Overview
Obesity has emerged as a risk factor in the onset of bone, muscle and adipose tissue impairments that are further aggravated by vitamin D deficiency. A link of an active bone-muscle-adipose axis is represented by Wnt pathway. This study will test the hypothesis that vitamin D improves bone, muscle, and adipose tissue health through a positive modulation of Wnt pathway. It will be carried out a double-blind, placebo-controlled study of cholecalciferol supplementation in vitamin D-deficient obese adults. Specific aims will be: 1) to test the direct effect of vitamin D on Wnt signaling in bone, muscle, and adipose tissue; 2) to evaluate muscle mass and strength; 3) to assess changes in vitamin D status across different administration strategy (weekly, fortnightly, monthly).
This study will provide not only insight of new mechanisms involved in the pathophysiology of obesity-related musculoskeletal impairments but also evidence for new treatment recommendations for vitamin D deficiency in obesity.
Eligibility
Inclusion Criteria:
- Ambulatory willing and able to provide informed consent;
- post-menopausal women (55-75 y.o.) and age-matched men;
- BMI 30 >= kg/m2;
- serum 25OHD < 20 ng/ml
- hip replacement surgery due to osteoarthritis according to orthopedic clinical decision
Exclusion Criteria:
- eGFR <40 ml/min/1.72 m2 by EPI formula (21);
- hypercalcemia (>10.5 mg/dL);
- osteoporosis (hip or vertebral t-score >-2.5);
- conditions affecting bone
- vitamin D and/or calcium metabolism (chronic liver disease, renal failure, malabsorption, hypercortisolism);
- medications altering bone metabolism (e.g. denosumab, bisphosphonates, teriparatide, glucocorticoids, aromatase inhibitors, estrogen);
- enrollment in an interventional clinical trial in the previous 3 months.