Recent developments and future research in the bone and joint decade 2000-2010.

Abstract

Musculoskeletal disorders encompass a broad spectrum of conditions of multifactorial origin and very different clinical appearance. Connective tissues are primarily affected in osteoporosis and joint diseases such as osteoarthritis and rheumatoid arthritis, which cause severe long-term pain and physical disability and give rise to heavy costs to society. Many of the major connective tissue diseases involve inflammatory mechanisms. Rheumatoid arthritis, psoriasis, and systemic lupus erythematosus are among the last-remaining widespread diseases for which the scientific community has insufficient knowledge of pathogenesis or treatments that can prevent or reverse the disease course. Mechanisms and pathways leading to destructive inflammation may to a large extent be shared among these diseases and may also operate in other conditions such as osteoarthritis, vasculitis, arteriosclerosis, and osteoporosis. This is clearly demonstrated in genetic studies of animal models in which many genes have been shown to be associated with a wide spectrum of inflammatory diseases, and many diseases include components of spreading the inflammation to various other organs. One prominent example is rheumatoid arthritis, in which vasculitis and increased arteriosclerosis morbidity occur. It is also important to take into account that the mere occurrence of widespread inflammatory diseases in humans is likely to be caused not only by rapidly changing environmental factors but also by natural selection for protection against infectious diseases. In addition, there is often a connection between infections, especially chronic infections, and inflammatory diseases. Most inflammatory diseases affect connective tissues, either by inducing catabolic events or by triggering repair attempts; both will lead to altered function and may develop further to fibrosis. Key features of connective tissues are to take up and distribute load and to provide a barrier and protective function, as well as to retain shape. The component of tissue destruction may be initiated by factors such as mechanical overload that brings the normally very dynamic turnover out of balance. This turnover is aimed at replacing fatigued tissue, for example, with new and mechanically more stable tissue. Many factors govern the basis for this remodelling in connective tissues. Exaggerated load will lead to damage and a higher risk for initiation of a pathological process. In addition, inflammation is a condition that will affect the metabolism in connective tissue cells and usually hamper their ability to repair. This is likely to increase the sensitivity to mechanical load and may perhaps drive the process into a pathological condition. Interestingly, components released from connective tissues as a result of a pathological process appear to have the capability to modulate the inflammatory response and in some cases also to trigger autoimmune reactions. It is thus becoming apparent that the reactions in connective tissues leading to tissue damage are extensively influenced by environmental factors, including vascular and nerve ingrowth and local inflammation. The gap between biology and clinical research The wide gap between clinical approaches and more basic approaches to understanding the disease mechanisms has been difficult to overcome. The clinically oriented approach had its golden age decades ago, when empirical observations could lead to major breakthroughs and built the basis of today's clinical practice. It has, however, shown clear limitations in solving the pathways of disease: some of the treatments given today still have no rational explanation or produce side-effects because of unspecific targeting. The molecular approach has recently been successful in providing tools such as the genome sequence, specific molecular structure and tissue composition but has not yet been significantly explored in understanding disease processes. …