The efficacy of alendronate in slowing the loss of bone mass, or even in increasing it, in osteoporotic patients and thus reducing the risk of new fractures has been described. Nevertheless, the way of taking this drug, together with its side effects, sometimes produces withdrawals. In this study, we analyzed if an alternative way of taking the alendronate improves the follow-up of the treatment and if it had the same effect on bone mineral metabolism than the traditional way of prescription. An open, intention-to-treat study, with follow-up of 2 yr was conducted. Eighty women suffering from postmenopausal osteoporosis were included in the study. They were classified in a random manner into two groups, each one of them received 10 mg/d alendronate, together with 1.2 g of calcium and 800 IU of Vitamin D3. Group I received the drug fasting, before breakfast, as usually prescribed and group II received the alendronate fasting, at noon, before lunch. Biochemical markers of bone remodeling were determined. Total alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine calcium/creatinine ratio, crosslinked N-telopeptides of type I collagen/creatinine ratio, serum calcium, and parathyroid hormone were also determined, and a lateral dorsolumbar radiography of the spine was performed. Bone mineral density was determined in the lumbar spine by dual-energy X-ray absorptiometry and quantitative computed tomography and by dual-energy X-ray absorptiometry in the proximal femur. Both groups showed an increase in bone mineral density in the lumbar spine and in the proximal femur, which was statistically significant after 1 yr of treatment in the range between 1.5% and 4.3%, depending on the anatomical localization where bone mineral density was measured. There was also an important decrease in the biochemical markers of bone remodeling, between 5.6% and 42.5%, depending on the biochemical marker; the decrease of amino-terminal telopetide during the first year was more important. The group that received alendronate in the morning reported a significantly higher number of withdrawals than the group that received the drug at noon. The alternative administration of 10 mg alendronate at noon had the same effect on bone mineral metabolism than its traditional administration in the morning, but the rate of withdrawals was significantly lower.