Men with osteoporosis have been neglected in the past, and only a few therapeutic trials have been performed in men. The bisphosphonate, alendronate, has been widely used for the treatment of postmenopausal osteoporosis. This prospective, open label, active controlled, randomized clinical study com- pared the effects of oral alendronate (10 mg daily) and alfa- calcidol (1 g daily) on bone mineral density (BMD), safety, and tolerability in 134 males with primary established osteo- porosis. All men received supplemental calcium (500 mg dai- ly). After 2 yr, alfacalcidol-treated patients showed a mean 2.8% increase in lumbar spine BMD (P < 0.01) compared with a mean increase of 10.1% in men receiving alendronate (P < 0.001). The corresponding changes in femoral neck BMD were 2.2% and 5.2% for the alfacalcidol and alendronate groups, respectively (P 0.009). The incidence rates of patients with new vertebral fractures were 18.2% and 7.4% for the alfacal- cidol and alendronate groups, respectively (P 0.071). Both therapies were well tolerated. Thus, alendronate produced favorable effects on BMD con- sistent with the results from another study in male osteopo- rosis. The average increase rates were higher than with alfa- calcidol. Alendronate may be superior to alfacalcidol in the treatment of men with established primary osteoporosis. (J Clin Endocrinol Metab 86: 5252-5255, 2001)