The aim of the present clinical trial is to examine the effects of everolimus, resistance training, or their combination on bone and muscle health formation in elderly women aged 60-75 years. The main questions it aims to answer are: Can rapamycin's analog (Everolimus), resistance training, or their combination, enhance bone formation and muscle functions in elderly women compared to non-treatment controls. Participants will be randomized 1:1:1:1 to one of the following treatment regimens: * Oral everolimus 5 mg once a week. * Oral placebo once a week. * Oral everolimus 5 mg once a week plus resistance training RT 1 hour, 3 times weekly. * Oral placebo once a week plus resistance training RT 1 hour, 3 times weekly. During the study there will be a total of 5-7 visits, where the participants will undergo the following: * Blood samles * DXA-, HRpQCT- (only Odense Universitetshospital) and MRI-scans * Muscle- and bone biopsies * Quality of life questionnaires * Testing of muscle funtion * Metabolic studies of muscle and bone protein turnover using labelling with deuturated water
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
148
Everolimus 5 mg administered once weekly for 24 weeks
Placebo administered once weekly for 24 weeks
Resistance training 3 times a week for 24 weeks
Institute of Sports Medicine, Bispebjerg Hospital
Bispebjerg, Region Sjælland, Denmark
Department of Endocrinology, Odense University Hospital
Odense, Region Syddanmark, Denmark
P1NP
Percentage change in circulating levels of bone formation marker N-terminal fragment of procollagen type 1 (P1NP) at 24 weeks as compared with baseline
Time frame: From baseline to end of treatment at 24 weeks
Bone resorption markers
Change in bone resorption markers (C-terminal telopeptide of type 1 collagen (CTX) at baseline, 4, 12 and 24 weeks.
Time frame: From baseline to end of treatment 24 weeks
BMD
Lumbar spine (L1-4), and total hip and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at screening visit/baseline, and 24 weeks.
Time frame: From screening to end of treatment 24 weeks
Bone mass
Bone mass at the distal radius and tibia measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, and 24 weeks.
Time frame: From baseline to end of treatment 24 weeks
Bone microarchitecture
Bone microarchitecture at the distal radius and tibia measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, and 24 weeks.
Time frame: From baseline to end of treatment 24 weeks
Bone geometry
Bone geometry at the distal radius and tibia measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 24 weeks.
Time frame: From baseline to end of treatment (24 weeks)
Muscle Cross-Sectional Area
Muscle Cross-Sectional Area (CSA) measured by Magnetic Resonance Imaging (MRI) at baseline, 12, and 24 weeks.
Time frame: From baseline to end of treatment 24 weeks
Muscle assessment
Change in muscle strength for the lower extremities, measured using a isokinetic dynamometry at baseline, midway and week 24.
Time frame: From baseline to end of treatment 24 weeks
Metabolic health (test 1)
Body weight measured by a digital scale at baseline, 4, 12, and 24 weeks.
Time frame: From baseline to end of treatment 24 weeks
Quality of life quiestionaire
Quality of life (QoL)questionnaire SF-12 questionnaire (including mental QoL and physical QoL, and various health and possible side effects) at baseline and 24 weeks
Time frame: From baseline to end of treatment 24 weeks
Muscle function (power)
Muscle function (power) using the 30-second sit-to-stand test (RSS) at baseline, midway and week 24.
Time frame: From baseline to end of treatment 24 weeks.
Bone formation markers
P1NP at baseline, 4 and 12 and 24 weeks.
Time frame: From baseline to end of study 24 weeks
Metabolic health (test 2)
Total body fat percentage assessed by dual-energy X-ray absorptiometry (DXA), at screening and 24 weeks.
Time frame: From screening to end of treatment 24 weeks
Metabolic health (test 3)
Lipid parameters (LDL, HDL, Triglycerides, Cholesterol) at baseline, 4, 12, and 24 weeks
Time frame: From baseline to end of treatment 24 weeks
Metabolic Health (Test 4)
Total lean mass assessed by dual-energy X-ray absorptiometry (DXA) screening and baseline, and 24 weeks.
Time frame: From screening to end treatment
Metabolic health (test 5)
Bone mineral density assessed by dual-energy X-ray absorptiometry (DXA) at screening and 24 weeks.
Time frame: From screening to end of treatment 24 weeks
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