Background. Prolonged immobilization, nutritional and vitamin D deficiency, and specific drug administration may lead to significant bone resorption. Methods and Patients. We prospectively evaluated critically ill patients admitted to the ICU for at least 10 days. Demographics, APACHE II, SOFA scores, length of stay (LOS), and drug administration were recorded. Blood collections were performed at baseline and on a weekly basis for five consecutive weeks. Serum levels of PINP, β-CTx, iPTH, and 25(OH)vitamin D were measured at each time-point. Results. We enrolled 28 patients of mean age 67.4 ± 2.3 years, mean APACHE II 22.2 ± 0.9, SOFA 10.1 ± 0.6, and LOS 31.6 ± 5.7 days. Nineteen patients were receiving low molecular weight heparin, 17 nor-epinephrine and low dose hydrocortisone, 18 transfusions, and 3 phenytoin. 25(OH)vitamin D serum levels were very low in all patients at all time-points; iPTH serum levels were increased at baseline tending to normalize on 5th week; β-CTx serum levels were significantly increased compared to baseline on 2nd week (peak values), whereas PINP levels were increased significantly after the 4th week. Conclusions. Our data show that critically ill patients had a pattern of hypovitaminosis D, increased iPTH, hypocalcaemia, and BTMs compatible with altered bone metabolism.