oa Editorial [Hot Topic: Waiting for Action on the Osteoarthritis Front (Guest Editors: Virginia Byers Kraus and Thomas Aigner)]

Osteoarthritis is among the most common pathological conditions in archeological skeletal collections and is the most frequent musculoskeletal disorder in contemporary populations [1]. Worldwide, symptomatic osteoarthritis affects 9.6% of men and 18.0% of women aged over 60 years (http://www.who.int/chp/topics/rheumatic/en/ WHO Chronic Rheumatic Conditions). As of 2005, 27 million Americans had clinical osteoarthritis [2]. It is second to heart disease as the predominant cause of functional decline in the elderly and overall costs approximately 0.7% of the US gross domestic product [3]. These may be gross underestimates as recent analyses suggest that OA in the developed world may be under-diagnosed by 90% [4]. By the year 2020, when one out of every two Americans will be over the age of 50, the Centers for Disease Control forecasts that there will be a larger increase in new cases of arthritis than of any other disease in the United States (http://www.hss.edu/ conditions_14135.asp). Given these statistics, it is surprising that a national and even global sense of urgency is lacking regarding the need for definitive disease modifying osteoarthritis therapies. The state of the public perception of osteoarthritis is not unlike that of malaria in the year 1800. Malaria at that time was the most common illness on the American frontier but considered ‘a part of life, like hard work’. Many refused to regard it as a disease [5]. Although osteoarthritis researchers recognize that the designation ‘osteoarthritis’ encompasses a common endstage of many subforms of disease with different etiologies (genetic, injury, and metabolic, among others), the predominant medical and public perception persists of osteoarthritis as a “wear-andtear” phenomenon and inevitable consequence of aging. Without a sense of urgency, how are we to arrive at the goal of discovering and validating remittive therapies for osteoarthritis and get beyond the perception that osteoarthritis is an inevitable consequence of aging? On the other hand, is a sense of urgency called for when we can't do anything about it? This ‘catch 22’ can only be overcome by deliberately and steadfastly tackling the many barriers to achieving a cure, not the least of which are barriers in the minds of osteoarthritis researchers and drug developers themselves. The papers in this edition elucidate recent science related to many tractable osteoarthritis targets for development of agents that could be delivered either systemically or intra-articularly. In addition, here I would like to draw three analogies to other chronic diseases to highlight the need for new conceptions of osteoarthritis, with the hope that this paradigm could promote the transformation of osteoarthritis into an actionable disease for which more than palliative therapies could be available. First, consider the fact that osteoarthritis is one of many distinguished silent killers that work insidiously, often over decades, to finally kill an organ. In the case of osteoarthritis, it is the joint organ. Parallels with other silent killers include the killer of bones - osteoporosis; the killer of multiple organs including the brains and kidneys - hypertension; and the killer of hearts - atherosclerotic coronary artery disease (Fig. 1). Viewed through the lens of this paradigm, osteoarthritis would seem eminently amenable to treatment given the success to date developing definitive therapy to prevent and treat these other major chronic disease entities and silent killers.