Knee lesions apparent on magnetic resonance imaging (MRI) and worsening over the subsequent 12 to 48 months predicted subsequent development of symptomatic, radiographically apparent knee osteoarthritis (OA). Early MRI data may help identify the best therapeutic window for early intervention in OA, before radiographic evidence of disease appears, according to a new study.

Leena Sharma, MD, from the Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, and colleagues, published their findings online October 14 in the Annals of the Rheumatic Diseases.

Jingbo Niu, MD, from the Clinical Epidemiology Research & Training Unit, Boston University School of Medicine, Massachusetts, and colleagues highlighted the potential of these "early warning" signs in a separate study published online September 28 in Arthritis & Rheumatology. In that study, the researchers identified "profiles" that predict development of either patellofemoral (PF) or tibiofemoral (TF) OA. The use of MRI remains solely a research tool at present, but it offers the chance to identify the earliest events that lead to OA and to refine patient selection in ways that might increase the possibility of identifying disease-modifying OA therapies in clinical trials.

Dr Sharma's group studied 849 participants in the Osteoarthritis Initiative with follow-up up to 84 months. All were Kellgren/Lawrence 0 on radiography at baseline and were considered to be high risk for knee OA because of knee symptoms, overweight, knee injury, knee surgery, family history of total knee replacement for OA in a parent or sibling, Heberden' s nodes, repetitive knee bending, and/or age 70 to 79 years. The researchers assessed cartilage damage, bone marrow lesions, and menisci on MRI at 12 months (baseline) and at 48 months. They then used multivariable logistic regression, adjusting for potential confounders including age, gender, body mass index, knee injury, and knee surgery to examine associations among baseline MRI and development of radiographically apparent OA, persistent symptoms, or OA medication use at 48 to 84 months.

"Worsening MRI lesion status between the 12- and 48-month visits in higher-risk participants with no knee OA was associated with new radiographic OA in the concurrent time period and persistent symptoms in the subsequent 3-year period," Dr Sharma told Medscape Medical News. She said these findings support the ongoing paradigm shift from considering OA to be a wear-and-tear disease of the cartilage to seeing OA pathogenesis as marked by two phases: compensated/stable and decompensated/progressive disease.

"These lesions (in knees without radiographic OA) are not incidental or trivial findings but represent early disease and illness. The paradigm shift suggested is toward investigation of tissue-targeted intervention effects at this early stage," Dr Sharma said.

In the related work, Dr Niu's team analyzed MRI data for 885 knees of patients in the prospective Multicenter Osteoarthritis Study, also with follow-up of 84 months. In an approach somewhat analogous to gene expression profiling, the researchers used latent class analysis to identify a constellation of MRI lesions in each joint that identified subgroups who subsequently developed radiographically apparent TF or PF osteoarthritis. The MRI lesions included cartilage damage, bone marrow lesion, meniscal tear, meniscal extrusion, synovitis, and effusion.

The researchers identified four latent subgroups for each joint and also found that meniscal damage played a different role in development of OA in the TF vs the PF joints. For the TF joint, the subgroups and associated odds ratios (ORs) for OA were minimal MRI lesions (OR, 1.0), mild lesions (OR, 5.6), moderate lesions with little meniscal involvement (OR, 1.8), and severe lesions (OR, 5.0). For the PF joint, the subgroups and associated odds ratios were minimal lesions (OR, 1.0), mild lesions (OR, 3.86), moderate lesions (OR, 5.1), and severe lesions with limited meniscal involvement (OR, 13.7).

The authors write, "The magnitude of lesions such as cartilage damage and co-existing meniscal damage appear to be the main distinction between the subgroups. Further, meniscal damage might play a prominent role in the development of incident [radiographic OA] in the [TF joint] but not the [PF joint]. Assessment of patterns of coexisting structural lesions provides novel and unique insights into the pathogenesis of OA."

David J. Hunter, MD, who coauthored with Leticia A. Deveza, MD, an editorial accompanying the Niu paper, told Medscape Medical News, "Both of these studies demonstrate that the pathologic disease process of osteoarthritis likely precedes radiographic evidence of the disease by a number of years. It is likely heterogeneous in nature and characterized by abnormalities in a range of synovial tissues including bone marrow lesions, synovitis, meniscal alteration, and hyaline cartilage abnormalities." Dr Hunter and Dr Deveza are both from the Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Australia.

One important omission from the Sharma article was that synovitis was not included, although it is an important feature predisposing to the development of osteoarthritis and pain, Dr Hunter commented.

Dr Hunter and Dr Sharma both emphasized that MRI currently has almost no role in the management of patients who have or are at risk for knee OA.

"It is important to note that these studies are important in developing our understanding of the disease, but at this point have no clinical implications for changing practice. The increasing frequency of the use of MRI is likely leading to inappropriate surgery, occurring particularly on meniscal abnormalities, which are concomitant with the disease process and are unlikely an important source of symptoms," Dr Hunter explained. "It is important for clinicians to note that obtaining MRIs on patients for that purpose of measuring or monitoring their osteoarthritis has very little, if any, value at this point in time, when we don't have disease-modifying agents available to us." He would use MRI in rare cases to document evidence of osteochondritis dissecans, avascular necrosis, or pigmented villonodular synovitis.

Dr. Sharma concurred with that, saying, "Given the absence of disease-modifying therapy for OA, widespread clinical application of MRI is difficult to justify. These findings have greatest implications for scientists who are developing pharmacological and nonpharmacological treatments, suggesting that they should consider prevention or delay of worsening of these early-stage lesions as a target, in an effort to prevent or delay full-blown disease. Candidate interventions should be studied at this stage, when they are more likely to be effective, potentially even in a shorter duration or intermittently applied."

Dr Sharma suggested that tissue-targeted trials might be done using MRI outcomes at earlier stages than commonly studied.

The Osteoarthritis Initiative is a public–private partnership. Private funding partners include Merck Research Laboratories, Novartis Pharmaceuticals Corporation, GlaxoSmithKline, and Pfizer, Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health. The authors and editorialists have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online October 14, 2015. Abstract

Arthritis Rheum. Published online September 28, 2015. Article abstract, Editorial extract