April 2016

The clinical implications of accelerated knee OA

4KneeOA-iStock24183131Accelerated knee osteoarthritis (OA), defined by very rapid radiographic disease progression, is also associated with earlier and more severe symptoms than traditional OA. Identification of these symptoms can facilitate early intervention in this high-risk patient population.

By Jeffrey B. Driban, PhD, ATC, CSCS

Osteoarthritis (OA) is organ failure of a diarthrodial joint, defined as a disease by structural changes (eg, cartilage loss, osteophyte formation, synovitis) and defined as an illness by patient-reported symptoms.1 More than 27 million Americans have OA,2 and this number is rising. Globally, it’s one of the top 15 causes of disability.3,4 Unfortunately, we lack structure-modifying therapies that slow, prevent, or reverse OA progression, and our symptom-modifying therapies are far from optimal.

One challenge of treating individuals with OA is that there are many paths to joint failure, and intervention strategies may need to be tailored to account for specific paths. For example, someone who develops OA after a meniscal injury and someone who develops OA secondary to repetitive overloading from obesity compounded by malalignment may need different intervention strategies to delay or prevent joint failure.

Patients with OA progress at varying rates. For example, individuals with a history of knee injury tend to be diagnosed with knee OA 10 years earlier than those without a history of injury.5 Furthermore, one in four patients who experience an anterior cruciate ligament injury has radiographic OA within five years,6 and two in three patients who suffer a lateral tibial plateau fracture have radiographic OA within nine years.7 More recently, clinical trials8-10 and prospective cohort studies11-15 have helped investigators identify a subset of individuals with accelerated knee OA, in whom the disease progresses even more quickly than post-traumatic knee OA.

Quantifying accelerated knee OA

We recently started studying accelerated knee OA within the OA Initiative, a cohort study primarily of individuals with or at risk for knee OA. The OA Initiative is an ongoing multicenter longitudinal study at four clinical centers in the US: Memorial Hospital of Rhode Island in Pawtucket, The Ohio State University in Columbus, University of Maryland in College Park, Johns Hopkins University in Baltimore, and the University of Pittsburgh in Pennsylvania. The study staff recruited three groups of participants between 2004 and 2006: 1390 individuals with symptomatic knee OA; 3284 individuals without symptomatic knee OA but with risk factors for knee OA; and 122 individuals with no knee OA and no risk factors for OA. Overall, the OA Initiative includes 4796 individuals (58% women) aged between 45 and 79 years (average body mass index = 28.6 ± 4.8 kg/m2).

Clinicians should be concerned about patients without radiographic OA who report knee pain, because it may be an early symptom of accelerated knee OA.

Although the study population is not representative of the US population, it is a valuable cohort because most participants completed annual evaluations. The annual evaluations typically included an array of patient-reported outcomes, physical performance tests, imaging (radiographs and magnetic resonance images [MRI]), and biospecimen collection. All of the data and manuals from the OA Initiative are publicly available for free.16

Figure 1. A conceptual model for the origin of accelerated knee OA.

Figure 1. A conceptual model for the origin of accelerated knee OA.

Within the OA Initiative, 1566 individuals had no radiographic knee OA at baseline and sufficient follow-up data to assess their rate of OA development. We found that 3.4% developed accelerated knee OA, which is defined as having no baseline radiographic knee OA in either knee and developing advanced-stage disease (definite osteophyte and joint space narrowing) within four years.13 Furthermore, 63% experienced this dramatic progression within 12 months.17 Adults who develop accelerated knee OA are typically older, overweight, and more likely to have a history of a recent knee injury than those with a slower onset of knee OA or no knee OA.13,15 Within this subset, our preliminary findings indicated that accelerated knee OA may be related to a history of injuries characterized by subchondral damage, medial meniscal pathology with extrusion (displacement), and lateral meniscal tears; these findings need to be confirmed in larger studies that are underway.14

Assessing symptoms

Although individuals with accelerated knee OA may be characterized by unique risk factors, it’s unclear if their symptoms differ from other adults with a more gradual onset of OA. If adults with accelerated knee OA experience more symptoms and impaired function than those with a gradual onset of knee OA, particularly if symptoms occur earlier in the former, that would underscore the clinical relevance of this subset of people with knee OA and highlight the need to recognize those at risk and intervene if possible to address those symptoms.

We conducted longitudinal analyses among participants in the OA Initiative who had no radiographic knee OA at baseline to determine if accelerated knee OA was associated with greater pain and other clinical outcomes and if outcomes varied over time between those with accelerated knee OA and those with a more gradual onset. We considered participants to have accelerated knee OA if one or more knees developed a definite osteophyte and joint space narrowing within 48 months of baseline. We defined a gradual onset of OA as someone who had one or more knees increase in radiographic scoring within 48 months; this would include someone who developed a possible or definite osteophyte. We defined the index visit as the study visit when a participant met the criteria for accelerated or gradual onset of knee OA. Our study period included up to three years before and after the index visit.

Our primary outcome variable was self-reported knee pain, based on the WOMAC (Western Ontario and McMaster Universities Arthritis Index) pain score.18 We explored 11 other secondary outcome measures: knee-specific disability (WOMAC function score), global impact of arthritis (single question with a 0 [very good] to 10 [very poor] response), walking pace, chair-stand pace, maximum isometric knee extension force, maximum isometric knee flexion force, physical activity level  (Physical Activity Score for the Elderly), physical health (Short-Form 12 Physical Component Score), mental health (Short-Form 12 Mental Component Score), depression (Center for Epidemiologic Studies-Depression Scale), and use of prescription medicines. To determine the number of prescription medications a participant used in the 30 days prior to a study visit, study staff asked participants to bring in all of their prescription medications, regardless of reason prescribed.

We found that adults who developed accelerated knee OA had greater knee pain, knee-specific disability, and greater global impact of arthritis and slower walking and chair-stand pace compared with those with a more gradual onset of knee OA.17 These findings were true regardless of the study time point (before or after index visit). Hence, people with accelerated knee OA experienced greater pain and functional limitations up to three years before and after they developed accelerated knee OA. We found no differences for maximum isometric knee extension or flexion force, physical activity level, physical or mental quality of life, depression, or use of prescribed medicines.17

4Knee-iStock46162162Despite the possibility of an interaction between group and time for knee pain, it was not statistically significant. However, we did find differences between groups related to changes in certain outcomes over time. We found that both groups started with similar chair-stand pace, but individuals with a gradual onset of knee OA subtly and gradually improved over time, while adults who developed accelerated knee OA gradually slowed until their index visit, then fluctuated over time.17 Furthermore, individuals with a more gradual onset of knee OA were steadily less likely to report greater global impact of arthritis at each visit before the index visit, while those who developed accelerated knee OA were more likely to report greater global impact of arthritis during the same time period.17

We found that adults with accelerated knee OA are more likely to report greater pain severity and experience more functional limitations than those with a more gradual onset of knee OA, regardless of time. We also found that adults with accelerated knee OA often report being more affected by their knee symptoms and have diminished performance on a functional test (chair-stand) years before developing advanced-stage knee OA. We found a similar, though not statistically significant, trend for self-reported knee pain.

Our findings underscore that accelerated knee OA is a painful and disabling type of OA that warrants more attention. Clinicians should be concerned about patients without radiographic OA who report knee pain, because it may be an early symptom of accelerated knee OA.

Early MRI evidence

An important question for clinicians is why someone might experience knee pain years before they develop accelerated knee OA. It is possible that adults who develop accelerated knee OA are initially developing subtle changes that fail to appear on conventional knee x-rays but are related to knee pain.14,19 In our preliminary analyses, we found that 18 adults with incident accelerated knee OA often had cartilage damage and meniscal pathology that was apparent on MRI before any radiographic evidence of accelerated knee OA.14

These findings agree with those of other investigators who have used MRI to show that adults with no radiographic OA had a high prevalence of cartilage damage (76%), bone marrow lesions (61%), and meniscal pathology (>20%).19 In that study sample, these lesions were associated with having knee symptoms and developing new symptoms.19 Furthermore, the presence of effusion or synovitis and meniscal pathology may predict radiographic OA two years later.20 Therefore, clinicians may be able to use MRI to identify high-risk adults who report knee pain without radiographic OA. This is a particularly appealing option if a patient has already had a recent knee MRI, if the clinician was already planning to order an MRI to rule out other pathologic findings (eg, acute meniscal tear), or if the cost of MRI decreases.

We used the findings from this study to clarify a conceptual model for the origin of accelerated knee OA (Figure 1). As mentioned earlier, we found in our prior work that being older and overweight are key risk factors for accelerated knee OA.13 Furthermore, aging19,21,22 and being overweight or obese19,23,24 are associated with cartilage damage, bone marrow lesions, and meniscal pathology, which are related to knee symptoms among adults without radiographic OA.19 Knee pain among those without radiographic OA is particularly concerning because knee pain is a risk factor for a new self-reported knee injury25 that is severe enough to limit a person’s ability to walk for at least two days. This new injury could be a trigger for accelerated knee OA.13

Once someone with accelerated knee OA develops advanced-stage knee OA, they are likely to report greater pain and experience more functional limitations for at least the next three years compared with individuals who have had a more gradual onset of knee OA. To prevent this sequela, it is vital that clinicians recognize the need to be more proactive with patients without OA who report knee pain because their pain could be early evidence of accelerated knee OA and will need to be managed accordingly.

Once a patient is considered high risk for accelerated knee OA, clinicians should treat the patient based on knee OA treatment guidelines. Most OA treatment guidelines26 advocate managing symptoms not just with pharmacological interventions, but also with exercise programs, which could include goals for pain modification and injury or fall prevention. This treatment strategy is low risk and could help prevent a new injury that may trigger the onset of accelerated knee OA; however, this is not yet proven.

Conclusion

Accelerated knee OA is a painful and disabling type of OA in which symptoms and functional limitations may precede the rapid development of advanced-stage knee OA. Furthermore, the effect of accelerated knee OA may linger for at least three years after the onset of advanced-stage knee OA. Clinicians should be concerned about adults without radiographic OA who report knee pain because it may be an early sign of accelerated knee OA.

Jeffrey B. Driban, PhD, ATC, CSCS, is an assistant professor at Tufts Medical Center and Tufts University in Boston.

Disclosure: Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01 AR065977. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health. The author has no financial relationships that would influence this manuscript. 

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