Rationale: Osteoarthritis (OA) of the knee is a common cause of pain and disability, especially in people over the age of 65. In the current health care system both conservative (e.g. intra-articular injections with corticosteroids) and surgical (total knee replacement, TKR) treatment are applied. Although frequently used, certain effects of these treatments on protein metabolism remain unclear. It is well known that maintenance of different tissues is determined by a dynamic balance between protein synthesis and breakdown rates, with temporary changes in either protein synthesis or breakdown allowing net protein accretion or loss. Though protein supplementation has shown to be an effective nutritional strategy in stimulating muscle protein synthesis, it remains unclear to what extent other musculoskeletal tissues are able to respond to dietary protein supplementation. Therefore, the current study assesses the impact of preoperative protein supplementation on protein synthesis in different musculoskeletal tissues of the knee.

Objective: To investigate the effect of preoperative protein supplementation on Hoffa's fat pad, synovium, tendon, bone, muscle, ligament, menisci, and cartilage protein synthesis of the OA knee.

Study design: Randomized, parallel (two groups) study design. The intervention group will be compared to the control group.

Study population: 24 adults with OA of the knee undergoing TKR. Intervention: Daily 40 g of pre-sleep protein two weeks before TKR or no intervention.

Main study parameters/endpoints: Primary study parameters include protein synthesis rates and enrichments of Hoffa's fat pad, synovium, tendon, bone, muscle, ligament, menisci, and cartilage. Secondary parameters include whole-body protein synthesis, breakdown, oxidation, and net balance.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risks involved in participating in this study are minimal. There are no potential effects known for the ingestion of protein. Muscle biopsies and tissue collection will be performed during the surgical procedure.

Inclusion Criteria:

• Written informed consent
• Male and female patients scheduled for total knee arthroplasty
• BMI between 18.5-30 kg/m2
• Age > 18 years
• Mentally competent, as judged by the treating physician
• Functioning gastrointestinal tract, eligible for oral protein supplementation

Exclusion Criteria:

• Corticosteroid injections less than 3 months prior to participation
• Any medications know to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescription strength acne medications)
• Lactose intolerance
• Insulin-dependent diabetes mellitus
• Alcohol abuse
• Rheumatoid arthritis
• Peripheral artery disease Fontaine III or IV
• COPD GOLD III or IV
• Phenylketonuria
• Surgical intervention in the past four weeks
• Total parenteral nutrition at day of surgery
• Neoadjuvant chemotherapy or radiotherapy
• GFR <20 mL/min/1.73 m2
• Osteoarthritis of the knee secondary to septic arthritis, osteonecrosis, fracture, OD, or malignant processes
• Collagen disorders, e.g. Marfan and Ehler-Danlos
• Any other medical condition that may interfere with the safety of the subjects or the outcome parameters, in the investigators judgement
• Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol instructions
• Participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study