Michele Abate

Pathogenesis of tendinopathies: inflammation or degeneration?

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.

Occurrence of tendon pathologies in metabolic disorders

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.

Trail Making Test Predicts Physical Impairment and Mortality in Older Persons

OBJECTIVES: To examine whether performance in the Trail Making Test (TMT) predicts mobility impairment and mortality in older persons.

From Chronic Low Back Pain to Disability, a Multifactorial Mediated Pathway: The InCHIANTI Study

Study Design. Clinicoepidemiologic study in the Chianti area (Tuscany, Italy). Objective. To evaluate whether performance measures of lower extremity function confounds the association of low back pain (LBP) with self-report disability in specific basic and instrumental activities of daily living (IADLs). Summary of Background Data. LBP is high prevalent in older population and has a negative impact on functional status. Studies on the pathway leading from LBP to disability are limited and often the role played by important confounders is not considered. Methods. A total of 956 InCHIANTI study participants aged 65 and older able to complete performance-based tests of lower extremity function were included in this analysis. LBP was defined as a self-report of back pain “quite often-almost every day” in the past 12 months. Lower extremity function was evaluated administering the Short Physical Performance Battery. In addition, participants were asked to walk on a 7-m course and collect an object from the ground. Depressive symptoms (CES-D score), trunk flexion–extension range of motion, and hip–knee–foot pain were also considered in the pathway from LBP to disability. Results. Compared with participants who did not report LBP, those with LBP were more likely to report difficulty in performing most activities of daily living. LBP was also associated with disability in the activities of bathing, doing the laundry, performing heavy household chores, cutting toenails, shopping, and carrying a shopping bag. The association between LBP and disability in selected ADLs and IADLs was no longer statistical significant, after adjustment for performance in lower extremity function, with exception of the activity of “carrying a shopping bag”. Conclusion. The cross-sectional association between LBP and self-reported disability, in specific tasks is modulated by performance measures. Specific performance-based tests that explore the functional consequences of LBP may help design specific interventions of disability prevention and treatment in patients with LBP.

Limited joint mobility in diabetes and ageing: recent advances in pathogenesis and therapy.

Limited joint mobility is frequently observed in elderly people and in patients suffering from diabetes, who represent a growing segment of the population of western countries. Our review wishes to offer the “state of art” about this interesting topic, which may have important clinical implications, leading to impairment of both basic and instrumental activities of daily living. The main causes of a reduced range of motion are degenerative joint diseases and increased stiffness of collagen tissue. The main biochemical abnormality, common to aging and diabetes, is the non-enzymatic glycosilation of collagen, with advanced glycation end product (AGE) formation, which in turn leads to an increase of collagen cross-links. The most extensive accumulation of AGEs occurs in tissues that contain proteins with low turnover, such as the collagen in the extracellular matrix of articular capsule, ligaments and muscle-tendon units. The increase in collagen cross-linking alters the mechanical properties of these tissues with a decrease in elasticity and tensile strength, and an increase in mechanical stiffness. Besides this, AGEs react with specific cell surface receptors (RAGEs). The engagement of the ligand by RAGEs triggers cell-specific signalling, resulting in enhanced generation of reactive oxygen species and sustained up-regulation of pro-inflammatory mediators and adhesion molecules. An appropriate control of the glucose levels and a diet rich in antioxidant agents are recommended in patients with diabetes. Stretching and strengthening programmes are widely used, in order to prevent and to reduce joint stiffness, but the improvements with physiotherapy are little and short-lasting. Several drugs, which can interfere with AGE formation and removal, or with the cellular effects of AGEs, are under study (among them pyridoxamine, an active form of Vitamin B6, AGE-breaker compounds, glucosamine, rutin and derivatives, soluble RAGE isoforms, and statins). In experimental animal models, these drugs are effective in reducing diabetic complications due to AGE formation; however, further study is necessary before their extensive use in the clinical setting.

Sonographic evaluation of the shoulder in asymptomatic elderly subjects with diabetes.

BackgroundThe 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.MethodsThe study was performed on 48 subjects with diabetes and 32 controls (mean age: 71.5 ± 4.8 and 70.7 ± 4.5, respectively), who did not complain shoulder pain or dysfunction. An ultrasound examination was performed on both shoulders according to a standard protocol, utilizing multiplanar scans.ResultsTendons thickness was greater in diabetics than in controls (Supraspinatus Tendon: 6.2 ± 0.09 mm vs 5.2 ± 0.7 mm, p < 0.001; Biceps Tendon: 4 ± 0.8 mm vs 3.2 ± 0.4 mm, p < 0.001). Sonographic appearances of degenerative features in the rotator cuff and biceps were more frequently observed in diabetics (Supraspinatus Tendon: 42.7% vs 20.3%, p < 0.003; Biceps Tendon: 27% vs 7.8%, p < 0.002).Subjects with diabetes exhibited more tears in the Supraspinatus Tendon (Minor tears: 15 (15.8%) vs 2 (3.1%), p < 0.03; Major tears: 15 (15.8%) vs 5 (7.8%), p = ns), but not in the long head of Biceps. More effusions in subacromial bursa were observed in diabetics (23.9% vs 10.9%, p < 0.03) as well as tenosynovitis in biceps tendon (33.3% vs 10.9%, p < 0.001).In both groups, pathological findings were prevalent on the dominant side, but no difference related to duration of diabetes was found.ConclusionsOur results suggest that age - related rotator cuff tendon degenerative changes are more common in diabetics.Ultrasound is an useful tool for discovering in pre - symptomatic stages the subjects that may undergo shoulder symptomatic pathologies.

Frailty of older age: the role of the endocrine--immune interaction.

The so-called demographic transition has changed the age structure of the population worldwide, with profound effects on societal organization. The growing number and percentage of old and very old people has compelled the scientific community to focus on age related diseases and peculiar consequences of aging itself such as disability and frailty. Understanding the pathophysiology of frailty, a syndrome characterized by a reduced functional reserve and impaired adaptive capacity that results from cumulative declines of multiple subsystems, and causes increased vulnerability to adverse outcomes, is a major topic in aging research. Aging processes induce multiple changes in the hormones network (menopause, andropause, somatopause and adrenopause), in the immune system, and can modulate their efficiency and effectiveness in determining a response to stressors. These triggering events can unmask frailty in older people. Starting from these assumptions, we analyzed the relationship of the endocrine and immune networks in aging and in the different domains that are characteristically associated with the frailty syndrome, such as disability and sarcopenia, as well as in diseases related to aging such as Alzheimers dementia and Congestive Heart Failure.

Cigarette smoking and musculoskeletal disorders.

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.

Sarcopenia: age-related skeletal muscle changes from determinants to physical disability.

Human aging is characterized by skeletal muscle wasting, a debilitating condition which sets the susceptibility for diseases that directly affect the quality of life and often limit life span. Sarcopenia, i.e. the reduction of muscle mass and/or function, is the consequence of a reduction of protein synthesis and an increase in muscle protein degradation. In addition, the capacity for muscle regeneration is severely impaired in aging and this can lead to disability, particularly in patients with other concomitant diseases or organ impairment. Immobility and lack of exercise, increased levels of proinflammatory cytokines, increased production of oxygen free radicals or impaired detoxification, low anabolic hormone output, malnutrition and reduced neurological drive have been advocated as being responsible for sarcopenia. It is intriguing to notice that multiple pathways converge on skeletal muscle dysfunction, but the factors involved sometimes diverge to different pathways, thus intersecting at critical points. It is reasonable to argue that the activity of these nodes results from the net balance of regulating mechanisms, as in the case of the GH/IGF-1 axis, the testosterone and Cortisol functions, the pro- and anti-inflammatory cytokines and receptors. Both genetic and epigenetic mechanisms operate in regulating the final phenotype, the extent of muscle atrophy and reduction in strength and force generation. It is widely accepted that intervention on lifestyle habits represents an affordable and practical way to modify on a large scale some detrimental outcomes of aging, and particularly sarcopenia. The identification of the molecular chain able to reverse sarcopenia is a major goal of studies on human aging.

Management of limited joint mobility in diabetic patients

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.