Background: Identifying postmenopausal women with a high risk of having osteoporosis and fractures is a current challenge. This study aimed to assess the diagnostic performance of biochemical tests in identifying secondary osteoporosis and the fracture risk assessment tool (FRAX) in identifying fracture risk. Methods: Data from biochemical tests and bone densitometry of postmenopausal women were analyzed. Additionally, the FRAX result was obtained and the patients were classified according to the National Osteoporosis Guideline Group (NOGG). Results: A total of 646 women were evaluated, of whom 201 (31.1%) had osteoporosis or a previous frailty fracture. These women had statistically different parathyroid hormone (PTH) and alkaline phosphatase serum levels (p<0.01 and p=0.02, respectively) than those without osteoporosis or fracture. However, those at high risk had a higher prevalence of hypovitaminosis D (46% vs. 36%) and hypocalciuria (17% vs. 9%). The FRAX showed an area under the curve of 0.757 (p<0.01) and 0.788 (p<0.01) for identifying women at risk for “major fractures” and “hip,” respectively. The NOGG categorization had a sensitivity of 19% to identify high-risk women, a specificity of 91.3% for low-risk women, with a positive predictive value of 57.4% and a negative predictive value of 64.6%. Conclusions The evaluation of PTH, 25-hydroxy-vitamin D, serum calcium, and 24-hr urinary calcium proved adequate for initial osteoporosis screening. The FRAX tool has a regular ability to screen women at risk for fracture, and the NOGG method has high specificity to identify those at low risk.