The "PTH and Alendronate" or "PaTH" study compared the effects of PTH(1-84) and/or alendronate (ALN) in 238 postmenopausal, osteoporotic women. We performed finite element analysis on the QCT scans of 162 of these subjects to provide insight into femoral strength changes associated with these treatments and the relative roles of changes in the cortical and trabecular compartments on such strength changes. Patients were assigned to either PTH, ALN, or their combination (CMB) in year 1 and were switched to either ALN or placebo (PLB) treatment in year 2: PTH-PLB, PTH-ALN, CMB-ALN, and ALN-ALN (year 1-year 2) treatments. Femoral strength was simulated for a sideways fall using nonlinear finite element analysis of the quantitative CT exams. At year 1, the strength change from baseline was statistically significant for PTH (mean, 2.08%) and ALN (3.60%), and at year 2, significant changes were seen for the PTH-ALN (7.74%), CMB-ALN (4.18%), and ALN-ALN (4.83%) treatment groups but not for PTH-PLB (1.17%). Strength increases were primarily caused by changes in the trabecular density regardless of treatment group, but changes in cortical density and mass also played a significant role, the degree of which depended on treatment. For PTH treatment at year 1 and for ALN-ALN treatment at year 2, there were significant negative and positive strength effects, respectively, associated with a change in external bone geometry. Average changes in strength per treatment group were somewhat consistent with average changes in total hip areal BMD as measured by DXA, except for the PTH group at year 1. The relation between change in femoral strength and change in areal BMD was weak (r(2) = 0.14, pooled, year 2). We conclude that femoral strength changes with these various treatments were dominated by trabecular changes, and although changes in the cortical bone and overall bone geometry did contribute to femoral strength changes, the extent of these latter effects depended on the type of treatment.