Muscle weakness, with corticosteroids

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

For some patients, cessation of tryptophan ingestion led to resolution of the symptoms in other patients the use of high dose corticosteroids appeared to be helpful. However, for some patients, the disease evolved into a chronic phase, with cutaneous, neuromuscular, pulmonary, cardiac, and cognitive involvement. The most common features of chronic EMS are fatigue, muscle cramping, myalgia, paraesthesias with objectively demonstrated hypes-thesias (lessened sensitivity to touch), chronic joint pain, scleroderma-like skin changes, and proximal muscle weakness. In one study, 88% of EMS patients continued to manifest more than three of these clinical symptoms after 3 years. 

Similar serum enzyme elevations are found in polymyositis (A3, B4a, B20, D2, D17, E5, H7, KIO, M15, M18, Pl, P4, P5, P7, R15, S15, S26, T8, W12, W19), a nonspecific inflammatory myopathy sometimes associated with neoplastic disease but in general related to the collagen diseases and likewise responsive to corticosteroid therapy. The condition occurs at all ages in both sexes, may be acute or insidious with perhaps a normal erythrocyte sedimentation rate, may or may not be painful, or may be accompanied by an erythematous rash (dermatomyositis). Characteristically the earliest appearance of weakness is in the muscles of the pelvic... 

Like the other conditions discussed above, patients with COPD have a higher prevalence of hypogonadism than their healthier counterparts [240]. Chronic steroid use may exacerbate muscle loss and weakness in this group. Although unproven, treatment of these symptoms with a SARM could offer considerable improvement of quality of life in these patients as well as those who are treated with chronic corticosteroids for rheumatologic or other inflammatory diseases. These are examples of chronic conditions where decades of anabolic therapy may be needed. An anabolic agent that reduces the morbidity and mortality associated with these conditions without unwanted effects would serve a huge unmet need in this patient population. 

There are other metabolic affects associated with chronic corticosteroid use including redistribution of fat giving the typical moon face and buffalo hump hyperglycaemia and possible diabetes protein loss from skeletal muscles with wasting and weakness increased bone metabolism leading to osteoporosis and growth inhibition in children due to early closure of the epiphyseal plates in long bones. 

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