Despite the discussion on the optimal threshold of 25-hydroxyvitamin D serum level continues, there is now consensus on the fact that post-menopausal and elderly populations have inadequate Vitamin D serum levels worldwide. The adjustment of these levels is necessary to improve both bone and general health, as it is to optimize bone response to antiresortive treatments. It is recommended, as endorsed by international clinical guides, to use Vitamin D3, the physiological form of Vitamin D, in a dose range between 600-2000IU. It should be administered on a daily basis or on its weekly or monthly equivalents. In Spain, the use of calcidiol (25(OH)D3) at the same dose than Vitamin D3 is the most extended prescription, notwithstanding the available evidence stating that they are not equipotent. This may lead to over-dosage. In order to provide evidence on this circumstance, a convenience study was performed. Four groups of ten post-menopausal osteoporotic women each (average age 67), deficient in Vitamin D ((25(OH)D 37.5±10 nmol/L)) were enrolled. Each group followed a different treatment regimen: (G1) vitamin D3 20μg/day [800IU/day]; (G2) 25 (OH)D3 20μg/day; (G3) 25(OH)D3 266μg/week and (G4) 25(OH)D3 0.266mg every two weeks. 25(OH)D levels were measured for each group at 0, 6 and 12 months, with the following results: G1 (40.5±4.7;80.0±2; 86.2±23.7), G2 (37,2±4.2; 161±21.7;188.0±24.0), G3 (38±3.7;213.5±80.0; 233.0±81.2), G4 (39.5±4;164.5±41,7;210.5±22.2). These data reveal that both metabolites are not equipotent. Calcidiol is faster and 3-6 times more potent to obtain serum levels of 25(OH)D in the medium to long term. This circumstance must be assessed and included in the therapeutic prescription guides for Osteoporosis, since it should be of concern when planning and prescribing treatments to normalize serum levels of 25(OH)D3 and avoid potential adverse impacts.