Musculoskeletal diseases

The term “rheuma” is derived from the ancient greek and literally means something that flows, in direct allusion to the humor present in inflammed sites. This definition indicates the intuitive knowledge, from a long time ago, of the close relationship between inflammatory processes and rheumatic pathologies. Nowadays, the terms muculoskeletal or, the most generic rheumatic disease are generally accepted as synonyms to describe over two hundred different disorders involving many tissues and cell types. They especially affect the connective tissue structures, mainly in joints and related skeletal structures (tendons, ligaments, bones, and muscles) although some rheumatic diseases can also involve internal organs. In addition, several rheumatological disorders are associated with an increased incidence of malignancy.

Rheumatic diseases often show common symptoms, signs and clinical features hindering their correct diagnosis and characterization as a particular disease (Table 1). According to the the main target affected, they can be grouped in: Arthropathies (joint disorders), Systemic connective tissue disorders (autoimmune diseases afecting multiple organs), Dorsopathies (back disorders related to spine deformities or spine arthritis of inflammatory origin), Soft tissue disorders (involving muscles, tendons, synovium, etc.) and Osteopathies/Chondropathies (e.g. disorders related to bone density and structure like osteoporosis).

Whatever the cause, disorders of the musculoskeletal system are the most common cause of severe chronic pain and physical disability affecting millions of individuals along the world. Thus, their impact in individual quality of life and the direct and indirect costs related to morbidity and disability have important socioeconomic repercussions that have turned them into a public health problem, getting aggravated by increasingly aging of the population.

Despite advances in biological research, little is known about the exact etiology and pathogenetic mechanisms of many musculoskeletal disorders. Some factors like inherited cartilage weakness, injury or excessive stress on the joint are important to develop osteoarthritis. In other rheumatic diseases, the role that autoimmune processes play in the pathogenesis has been widely proven. In most of them, a genetic predisposition has been described, in particular, the influence of distinct HLA haplotypes in rheumatoid arthritis (RA), ankylosing spondylitis, systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). Aging, lifestyle, nutrition and infection are, in addition, known disease risk factors, however it is unclear how genetic predisposition in association to environmental factors leads to the development of disease only in certain individuals. As occurs in most autoimmune diseases, gender has a major role in the development of musculoskeletal pathologies clearly biased to a preponderance in females, with the only exception of ankylosing spondylitis. Prevalence of rheumatic diseases in the elderly has erroneously associated rheumatic diseases with old age, although they may start at any time from early childhood to old age.

Although targeting of proinflammatory cytokines and therapies directed against inflammatory cells has been during years the main target for treatment of rheumatic diseases, latest advances are focused on other promising strategies like gene therapy to deliver therapeutic proteins locally or regenerative medicine to replace damaged tissues using mesenchymal stem cells ability to differentiate into connective tissue.