The ISCD recommends that bone mineral density (BMD) be monitored in patients undergoing antiresorptive therapy to identify patients with a significant BMD loss. This analysis compares the proportions of postmenopausal women treated with raloxifene 60 mg/d (n=82) or alendronate 10 mg/d (n=83) who had significant BMD loss in a randomized, double-blind, placebo-controlled trial that assessed changes in lumbar spine and femoral neck BMD from baseline to 1 yr, measured using dual-energy X-ray absorptiometry. According to ISCD criteria, significant BMD loss was defined as greater than the least significant change, calculated as precision multiplied by 2.77 (95% confidence interval). Assuming a 1% precision at the lumbar spine, the proportions of women with a loss of BMD greater than the least significant change (3%) were similar (p>0.05) between the raloxifene (3%) and alendronate (2%) groups. Assuming 2% precision at the femoral neck, the proportions of women with a loss greater than the least significant change (6%) were similar (p>0.05) between the raloxifene (1%) and alendronate (2%) groups. In conclusion, similar proportions of women did not respond to raloxifene or alendronate therapy, as measured by changes in lumbar spine or femoral neck BMD, when precision error was taken into account.