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Musculoskeletal complications with sex steroid deprivation

Adjuvant hormone therapy commonly causes musculoskeletal complications in cancer patients. The mechanism(s) of androgen and estrogen deprivation-induced muscle dysfunction has not been identified, although both have been associated with increased inflammation and oxidative stress. The ryanodine receptor (RyR1)/calcium release channel on the sarcoplasmic reticulum is required for muscle excitation-contraction coupling. Pathological oxidation-dependent depletion of the stabilizing subunit calstabin from RyR1 results in leaky channels and impaired muscle function. We are interested in the effects of sex steroid deprivation on calcium handling, RyR1-calstabin stability and skeletal muscle contractility. Our aim is to determine whether pharmacological stabilization of the RyR1 channel might ameliorate muscle weakness in patients treated with adjuvant hormone therapy.