Faculty Bibliography

Purpose: To assess whether variability in caudal X-ray beam angulation (CBA) improves alignment of the medial tibial plateau (MTP) versus a fixed 10degree CBA, using non-fluoroscopic fixed-flexion knee radiographs. Methods: 133 subjects with knee OA underwent fixed-flexion AP X-ray examinations as part of a longitudinal study. We performed a cross sectional substudy in which 90 subjects were imaged with a 10degree CBA (Method 1) and 43 subjects were imaged using different CBAs (choosing from 5degree, 10degree, 15degree) determined by a trained radiology technician, depending on MTP alignment assessed in real time (Method 2). After reading a blinded training set of radiographs, an experienced radiologist, who was blinded to patients and method used, read the x-rays for MTP alignment quality using a 1-5 scale (1, 2=good, 3=acceptable, 4= poor, 5= unacceptable), and for Kellgren-Lawrence (KL) grade. Results: Method 1 subjects (10degree angulation): MTP alignment quality was scored as good or acceptable 62% and 69% of the time for the right and left knees, respectively. Method 2 subjects (variable angulation): Variable angulation resulted in good or acceptable MTP alignment quality on at least one x-ray 86% and 88% of the time for right and left knees, respectively. When CBA was changed, MTP alignment quality changed 84% of the time for the right knee and 77% of the time for the left knee in subjects who had at least 2 radiographs (n=43). The KL grade changed 28% and 46% of the time in the right and left knees, respectively, when MTP alignment quality changed in the same knee. The KL grade changed 38% and 36% of the time in the right and left knees, respectively, when there was no change in MTP alignment quality but there was a change in CBA. A change in CBA resulted in MTP alignment quality change in bilateral knees 66% of the time, of which this change was in the same direction (improved vs worsened) 86% of the time. Using a CBA of 10degree resulted in improved (over other angulations) MTP alignment quality 53% and 50% of the time for the right and left knees, respectively. Using a CBA of 10degree resulted in worsened MTP alignment 33% and 22% of the time for right and left knees, respectively. Conclusion: While fixed 10degree CBA in fixed-flexion radiographs results in acceptable or good MTP alignment quality the majority of the time, variable CBA improves this frequency in knee OA subjects. Changes in CBA often change the MTP alignment quality, usually in the same direction in both knees, and sometimes change the KL grade. More studies are needed to determine the optimal CBA for non-fluoroscopic fixed-flexion protocols and all radiographic knee OA studies should report the specific techniques used, including CBA

While research in osteoarthritis has focused on the events that lead to the destruction of articular cartilage, recent evidence suggests that two other components of the joints-bone and synovium-also play key roles in pathogenesis. All three tissues undergo alterations in concert at the structural levels in response to mechanical stress and joint malalignment. Advanced imaging studies such as MRI support this interdependence, revealing the classical changes of joint space narrowing and cartilage degeneration as well as the more recently appreciated bone marrow lesions and synovitis that may correlate with clinical symptoms. Molecular evidence also points to a coordinated release of cytokines and other inflammatory mediators from each of the three tissues together in progression of disease, although we are still in search of biochemical signatures that will predict the subset of patients who progress more quickly-and who will provide key clues to successful molecular targets in future therapies. At this time we lack definitive evidence pointing to which, if any, of the three tissues should serve as the main target for disease modification or structure protection, although most efforts have focused on cartilage. Thus current therapies focus on controlling symptoms, while research efforts search for reliable imaging and molecular biomarkers to help guide future trials of potential disease-modifying agents

Osteoarthritis (OA) is often a progressive and disabling disease resulting from a combination of risk factors, including age, genetics, trauma, and knee alignment, as well as an imbalance of physiologic processes resulting in inflammatory cascades on a molecular level. The synovium, bone, and cartilage are each involved in the pathophysiological mechanisms that lead to progressive joint degeneration, and, thus, also serve as targets for therapies. Efforts to identify disease-modifying osteoarthritis drugs (DMOADs) have been hampered by several factors, but the focus has now shifted toward the validation of chemical and imaging biomarkers that should aid in DMOAD development. In this review, we summarize current pathological mechanisms occurring in the individual but interconnected compartments of OA joints, as well as discuss related therapeutic interventions that are currently available or on the horizon

Biologic therapies have emerged as important treatments in chronic inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, and are now garnering more attention in the vasculitides. These agents, including tumor necrosis factor-alpha inhibitors, B-cell-depleting agents, interferon-alpha, and some antiviral treatments, target specific components of the immune system and may have lower side effect risk profiles than the conventional immunosuppressives and cytotoxic agents. This article addresses the encouraging data and the possible pitfalls of these new therapeutic options, thus far evaluated mostly by case reports, small series, and open-label trials. Confirming the efficacy of existing and newer therapies will require further clinical investigation through randomized placebo-controlled studies to identify the proper doses and treatment schedules and single out those drugs that may expose patients to dangers that outweigh the potential benefits.