Minimal to no inclusion.

Rationale: Situations such as fractures of the lower extremity can necessitate a prolonged period of immobilization in otherwise healthy individuals. Long-term immobilization of the lower extremity has shown to cause significant reductions in skeletal muscle mass, already occurring during the early stages of disuse. Accordingly, feasible strategies for attenuating this loss of muscle during disuse need to be pursued. Local neuromuscular electrical stimulation (NMES) offers such a potential strategy but, as yet, remains untested during prolonged muscle disuse in a clinical setting.

Objective: To investigate whether twice daily local (gastrocnemius/soleus) NMES attenuates muscle loss during 2 weeks of unilateral ankle immobilization.

Study design: Randomized, parallel (two groups) study design.

Study population: 30 adults (18-65 y) with any form of closed ankle fractures needing surgical treatment.

Intervention: Twice daily neuromuscular electrical stimulation (NMES) or no intervention.

Main study parameters/endpoints: Primary: Calf muscle (gastrocnemius) cross sectional area (CSA) as determined by CT scan. Secondary: type I and II muscle fiber CSA and SC content, intramuscular triglyceride content and mRNA and protein expression of anabolic signaling proteins.

Inclusion Criteria:

• Unilateral closed ankle fracture (Weber type A, B or C)
• Aged from 18-65 years
• 18.5 < BMI < 30 kg/m2
• Undergoing surgical treatment

Exclusion Criteria:

• Additional fractures beside ankle fracture (e.g. multi-trauma following a car accident)
• Use of oral anticoagulants such as vitamin K-antagonists (e.g. acenocoumarol and fenprocoumon) and direct-acting or new oral anticoagulants (e.g. apixaban, dabigatran and rivaroxaban).
• Any family history of thrombosis
• All co-morbidities interacting with mobility and muscle metabolism of the lower limbs (e.g. arthritis, spasticity/rigidity, all neurological disorders and paralysis).
• Myocardial infarction within the last 3 years