Management of Osteoarthritis Pain

                                                 Dr. KS Dhillon

What is osteoarthritis

Osteoarthritis (OA) is the outcome of a range of disorders that result in structural and functional failure of synovial joints where the dynamic equilibrium between the breakdown and repair of joint tissues is overwhelmed [1].

Abnormal mechanical stresses on healthy cartilage can lead to structural failure of articular cartilage.  It can also result from pathologically impaired cartilage degenerating under the influence of normal physiological strains [1]. Although two subsets of OA are described, i.e primary and secondary OA, in the majority of cases the pathogenesis is multifactorial, involving environmental and genetic factors. Occupational factors, trauma, body weight, recreational activities, developmental abnormalities, denervation of joints, collagen gene mutations, and inherited as well as acquired errors of metabolism play a role in the pathogenesis of OA.

Osteoarthritis may cause pain, physical disability, as well as psychological distress [2]. There are many individuals who have structural changes in the joint which are consistent with OA but are asymptomatic.

The proportion of individuals with radiographic OA of the knee who have knee pain can range from 15% to 81% and those with knee pain who have radiographic osteoarthritis ranges from 15-76% [3]. The reasons for this discordance between radiographic changes and knee pain in patients with OA remains ill-defined.

Symptomatic OA of the knee with pain on most days and radiographic features consistent with OA is present in about 12% of individuals aged 55 years and above [4].

OA is more prevalent in the hand as compared to the knee. OA of the base of the thumb when symptomatic can cause substantial pain, instability, deformity, and loss of motion leading to functional impairment [5]. About 5% of women and 3% of men after the age of 70 have symptomatic OA of the thumb with impairment of hand function [6].

The hip OA prevalence is about 9% in Caucasian populations [7] and the prevalence is very low in Asian, black, and East Indian populations. This indicates that the prevalence of hip OA is very low [8]. The prevalence of symptomatic OA of the hip OA is about 4% [9].

Symptoms and signs of OA

Pain is the predominant symptom in patients with OA. The onset of pain is usually insidious. It is often deep-seated, not localized, and activity-related or mechanical. In the advanced stage of the disease, the pain may occur at rest and at night [10].

Other symptoms include stiffness, joint instability, buckling or giving way, reduced function, swelling, crepitus, and loss of motion in the joint.

Some of the signs of OA include joint tenderness, crepitus, bony enlargement, reduced range of joint motion, pain on passive joint motion, deformity, instability of the joint, swelling of joint, muscle wasting, and altered gait [10]. 

Diagnosis of OA

The diagnosis of OA is made on the basis of the history and physical examination. X-rays are done to confirm the clinical suspicion and to rule out other conditions. No laboratory tests are needed for the diagnosis of OA.

The radiographic features commonly used to define OA include osteophytes, joint space narrowing, subchondral sclerosis, cyst formation, and bony contour abnormalities (e.g. femoral head). The most widely used grading system is the one introduced by Kellgren and Lawrence [11]. The grading system has 4 grades of OA based on radiological examination;

Grade 0: No OA; when there are no features of OA.

Grade 1: Doubtful OA; when there are minimal osteophytes of doubtful

               significance.                                                                                 

Grade 2: Minimal OA; when there are definite osteophytes but the joint  

               Is normal.

Grade 3:  Moderate OA; when there is moderate decrease in joint space

Grade 4:  Severe OA; when joint space is markedly reduced with 

                subchondral sclerosis.

                   

Treatment of OA

There are pharmacological, non-pharmacological, and surgical approaches to the treatment of OA. Treatment is essentially symptomatic. Patient education is at the core of the management of patients with symptomatic OA. Presently, there are no effective disease-modifying drugs available nor is a cure in sight. There is a widely held view, though erroneously, that OA is inevitably a progressive disease. Studies have shown that 12 to 17% of patients can show improvement over the years, 22.5 to 27% can remain the same, and 56 to 64% can get worse [12,13]. However radiographic changes, symptoms, and function must be seen as independent outcome measures since they do not always correlate.

Non-Pharmacological Treatment

Exercise

All guidelines on the treatment of OA recommend exercise for the treatment of OA, especially for the knee. It has not been established which is the best form of exercise but aerobic and strengthening exercises have shown modest effects on pain relief. Exercises for patients with OA have to be individualized and patient-centric. It is most likely to be sustained if it is part of the patient’s daily routine or when it is done in groups. There is no evidence that exercises will accelerate the OA provided injury is prevented [14].

Weight loss

All guidelines advocate weight loss for those patients who are overweight. Studies have shown that obesity is a risk factor for developing OA, as well as a risk factor for progression of OA. Random controlled trials (RCTs) have also shown that weight loss reduces pain and improves function in patients with knee OA.  A 5% weight reduction for those who are overweight is recommended for significant benefit. Calorie reduction should go hand in hand with exercise. However, there is no evidence that weight reduction will slow the progression of OA and there is also no evidence that it will benefit patients with hip OA [14].

Footwear and orthotics

Most RCTs show that there is no benefit of footwear and orthotics in the management of OA of the knee and there are no studies for hip OA. There have been two studies espousing the benefits of lateral and medial insoles for knee OA. However, most believe that the symptomatic pain relief may be due to a placebo response. If the orthotic is not too expensive it may be offered as an adjunct to other therapy [14].

Knee braces, patellar bracing and walking aids

There is no firm evidence that these devices are beneficial in the treatment of OA. At best there is weak evidence of some benefit of these modalities of treatment. They could be used as an adjunct in the treatment with other forms of treatment [14].

Transcutaneous electrical stimulation (TENS) 

TENS is not recommended in patients with knee and/or hip OA. The studies examining the use of TENS have been of low quality with small size and variable controls. This makes comparisons across trials difficult. Generally, studies have demonstrated a lack of benefit for patients with knee OA.

Pharmacological Treatment

Simple analgesics and paracetamol

All guidelines recommend paracetamol or its equivalent for the treatment of OA. Its efficacy has been well established for knee OA but there is less evidence for its efficacy for OA of other sites. Though it is less effective as compared to nonsteroidal anti-inflammatories (NSAIDs) for symptomatic relief, the cost and lesser side effects gives it an edge over NSAIDs. However, the lack of knowledge and belief in its efficacy among professionals and patients need to be overcome [14].

Topical NSAIDs and Capsaicin

Although some studies have shown the effectiveness of topical NSAIDs and Capsaicin for short-term use in the treatment of OA, many believe that there is a considerable chance of a placebo effect as well as publication bias. There is weak (Grade D) evidence for use of such treatment modalities in OA of the knee. These modalities can be used as an adjunct for short term treatment [14].

NSAIDs and COXIBS

There is a large body of evidence on the effectiveness of NSAIDs and Coxibs in the treatment of symptoms of OA. However, their effectiveness is small and is of short duration. These drugs due to their potential side effects should be used for the shortest duration whenever possible. NICE (National Institute for Health and Clinical Excellence, UK) having conducted some cost-effectiveness studies has recommended the use of these drugs with proton pump inhibitors (PPIs) when indicated. According to NICE guidelines, Celebrex is the most cost-effective of these drugs in the UK. For patients with gastrointestinal and cardiovascular risks, NSAIDs were not a cost effective alternative to paracetamol, with risk outweighing the benefits. The guidelines also recommend that patients with OA who are on Aspirin should consider other alternatives before using this class of drugs. All patients should be informed of the possible side effects of the use of these drugs. Despite evidence that paracetamol may be inferior to NSAIDs for pain relief in OA, the risk-harm trade-off and the cost places paracetamol ahead of NSAIDs [14].

Opioids

Evidence for use of opioids in the treatment of arthritis is weak. Their use is recommended for moderate to severe OA. The benefits for pain are moderate and for function small. Their usefulness is limited by their well-known side effects. There is a lack of long-term data on the efficacy and safety of their use in OA [14].

Glucosamine and Chondroitin

The AAOS (American Academy of Orthopaedic Surgery) clinical practice guidelines (18th May 2013) [15] does not recommend the use of glucosamine and chondroitin for patients with symptomatic OA of the knee and the strength of their recommendation is strong. Despite the availability of extensive literature on the subject, there is no evidence that clinically important outcome has been achieved compared to placebo.

Hyaluronic Acid

The AAOS guidelines also strongly recommend against the use of hyaluronic acid for the treatment of patients with symptomatic osteoarthritis of the knee. This recommendation is based on the lack of efficacy of intra-articular hyaluronic.

Intra-articular Corticosteroids

The evidence for the use of intra-articular corticosteroids in the treatment of knee OA is inconclusive. There is a need for the use of clinical judgment for use of intra-articular corticosteroids. Patients with persistent synovitis of the knee may benefit.

NGF monoclonal antibody tanezumab

Nerve growth factor (NGF) is known to be involved in pain signaling and has been implicated in causing pain in patients with OA. In the early clinical trials of the NGF monoclonal antibody tanezumab, investigations involved the use of intravenous tanezumab where the doses were body weight-adjusted or administered as a fixed-dose (up to 10 mg). 

In some of these patients, rapid progression of osteoarthritis (RPOA) was observed. Histomorphological changes in the sympathetic nervous system were also observed in preclinical animal studies. In subsequent studies, comprehensive monitoring of joint and neurological safety was implemented.

Further trials were conducted where lower doses of tanezumab were administered subcutaneously in difficult-to-treat patients. Extensive risk mitigation and surveillance, excluded patients with evidence of or risk factors for RPOA. 

Subcutaneous tanezumab at a dose of 5mg given every 8 weeks significantly improves pain, physical function, and patient’s global assessment of OA (PGA-OA) at 24 weeks in patients with moderate-to-severe OA who have failed to respond or could not tolerate standard analgesics. 

About 1.4% of the patients receiving 2.5 mg tanezumab develop RPOA and 2.8% of patients receiving tanezumab develop RPOA.

Surgical Treatment

Arthroscopy, partial meniscectomy, and debridement of the Knee

The AAOS guidelines strongly recommend against the use of arthroscopy with lavage and/or debridement of the knee in patients with OA. Randomized control trials have shown no benefits of such a procedure as compared to physical therapy and medical treatment [16,17]. This recommendation does not apply to patients with a primary diagnosis of mechanical derangement of the knee who have concomitant OA of the knee. There is level I evidence that partial meniscectomy in patients with OA of the knee provides no benefit to the patients and that there is no scientific basis for continuing such a practice [18].

 

Osteotomies around the Knee

The AAOS guidelines recommend that a practitioner may do a valgus high tibial osteotomy for symptomatic medial compartment OA of the knee. However, the strength of the recommendation for this procedure is limited because the quality of supporting evidence is unconvincing. Low-strength case series have shown decreased pain on VAS after high tibial osteotomies. For distal femoral varus osteotomies, evaluation for the recommendation was not done due to a lack of appropriate studies.

Joint Replacement Surgery

Joint replacement surgery is a well-known effective and cost-effective intervention for the treatment of OA of the hip and the knee joints. Owing to its irreversible nature and its limited lifespan, it is usually reserved for patients with severe disabling OA which is not amenable to other forms of surgical or conservative treatment. The decision as to when in the course of the disease a joint replacement should be done has not been resolved. The indications for joint replacement remain unclear. After knee replacement, 10-20% of people are unhappy with the outcome [19]. Besides surgical technique and implant factors, much of the cause of pain and disability remains unexplained. Though socio-demographic factors such as older age, female gender, and low socioeconomic status have been associated with poorer outcomes, physiological aspects do play an important role, possibly related to central sensitization (the dysfunction of pain modulation in the CNS) [20].

The long term survival of prosthesis in total joint arthroplasty of the hip and knee has been extensively studied. More than ninety percent of hip prostheses do not need revision at 10 years and 80% of the total knee prostheses do not need revision at 15 years. However, the quality of life (QOL) SF-36 scores for patients with joint arthroplasty are not as encouraging. Rat et al, in a study of 3 and 10 years follow up of a patient cohort with hip and knee arthroplasty, showed that at 3 years the QOL scores remained limited as compared to age-matched general population and at 10 years the scores were lower than the reference population [21]. 

The risk factors for the requirement of joint replacement in patients with osteoarthritis have not been fully elucidated. However, a dose-response association between body mass index and subsequent need for hip and knee replacement has been established. A higher body mass index and obesity significantly contributes to the overall risk of undergoing a hip or knee replacement [22,23]. Total physical activity level was found to have a dose-response relationship to risk of primary knee replacement but not to hip replacement [24]. The Ontario Joint Replacement Registry 2004 report showed that 84% of patients receiving knee replacement were overweight or obese with a BMI of more than 25 [25].

It is often erroneously believed that a large proportion of patients with post-traumatic OA will need a joint replacement of the hip or the knee. An analysis of the patients who had a knee replacement in Canada, by the National Canadian Joint Replacement Registry in 2004, showed that the primary diagnosis for a total knee replacement was degenerative OA in 93%, inflammatory arthritis in 5%, post-traumatic OA in 2%, and avascular necrosis in 1% of the patients [25]. Post-traumatic OA constitutes 12% of the global burden of OA but only 2% of the total knee replacements done are for post-traumatic OA. Hence, primary degenerative OA is a bigger risk factor for a knee replacement than post-traumatic OA. 

Rademakers et al in an analysis of 109 patients with surgically treated fractures of the tibial plateau with an average follow-up of 14 years showed a 5% incidence of secondary OA of the knee which required reconstructive surgery (knee replacement, arthrodesis, or osteotomy) [26]. Mehin et al in a study involving 286 patients with tibial plateau fractures followed up for 10 years, found a 3% incidence of end-stage OA requiring reconstructive surgery [27]. Two percent of the 286 patients had a knee replacement.

Ankle joint replacement has been touted as a viable option for the treatment of end-stage ankle arthritis. However, some early reports showed failure rates as high as 72% [28]. More recent studies have reported an 89% survivorship at 10 years but the quality of evidence in support of ankle replacement is weak and fraught with bias. High quality randomized control trials comparing ankle replacements with other forms of treatment for ankle arthritis are lacking [29].

Arthrodesis of Joints

Arthrodesis of major weight-bearing joints of the lower limb such as the hip and knee was widely used for end-stage arthritis before the advent of successful joint replacement arthroplasty. Presently it is widely used for end-stage arthritis of the ankle and not for the hip and the knee where the results of hip and knee replacement are excellent. Arthrodesis provides excellent permanent pain relief but at the expense of loss of motion of the joint. Furthermore, it can cause excessive stresses on adjoining joints leading to degeneration of these joints. Hip and knee arthrodesis is still a viable option in a selected group of patients. Limited lifespan of joint arthroplasty dictates that patients who are expected to live more than 30 years may be candidates for arthrodesis of the hip or knee for end-stage arthritis of the hip and knee joint. This is especially true for those patients who are involved in heavy manual labor.

Coester et al in a study of 23 patients with ankle arthrodesis for isolated post-traumatic OA of the ankle, followed up for a mean of 22 years found that there was accelerated degeneration of the subtalar, calcaneocuboid, naviculocuneiform, tarsometatarsal, and the first metatarsophalangeal joints of the same foot as compared to the opposite foot. However, the knee joint was spared of degenerative changes in all the patients [30].

Schafroth et al [31] in a retrospective study of 30 patients with an arthrodesis of the hip at an average follow up of 18.2 years found that the VAS (visual analogue scale) for pain in the fused hip was an average of 1.9 (0-8), the contralateral hip 2, ipsilateral knee 2.0, contralateral knee 1.8 and low back 3.6. The average walking distance was 111 minutes (range 10 to unlimited). The average SMFA (short musculoskeletal function assessment) was 31.2 (range 9-70). They concluded that if the arthrodesis is done with optimal alignment of the limb then complaints from adjoining joints are minimal even in the long term and an acceptable quality of life is possible. Seven of the hips were eventually successfully converted to a total hip arthroplasty [31].

There is a dearth of literature on the long term outcome of arthrodesis of the knee, which is partly due to the success of knee replacement since the 1970s. Presently arthrodesis is done mainly for failed joint replacements, sepsis, Charcot joint, flail knee, tumors around the knee, and end-stage post-traumatic arthritis in young individuals who are not suitable for a knee replacement. An arthrodesis of the knee can provide a stable and painless limb especially in patients in whom a lot of walking is required for their daily activities. An arthrodesis from a functional perspective will always be superior to an above-knee amputation.

Conclusion

There is a widely held view, though erroneously, that OA is inevitably a progressive disease. Studies show that 12 to 17% of patients can show improvement over the years, 22.5 to 27% remain the same, while 56 to 64% can get worse. Radiographic changes, symptoms, and function are independent outcomes and do not correlate.

Contrary to a commonly held view, studies reveal that there is no evidence that glucosamine, chondroitin, and hyaluronic acid have any clinical outcome benefits in the management of OA of the knee. There is strong clinical evidence (RCTs) that arthroscopic lavage, partial meniscectomy, and /or debridement of the knee for OA is of no benefit to the patient.

It is often quite erroneously believed that a large proportion of patients with post-traumatic OA will require a joint replacement, however, demographics of patients undergoing knee replacement for OA show that in 93% of patients the diagnosis was degenerative OA, 5% inflammatory arthritis, 2% posttraumatic arthritis and in 1% avascular necrosis. Post-traumatic OA forms 12% of the global burden of OA but only 2% of patients undergoing knee replacement have post-traumatic OA. In surgically treated fractures of the tibial plateau, the incidence of post-traumatic OA requiring reconstructive (knee replacement, arthrodesis, or osteotomy) surgery was only 5%. Hence a large proportion of patients do not develop end-stage post-traumatic OA which would require reconstructive surgery.

Now to answer the questions posed by the retired member of the judiciary that was raised earlier. In light of present knowledge, there is sufficient evidence to express in percentages the likelihood of a person developing OA, though it cannot be expressed in absolute numbers. It would vary with the joint involved and the severity of the trauma. The degenerative process probably starts immediately at the time of injury and clinical manifestation occurs when the reparative process is overwhelmed by the degenerative process. The latent period may vary from a year to more than 20 years. We however need to remember that not all patients after an injury will develop OA. Age is a very important factor in both the risk for developing OA as well as for progression of the OA. Older age is a risk factor for both. Finally, the likelihood of developing OA and the chance of needing future surgery is very much dependent on the joint involved. 

Research in recent years has debunked many of the long-held pervasive dogmatic myths perpetuated by intuitive and unsystematic clinical experience.

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