft technique.
The press-fit plug technique is similar to that we described earlier for the osteochondral autograft transfer operation. This technique is used for condylar lesions that are 15-35 mm in diameter. Small cylinder grafts are created from the donor knee and, after the lesion has been debrided back to subchondral bone, are press-fit into the lesion.
The shell-allograft technique is a more technically difficult procedure for the surgeon to perform. It is used for larger or deeper defects. The lesion is identified and its dimensions are marked with a surgical pen. A template is made by the surgeon whereby the lesion is drawn on a piece of paper, using measurements obtained at surgery of its width and length and general shape. Then, the donor knee is used to create a graft that matches the size and shape of the lesion. The graft represents a shell that is placed into the lesion (after it has been debrided back to healthy bone). The graft is fixed using bioabsorbable pins or screws.
Overall, the reported results of osteochondral allografts are reasonable. The goals of this procedure are to relieve knee pain and improve function for daily activities in patients who are considered too young for a partial or total knee replacement. Approximately 75% of the operations appear to achieve these goals for at least 10 years. It is important to realize that patients are not typically allowed to resume strenuous sports or occupational activities after this procedure.
Cincinnati Sportsmedicine Opinion
It is evident that controversy continues to surround the field of articular cartilage “repair” and “restoration” and all of the operations that are currently available. Due to the lack of randomized, controlled clinical trials with 10 years or more of patient follow-up, we do not know for certain if one operation is superior to another. The long-term success rates in younger patients remain unknown, especially in regard to return to athletics. We believe there is a lack of scientific evidence to support the return to high-impact loading sports such as soccer or basketball, especially over a long period of time.
The articular cartilage restoration procedures are most likely best suited for isolated lesions on the femoral condyles. It remains questionable if these procedures will produce long-term desirable results for lesions on the patella and tibial plateau, or for multiple lesions. Some patients between 30-50 years of age may benefit more from a unicompartmental (partial) knee replacement. Fortunately, we have decades of experience with all of these operations and are able to assess each patient individually and determine which operation is best indicated for them.