Metabolic Complications Following Knee Injury in Young and Middle Aged Patients

Hypothesis Implementation of a sedentary lifestyle with almost no physical activity in otherwise physical active individuals undergoing knee orthopaedic surgical procedures will during 6 weeks (4 to 8 weeks)

- derange insulin sensitivity and glucose effectiveness

- decrease disposition index

- imply hyper-secretion of incretin hormones and glucagon

- compensatory decrease in insulin clearance

- decrease lipid oxidation

- increase visceral adipose tissue

- increase number of low density lipoprotein particles and a decrease the particle size

- increase immune and low grade inflammatory response as measured in plasma and urine

- induce bone loss in hip as measured by bone mineral density (BMD)

- increase bone resorption and decrease bone formation as measured by selected bone turnover markers.

The proposed negative changes in bone, lipid and glucose metabolism are thought to reverse at least partly so, during active physical rehabilitation during week 6 through week 16.

Statistics Ten days of bed rest in 13 healthy young individuals showed a 20% (P<0.05) significant decrease in insulin sensitivity and a 50% (P<0.05) reduction in lipid oxidation. Thirty-one days of bed rest in 8 healthy women was significantly associated with bone loss in total hip (2.07%, P<0.001).

As the present study does not imply strict bed rest but exhibit a longer sedentary period of following up as the above studies and include a larger number of participants we are very likely to exhibit a power > 80% at significance level

Ethical issues The study is approved by the local scientific ethical committee and the Danish Data Protection Agency. The study adheres to the Danish Act on Processing of Personal Data and, Danish Act on Health and the Helsinki II convention of clinical trials. The study will be announced at the clinicaltrials.gov homepage. All participants are informed about the purpose of the study, all ethical issues and a written consent is obtained before participation.

Personal data from patient medical files will be accessed by principal investigator to gather information concerning the knee injuries in order to identify and characterize the knee injury for each subject. Personal data concerning demographic relations such as gender and age will be accessed as well to ensure the case subjects meet the inclusion criteria and for statistically use. To make assessments on study participation, the principal investigator will also gain access to relevant data from the patient s medical files concerning illnesses or conditions the case subject might report. The X-ray radiation from 1 DXA scan equals 1 day of background radiation in Denmark. Thus 3 DXA scans throughout the study period are equal to 3 days of background radiation. This amount of radiation is 30-fold less than that of a single standard CT-scan of abdomen. In other words the dose of radiation is so low that a calculation of risk is not possible.

The amount of blood drawn during the approximately 16 weeks of participation in the study is less than 500 ml, which is the standard amount of blood drawn at a single donation of blood from a blood donor. The use of intravenous cannula can cause irritation or infection of vein or insertion site. All procedures will be performed as described in SOP.