Acidic environment induces local reactive tenosynovial physical-chemical inflammatory changes with proliferation of the mesenchymal tissue, subsequent retraction and tenosynoviosclerosis. Such changes develop also in conjunction with inflammatory processes of joints, their capsules and periarticular structures, as well as metabolic disturbances associated with collagen I disorder. Mechanical negative factors arising from functional impairment of muscles and ligaments contribute to structural changes, mainly in their attachments. Long-term retraction, subsequent loss of elasticity and protracted increased tension in attachments induce enthesopathic ossification. Metabolic enthesopathies constitute a heterogeneous group of enthesopathies occurring in various metabolic diseases [56] (Fig. 16.3).

It is believed that insulin resistance is the underlying condition of metabolic syndrome and that accumulation of ectopic fat has an impact on whole body metabolism of carbohydrates and on pathogenesis of insulin resistance in the muscle tissue.

The flow of muscle fatty acids as the source of oxidative energy probably plays a key role in the onset and development of muscle abnormalities and in the whole body metabolism and is potentially involved in pathogenesis of obesity, MS and type 2 DM. Impaired metabolic flexibility of carbohydrate and lipid metabolism contributes to failure of skeletal muscle to appropriately move between the use of lipid in the fasting state and use of carbohydrate in the insulin-stimulated prandial state. This inflexibility results in reduced mitochondrial size and density, which is typical of MS, mainly in obese and diabetic individuals.

Peripheral neuropathy resulting from metabolic disorders causes regulation changes in motor, sensitive and autonomic innervation of muscles. Loss of nociception and proprioception, mainly in elderly patients with a long history of type 2 diabetes, neuromicroangiopathy with perfusion disturbances, trophic changes in the skin, muscle weakness and lower speed of muscle action, arising from microangiopathy-related endothelial neuropathy of muscles with impaired neuroregulation and with collagen degradation and limitation of functional qualities of the muscular tissue by decreased oxidation constitute the complex causes of muscle changes in MS.

The first to describe diabetic muscle infarction were Angervall and Stener in 1965 [3]. It is one of the late complications in elderly individuals with type 2 diabetes affected also by other systemic disorders, mainly retinopathy and nephropathy and in patients requiring dialysis.

The dominant factor in etiopathogenesis is neurogenic microangiopathy with subsequent disorder of tissue vascularisation. It has been hypothesised that chronic reductions in nitric oxide bioavailability contribute to a loss of skeletal muscle microcirculation, leading to impaired muscle perfusion with elevated metabolic demand [17].

Recent investigations demonstrate abnormalities in fatty acid metabolism and accumulation of ectopic fat in the skeletal muscles. The findings support a hypothesis about strong relationship between elevated intramuscular lipid levels and insulin resistance of all tissues in the body [51]. Peroxisome proliferator-activated receptors (PPARs) delta are transcription factors involved in both developmental and metabolic functions. These are activated by fatty acids, fatty acid metabolites and synthetic compounds marketed for their lipid-lowering and antidiabetic actions. Activation of PPARs – fat burning sensors – induces fatty acid beta-oxidation in striated skeletal muscle and attenuates metabolic syndrome. Nuclear receptors play a central role in the control of fatty acid burning in adipose and skeletal muscle tissues [21, 44, 52].

Diabetic muscle infarction is characterised by acute atraumatic painful swelling occurring most frequently in thigh or tibia muscles. The disease is not diffuse, but local, with occasional recurrences. Muscle tissue is exposed to local necrosis, healing with a scar.

The laboratory finding shows elevated erythrocyte sedimentation rate and most often normal or threshold leukocyte and creatinine phosphokinase levels. The most accurate diagnosis is provided by MRI.

A relatively rare form of muscle disease is the Bruns-Garland syndrome – diabetic muscle amyotrophy. It is an infrequent type of neuropathy that markedly affects the patient´s mobility. It occurs usually in patients with type 2 diabetes. It is clinically manifested by muscle pain in proximal lower limbs and their increasing weakness arising from perineural microangiopathy with chronically developing ischaemia of peripheral nerve fibres. The current opinions on etiopathogenesis prefer the theory that the disease results from inflammatory response of the walls of perineural capillary bed, induced by immunologic disorders. It is a clearly neuropathic disease despite the fact that its clinical manifestations in the early stages may be of myopathic nature.

Diabetic amyotrophy begins as a rule with unilateral pain in the thigh, hip, gluteal muscle or tibia. Occasionally it may occur in the acute form in both thighs, sometimes with predominance of one side, with the development of muscle weakness and later with atrophy of thigh muscles that can be first observed in quadriceps, but after several months, it progresses into adjacent muscle groups. It typically has subacute course with muscle pain and asymmetrical weakness up to hypotrophy of muscles of the hip. Occasionally the disease may involve muscles of the tibia and foot or rarely also upper limb muscles. This type of neuropathy affects predominantly elderly patients with type 2 DM. The associated lower limb weakness makes transition from sitting to standing impossible without assistance [34].

Reflex sympathetic dystrophy syndrome is also known as algodystrophic syndrome, Sudeck’s atrophy and type 1 complex regional pain syndrome. It is characterised by localised or diffuse pain usually in conjunction with swelling, trophic and vasomotor changes [41] and movement disorders. It may occur spontaneously, after trivial injury of soft tissue structures, fracture, distortion, or after surgical intervention in loco. Predisposing factors include diabetes mellitus, hyperthyroidism, hyperparathyroidism and type IV hyperlipidaemia [8].

Involvement of the musculoskeletal system in metabolic syndrome is general or local, with structural changes at predilection sites.

According to the nature of the affected structure, it is possible to distinguish between joint changes resulting from osteoarthritis and avascular necrosis of joint structures, capsular and pericapsular changes arising from calcification or ossification of various degree and chronic adhesions of joint capsules and muscle-tendon changes in the form of ossifying enthesopathies and tenosynoviosclerosis, muscle hypotrophy and infarction. Thecal structures – bursae – are affected less frequently.

Clinical findings include limited mobility of the spine or altered joint with different degree of pain, enthesopathic pain of tendon insertions and of hands, with digital flexor contractures and compression of the carpal tunnel structures, later loss of axial alignment, trophic changes and joint deformities partially resembling RA, mobility disorders and muscle weakness.

Generalised osteoporosis frequently accompanies metabolic disturbances, which may potentiate age-related disorders of calcium metabolism (hypoestrogenic, malabsorption) or induced osteoporosis.

A rare form is neuropathic Charcot diabetic spondyloarthropathy, a less frequent variant of neurogenic Charcot diabetic osteoarthropathy, often confused with degenerative spondylitic, osteochondrotic and spondylarthritic changes.

Charcot diabetic spondyloarthropathy (CHDS) develops after a long history of metabolic disorders, most often in type 2 DM.

Multifactorial etiopathogenesis of diabetic neuropathic CHDS includes the following contributing factors:

A specific form of involvement of both the spine and periphery is diffuse idiopathic skeletal hyperostosis (DISH), also known as Forestier’s hyperostotic spondylosis, where ossification of the spine, the long ligaments in particular, is associated with ossification in the periphery, mainly in the region of the shoulder and pelvic ligaments and manifestation of tenosynoviosclerosis and cheiroarthropathy.

DISH is characterised by new bone formation in the spine, calcification and ossification of vertebral ligaments and, in the periphery, by enthesopathy associated with periosteal as well as endosteal ossification [29, 35, 40, 55]. DISH is manifested by direct localised metaplastic calcification or ossification of the matrix in the thin mesenchymal tissue between the longitudinal ligament and vertebral body (most often polysegmental anterior longitudinal ligament) and secondary involvement of the ligament, as well as enthesopathies [29, 40, 55]. Metaplastic ossification may be direct, where false bone in tendon insertions is formed from mature fibrous structures through hyaline dystrophy and calcification of matrix and indirect which is preceded by the formation of granulation tissue with formation of osteoblasts. Dystrophic calcification is accompanied by calcification of matrix [55].

DISH exhibits features of flowing ossifications of vertebral bodies, fragmented ossifications, hyperostotic osteophytes and syndesmophytes of shapes typical of this manifestation of metabolic disorders (Fig. 16.4).

Osteophytic changes have a specific radiographic manifestation of various modifications typical of DISH (Fig. 16.5).

Criteria for DISH development and diagnosis are based on the Fornasier’s classification:

or Utsinger’s classification:

Possible DISH is diagnosed if criterion II or III is fulfilled (osteophytes must be in all locations).

Probable DISH is diagnosed if criterion II and III are fulfilled.

Definite DISH is diagnosed if criterion I is fulfilled.

Hyperostosis is bone tissue hyperplasia, mostly generalised.

This disease can be seen in persons over the age of 40, with obesity of metabolic-endocrine nature, with male predominance (male-female ratio of 2:1) [55]. Except for spinal stiffness, it does not always have marked clinical symptoms, unless it compresses medullary and radicular structures. In the advanced stage, it affects whole segments of the spine. Patients may develop secondary, trauma-induced localised hyperostosis. DISH is often associated with enthesopathies, most frequently in the pelvic ring, shoulders, weight bearing joints, and tenosynoviosclerosis of hand, less frequently of the foot, flexor tendons [38, 56].

These changes include: