Hormonal

In human skeletal muscle disuse atrophy, muscle mass loss is primarily driven by a depression in protein synthesis (both fasted and fed states) rather than an elevation in protein breakdown (proteolysis).

When you immobilize a limb, your muscle shrinks mainly because it stops building protein, not because it actively destroys it. The muscle becomes 'resistant' to the normal building signals from food (amino acids). Therefore, simply trying to stop breakdown (e.g., with anti-catabolic drugs) may be less effective than addressing the failure of synthesis, potentially through mechanical loading or specific nutritional strategies that overcome this 'anabolic resistance', though the paper notes standard amino acid supplementation often fails to rescue this resistance in the short term.