When used to treat osteoporosis, no more than 2 years of parathyroid hormone (PTH) is permitted, raising the question of whether antiresorptive therapy should be given after PTH is discontinued. This prospective, randomized, double-blind trial, the Parathyroid Hormone and Alendronate (PaTH) study, compared full-length PTH (1-84), alendronate, and the combination. The goal was to learn whether antiresorptive treatment is necessary to maintain the gain in bone mineral density (BMD) achieved after a year of PTH (1-84) treatment. The study population included 238 postmenopausal women 55 to 85 years of age who had a T score for BMD below -2.5 at the femoral neck, total hip, or spine (or a T score below -2) combined with other risk factors such as a history of fracture. Participants were randomly assigned to 1 year of PTH followed by 1 year of alendronate; PTH followed by placebo; PTH plus alendronate in the first year and alendronate in year 2; or alendronate for 2 years. Full-length PTH (1-84) was given in a dose of 100 μg daily and alendronate in an oral dose of 10 mg daily. Full compliance with treatment was 75% and 82% in the first and second years, respectively. BMD at the lumbar spine increased significantly in all treatment groups over 2 years, most markedly (12.1%) in the PTH-alendronate group and least (4.1%) in the PTH-placebo patients. The increase in BMD in the combination-alendronate and 2-year alendronate groups was significantly greater than in the PTH-placebo group but smaller than in the PTH-alendronate group. The PTH-alendronate patients had a significantly greater increase in BMD at the femoral neck and total hip over 2 years than women in the PTH-placebo group, but a significant loss at the distal radius was found in of both these groups. Women in all treatment groups-but especially the PTH-alendronate group-gained volumetric BMD in trabecular bone during the 2-year study. In the second year, women in the PTH-alendronate group gained significant BMD at the spine (4.9%) and hip (3.6%). At the same time, women in the PTH-placebo group lost significant BMD at the spine. The 21 women having clinical fractures during the 2-year study represented 8.8% of the total; there were no major differences between treatment groups. Women taking alendronate rather than placebo in year 2 were not at higher risk of adverse events. Any increase in BMD after a year of PTH treatment is rapidly lost afterward, but this is not the case if the bisphosphonate alendronate is administered for a further 12 months. There was no evidence from this study that combining PTH with alendronate is more effective than giving either agent by itself.