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CLEVELAND CL IN IC JOURNAL OF MEDICINE VOLUME 74 • NUMBER 9 SEPTEMBER 2007 663 JAMES ROSNECK, MD Department of Orthopaedic Surgery, Cleveland Clinic Managing knee osteoarthritis before and after arthroplasty REVIEW ■ ABSTRACT Primary care physicians play a key role in the diagnosis and the nonoperative management of knee osteoarthritis (OA), including monitoring for problems in patients who have undergone knee replacement surgery. This article reviews key clinical and radiographic findings of knee OA, options for conservative management, and signs and symptoms of complications after total knee arthroplasty. ■ KEY POINTS Treatments such as unloader braces, high tibial osteotomy, distal varus femoral osteotomy, and unicompartmental knee replacement have a role in the management of end-stage knee OA in certain patients. Knee arthroscopy does not alter the progression of knee OA, and its use is controversial, since trials comparing arthroscopic debridement, lavage, and a placebo procedure reveal no difference among the groups. Improvements in minimally invasive approaches to total knee arthroplasty are yielding excellent outcomes. ODAY THE SURGICAL TREATMENT of osteoarthritis (OA) includes more options than ever. With the aging of the pop- ulation and the increasing demand for OA therapy, surgeons continue to refine proce- dures. Besides the gold-standard total knee arthroplasty (TKA), minimally invasive TKA and computer-assisted techniques are being perfected. Internists play a key role in managing knee OA, from helping patients manage pain early in the disease to referring them for surgery when conservative therapy no longer helps. And even after surgery, primary care physicians help in the follow-up, helping to monitor patients for short-term and long-term complications. This article reviews the key clinical and radiographic findings in OA, options for con- servative treatment, and criteria for surgical referral. While we briefly discuss surgical options, we will also review the signs of com- plications in patients who have undergone knee joint replacement, such as thromboem- bolism, infection, and periprosthetic fracture. ■ KNEE OSTEOARTHITIS: KEY FEATURES Osteoarthritis is a chronic, often widespread form of arthritis that may affect all joint struc- tures and is commonly manifested in the knee. Except for traumatic arthritis, which can occur at any age after an injury, the prevalence of primary (idiopathic) OA increases with age. Its onset is insidious but progressive, resulting in significant pain and disability, often leading to deterioration in function and loss of independence. OA is a disease of aging cartilage. While T *Dr. Barsoum has indicated that he is a consultant to Stryker Orthopaedics and Exactech corporations, has received research support from Stryker Orthopaedics and TissueLink Medical corporation, and has received financial support from Exactech and TissueLink for device or instrument design. VIKTOR KREBS, MD Head, Section of Adult Reconstruction, Department of Orthopaedic Surgery, Cleveland Clinic WAEL K. BARSOUM, MD* Vice-chairman, Department of Orthopaedic Surgery, Cleveland Clinic CARLOS A. HIGUERA, MD Department of Orthopaedic Surgery, Cleveland Clinic NABIL TADROSS, MD Department of General Internal Medicine, Cleveland ClinicCREDIT CME 664 CLEVELAND CL IN IC JOURNAL OF MEDICINE VOLUME 74 • NUMBER 9 SEPTEMBER 2007 its exact pathophysiology is not yet under- stood, OA clearly has many contributors, including a combination of risk factors such as genetics, microtrauma, increased cytokine activity, and obesity. The diagnosis of OA is made both clinical- ly and radiographically. Clinically, the patient with OA has activity-triggered pain that decreases with rest. Other signs and symptoms of OA include knee effusion, crepitation, sub- jective locking and sensation of unsteadiness, angular deformity resulting in gait abnormality secondary to decreased quadriceps strength, and joint inflexibility.1–3 Joint contractures are often seen in severe end-stage OA. The ulti- mate and sometimes devastating result of OA is debilitating pain and loss of independent func- tioning, manifested by the inability to carry out activities of daily living. The clinical manifestations of OA of the knee must be correlated with radiographic findings. The plain radiograph remains the primary objective diagnostic tool. There are four cardinal radiographic findings of OA: • Asymmetric loss of cartilage resulting in joint space narrowing • Subchondral bone cysts • Osteophytosis • Subchondral bone sclerosis. Plain films can also be used to grade the severity of OA. It is now widely accepted that OA has four stages or grades, from 1 to 4 according to severity. Grade 1 is mild OA in which the joint space is preserved, whereas grade 4 is characterized by the loss of articular cartilage with bone-on-bone articulation. At this stage, valgus or varus angular deformity is not uncommon. The clinical severity of OA, based on both radiographic evidence and clinical symp- toms, dictates whether conservative or surgi- cal management is appropriate (FIGURE 1). ■ WIDE RANGE OF CONSERVATIVE TREATMENTS Conservative management should almost always be the first line of treatment for knee OA. It includes physical therapy, exercises for range of motion and strengthening, weight loss, analgesics, intra-articular injections, and orthotic devices. Physical therapy and exercises to maintain range of motion and strength of the affected extremity may improve symptoms. Weight loss also helps by decreasing joint reaction forces in the knee.4 And in patients who eventually require knee replacement, optimal function and range of motion before surgery are important to achieving a successful surgical outcome.5 Overall good health and a lower body mass index also promote a good surgical outcome.5 ■ CURRENT OPTIONS FOR ANALGESIA Nonsteroidals and acetaminophen Acetaminophen and nonsteroidal anti-inflam- matory drugs (NSAIDs) can be used either continuously or as needed. Some of these drugs have well-known gastrointestinal adverse effects, but they remain a staple of early arthri- tis management. Acetaminophen is effective at reducing the pain of arthritis,6,7 but some direct com- parisons with NSAIDs show that NSAIDs are more effective, especially in the long term.8–10 On the other hand, the gastrointestinal, renal, and perhaps cardiovascular side effects of NSAIDs make chronic use inappropriate for certain patients. Avoiding adverse effects Traditional NSAIDs have gastrointestinal adverse effects such as dyspepsia, gastric ulcer- ation, and bleeding due to the inhibition of platelet function. Current recommendations are to include a gastroprotective agent if pre- scribing an NSAID to a higher-risk patient.11 One option is to use one of the selective inhibitors of cyclooxygenase enzyme 2 (COX- 2), which have little effect on COX-1 and consequently fewer gastrointestinal side effects. These drugs also have no significant effect on platelet function, and therefore can be used perioperatively. All NSAIDs may also cause renal side effects, especially in the elderly and in those with preexisting renal insufficiency. The degree of cardiovascular risk from chronic selective or nonselective NSAIDs remains controversial. Tramadol and opioids Other drugs that control pain in knee OA Treatment goals: decrease pain and symptoms and postpone knee surgery KNEE OSTEOARTHRITIS ROSNECK AND COLLEAGUES CLEVELAND CL IN IC JOURNAL OF MEDICINE VOLUME 74 • NUMBER 9 SEPTEMBER 2007 665 FIGURE 1 CCF ©2007Medical Illustrator: Joseph Kanasz ■ Clinical and radiographic features guide management of knee osteoarthritis (OA) In early knee OA, asymmetric loss of cartilage, narrowing of the joint space, and subchondral bone cysts can produce activity-triggered pain that decreases with rest. Other signs can include knee effusion, crepitation, subjective locking and sensation of unsteadiness, gait abnormality, joint inflexibility, and in severe cases, joint contracture. As knee OA worsens, conservative measures are usually tried first, eg, physi- cal therapy, exercises for range of motion and strengthening, weight loss, analgesics (eg, nonsteroidal anti-inflammatory drugs, acetaminophen), intra-articular injections, and orthotic devices. Advanced knee OA often results in val- gus or varus angular deformity, debilitat- ing pain, and loss of independent func- tioning. Referral to an orthopedic surgeon is appropriate. Options include arthroscop- ic treatment, unicompartmental knee arthroplasty, and total knee arthroplasty (TKA). After TKA, complications in the first 90 days include deep vein thrombosis, symptomatic pulmonary embolism, wound infection, pneumonia, and myocardial infarction. Periprosthetic fractures may occur, primarily in the supracondylar area. Any patient who has undergone TKA and who presents with new onset of knee pain after a fall should have a radiographic evalua- tion of the affected joint and, if necessary, surgical reconstruction. Joint space narrowing Subchondral bone cysts Cartilage Osteophytes Total loss of articular cartilage Periprosthetic fracture 666 CLEVELAND CL IN IC JOURNAL OF MEDICINE VOLUME 74 • NUMBER 9 SEPTEMBER 2007 include tramadol (Ultram) and opioid anal- gesics. These are useful during flare-ups if the pain does not respond to NSAIDs or aceta- minophen. Short- and long-acting opioids can be used, preferably in fixed intervals, for less than 2 weeks at a time. Long-term use of opi- oid analgesics is appropriate in patients who are not good candidates for surgery and who have severe pain that does not respond to other drugs.12 ■ TYPES OF INTRA-ARTICULAR INJECTION Intra-articular injections may provide pain relief in knee OA. Multiple combinations of anesthetic and steroid agents have been used successfully and may provide modest relief.13,14 A recent advance is the injection of hyaluronic acid material that provides a substi- tute for normal joint fluid. The goal of these injections is to enhance lubrication, decreasing friction of joint surfaces against one another. A large meta-analysis indicated that hyaluronic acid injections are only slightly more effective than placebo,15 whereas other studies16 show them to be a useful addition to conservative management. Because of these conflicting results, use of these injections remains controversial. ■ WHEN TO TRY ORTHOTIC DEVICES For slight varus or valgus deformity that occurs with unicompartmental degeneration in knee OA, use of an “unloader” brace can reduce the forces that are applied through the diseased compartment of the knee. However, clinical studies supporting the efficacy of unloader bracing are lacking. Other approaches with the same goal include insertion of a medial or lateral heel wedge into the shoe. Lateral heel wedges are used mainly for symptoms related to OA of the medial compartment, while medial wedges may be used to treat symptoms of lateral compart- ment OA.17 If properly fitted, these inserts have shown a reduction in pain over a 2-year period.18 ■ REFERRING THE PATIENT FOR SURGERY If conservative measures fail to control symp- toms and the patient has significant limita- tions to activities of daily living, then referral to an orthopedic surgeon is appropriate. Surgical interventions for knee OA include arthroscopy, osteotomy, patellar resurfacing arthroplasty, unicompartmental knee arthro- plasty, and total knee arthroplasty (TKA). ■ THE ROLE OF ARTHROSCOPY IS STILL CONTROVERSIAL Knee arthroscopy does not alter the progres- sion of knee OA, and its use is controversial, since trials comparing arthroscopic debride- ment, lavage, and a placebo procedure reveal no difference among the groups.19 Yet despite this, it is often used early in the treatment of OA, specifically for mechanical symptoms, and primarily for symptom relief. Carefully selected patients with symptoms that are pri- marily mechanical in nature—eg, presence of loose bodies, locking, or a specific mechanism of injury20—may have some functional improvement after arthroscopy. ■ UNICOMPARTMENTAL KNEE ARTHROPLASTY Unicompartmental knee arthroplasty in which just one femoral condyle is replaced has gained popularity over the last decade because it is less invasive than TKA and has a shorter recovery period. However, very few patients meet the strict selection criteria for this proce- dure. These criteria are as follows: • Degenerative changes must be unicom- partmental, and lack of involvement of the opposite femoral condyle must be confirmed radiographically. • The patellofemoral articulation must have only minimal changes, and both the anterior and posterior cruciate ligament must be intact. • Knee flexion must be greater than 90°, with a flexion contracture of less than 15°. • The patient must have a sedentary lifestyle and weigh less than 275 lbs. Patients with inflammatory arthritis and hemophilia are not candidates for this proce- dure. A recent study following these guidelines revealed a 13-year prosthetic survival of 95%, with good or excellent results attained in 92% of knees 10 years after surgery.21 The KNEE OSTEOARTHRITIS ROSNECK AND COLLEAGUES Grade 4 OA: loss of cartilage with bone-on- bone articulation, and possibly valgus or varus deformity most common reason for eventual conver- sion to TKA was subsequent degeneration in the opposite or patellofemoral compart- ments.21 ■ TOTAL KNEE ARTHROPLASTY If conservative treatments fail or are no longer appropriate, TKA is the best treatment we have for end-stage OA of the knee. Up to 20 years of experience with millions of patients show that TKA improves pain and function. In 1996, more than 607,000 knee and hip replacements were performed in the United States,22 and the number of TKA procedures is expected to increase an additional 85% by 2030.23 TKA continues to be the best option for improving knee pain and function, with the ability to correct varus or valgus articular deformity in end-stage OA. It is the treatment of choice in patients over age 55 with progres- sive and painful OA in whom nonsurgical and less-invasive treatments have failed. The increasing demand for TKA has placed high emphasis on improvements in technique, instrumentation, and operating room efficiency. Such changes have improved patient outcomes and decreased the complica- tion rate. The goals of TKA TKA creates a kinematically stable, solidly fixed, and well-functioning knee, and success depends on good fixation techniques, soft-tis- sue balancing, and restoration of the mechan- ical axis. Lack of attention to any of these could lead to an imperfectly reconstructed knee that may require surgical revision. Techniques of TKA Although cementless fixation using porous coated pegs and stems has been used, cement- ed component fixation using methylmethacry- late is the most common today. It is debatable whether retention, sacrifice, or substitution of the posterior cruciate ligament leads to better outcomes with primary TKA.24 The senior authors of this article (V.K., W.K.B.) retain the posterior cruciate ligament in most cases if it is intact at the time of surgery. Some feel that cementless implants are advantageous for young patients, but there is no clinical evidence of improved implant sur- vival or function of cementless prosthetics. ■ MANAGING THE COMPLICATIONS OF TKA While the rate of complications after TKA is low, complications that occur can be devas- tating or even lethal. The most common complications within 90 days of TKA include symptomatic deep vein thrombosis (2.1%), pulmonary embolism (0.8%), wound infection (0.4%), pneumonia (1.4%), myocardial infarction (0.8%), and death (0.7%).25 Deep vein thrombosis Deep vein thrombosis is the most common complication after TKA and is thought to be multifactorial. Risk factors include age older than 40, prolonged immobilization, anesthe- sia and a surgical procedure involving the lower extremities, a history of cancer, a histo- ry of deep vein thrombosis, and obesity. Associated hemostatic abnormalities include antithrombin III deficiency, protein C or S deficiency, history of heparin-induced throm- bocytopenia, dysfibrinogenemia, myeloprolif- erative disorder, or the presence of lupus anti- coagulant.26 Protocols for routine screening for throm- boembolism after total joint replacement are controversial and vary across the United States. The protocol followed by the senior authors of this article (V.K., W.K.B.) includes duplex ultrasonography on postoperative day 2. Any detected thrombosis is treated with full anticoagulation, regardless of the symptoms. Fatal pulmonary embolism occurs in less than 0.5% of all cases of TKA,27 and in less than 0.1% when prophylaxis is used.28 However, as pulmonary embolism is considered to be in a continuum with deep vein thrombosis, it is treated with full anticoagulation as necessary. The literature is filled with evidence to support the effectiveness of thromboprophy- laxis in reducing the incidence of deep vein thrombosis and fatal pulmonary embolism.29 Although controversy still exists over which agents are best at preventing and treating thromboembolism, the prevalence of throm- bosis after treatment ranges from 35% to 50% CLEVELAND CL IN IC JOURNAL OF MEDICINE VOLUME 74 • NUMBER 9 SEPTEMBER 2007 667 Hyaluronic acid joint injections: sometimes useful, but still controversial KNEE OSTEOARTHRITIS ROSNECK AND COLLEAGUES 668 CLEVELAND CL IN IC JOURNAL OF MEDICINE VOLUME 74 • NUMBER 9 SEPTEMBER 2007 after TKA without prophylaxis.30 Recommended prophylaxis. Thrombo- prophylaxis can be mechanical or pharmaco- logic. The predominant mechanical approach involves an external pneumatic compression device, which increases venous return, decreases stasis, and enhances fibrinolysis.31 Mechanical devices used alone have not proven to be more effective than pharmaco- logic prophylaxis alone; therefore, it is felt that a combination of the two gives the best protection.31 Drugs currently used for thromboprophy- laxis include aspirin, warfarin (Coumadin), low-molecular-weight heparin (LMWH), and fondaparinux (Arixtra). Current thrombopro- phylaxis after TKA is based on the 2004 guidelines of the American College of Chest Physicians,32 which recommended prophylax- is for 7 to 14 days after surgery. The drugs to use are LMWH (30 mg every 12 hours), war- farin (international normalized ratio of 2.0 to 3.0), or fondaparinux 2.5 mg daily.32 The guidelines do not recommend aspirin,32 for several reasons: studies are few and method- ologically flawed; a number of trials either found aspirin to be of no significant benefit or found it to be inferior; and aspirin is associat- ed with a risk of bleeding. However, some authors report using aspirin for thrombopro- phylaxis in their TKA patients, with a rate of fatal pulmonary embolism of less than 0.1%.28 The risk of perioperative bleeding increases 1.8% to 5.2% with LMWH or warfarin, and this effect is dose-dependent.28 Enoxaparin (Lovenox) is a highly effec- tive thromboprophylactic agent, but its wide- spread use is limited by a documented increased incidence of bleeding complica- tions.33 The newest drug for thromboprophylaxis is fondaparinux, a synthetic and specific inhibitor of activated factor X (Xa). Its long half-life allows for once-a-day administration; however, its effectiveness and risk profile are still being studied. Pain The goal of joint replacement surgery is to restore an appropriate, pain-free level of func- tion. However, some patients have pain after TKA. When determining the cause of the joint pain in a patient who has undergone TKA, the physician should consider whether the pain has been present since surgery, or if it developed after an initial pain-free interval, and if th