The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies.

This article reviews the pathogenetic role of metabolic disorders, which are of paramount relevance to the progression of tendon damage. In diabetes, the prevalence of rheumatological diseases is high, mainly because of the deleterious effects of advanced glycation end products that deteriorate the biological and mechanical functions of tendons and ligaments. In heterozygous familial hypercholesterolaemia, most patients develop Achilles xanthomatosis, a marker of high risk for cardiovascular disease caused by cholesterol deposition in the tendons. Tendon degeneration has also been observed in non-familial hypercholesterolaemia. Monosodium urate crystal deposition in soft tissues is a hallmark of chronic gouty arthritis. In this group of diseases, the mobilization of cholesterol and uric acid crystals is presumably followed by low-grade inflammation, which is responsible for tendon degeneration. Adiposity may contribute to tendon disorders via two different mechanisms: increased weight on the load-bearing tendons and systemic dysmetabolic factors that trigger subclinical persistent inflammation. Finally, tendon abnormalities have been observed in some rare congenital metabolism disorders such as alkaptonuria.

The prevalence of rotator cuff tears increases with age and several studies have shown that diabetes is associated with symptomatic shoulder pathologies. Aim of our research was to evaluate the prevalence of shoulder lesions in a population of asymptomatic elderly subjects, normal and with non insulin - dependent diabetes mellitus.

Cigarette smoking has deleterious effects on the musculo-skeletal system. The loss of bone mineral content and increased incidence of fractures are the best known negative consequences. The pathogenesis is complex, due to direct toxic effects on osteoblasts/osteoclasts activity of nicotine, and indirect actions on sex and adrenocortical hormones, vitamin D, intestinal calcium absorption, vessels and oxygen supply. Smoking may favour the onset or aggravate the progression of rheumatoid arthritis and back pain. Negative influences have been observed on muscle and on tendons. Moreover, smoking habit is associated to a number of short term post-operative complications and higher resource consumption. Smoking cessation is highly advisable with positive effects on the bone metabolism on the long term. More positive and immediate results can be obtained in patients submitted to orthopedic surgery: the healing process is improved, the frequency of complications is reduced, and the length of hospital stay is shortened.

Several rheumatologic manifestations are more pronounced in subjects with diabetes, ie, frozen shoulder, rotator cuff tears, Dupuytren's contracture, trigger finger, cheiroarthropathy in the upper limb, and Achilles tendinopathy and plantar fasciitis in the lower limb. These conditions can limit the range of motion of the affected joint, thereby impairing function and ability to perform activities of daily living. This review provides a short description of diabetes-related joint diseases, the specific pathogenetic mechanisms involved, and the role of inflammation, overuse, and genetics, each of which activates a complex sequence of biochemical alterations. Diabetes is a causative factor in tendon diseases and amplifies the damage induced by other agents as well. According to an accepted hypothesis, damaged joint tissue in diabetes is caused by an excess of advanced glycation end products, which forms covalent cross-links within collagen fibers and alters their structure and function. Moreover, they interact with a variety of cell surface receptors, activating a number of effects, including pro-oxidant and proinflammatory events. Adiposity and advanced age, commonly associated with type 2 diabetes mellitus, are further pathogenetic factors. Prevention and strict control of this metabolic disorder is essential, because it has been demonstrated that limited joint motion is related to duration of the disease and hyperglycemia. Several treatments are used in clinical practice, but their mechanisms of action are not completely understood, and their efficacy is also debated.