A total of 113 postmenopausal women (69 controls, 33 using hormone replacement therapy (HRT), and 11 using bisphosphonate) were evaluated twice over 2 years with a new noninvasive, radiogrammetry-based technique called digital X-ray radiogrammetry (DXR) and conventional bone densitometry of the spine, hip, and forearm. Longitudinal changes in bone densitometry were compared with changes captured by DXR: BMD evaluated by DXR (BMDDXR), cortical thickness of the second metacarpal (CTMC2), and porosity of cortical bone. The expected annual postmenopausal reduction in BMD in the control group was detected by BMDspine (-0.8%, P < 0.01), BMDhip (-1.6%, P < 0.001), BMDforearm (-1.5%, P < 0.001), DXR-BMD (-0.8%, P < 0.001), and CTMC2 (-1.1%, P < 0.001). In the HRT group, smaller reductions were seen in BMDDXA, but only significant at the hip (-1.0%, P < 0.01) and distal forearm (-1.0%, P < 0.02). In the bisphosphonate group, cortical porosity was significantly reduced (P < 0.025). Comparing longitudinal changes in age-matched subsamples of controls and bisphosphonate treated, BMDDXR, CTMC2, and porosity of cortical bone all differed significantly (P < 0.01, P < 0.05, P < 0.05, respectively), whereas the BMDDXA measurements did not. In conclusion, DXR provides a densitometry equivalent measurement of the distal forearm and hand and seems to offer new information on the porosity of cortical bone. This may prove useful in the evaluation of bone loss and offer new insight into the effects of different antiresorptive treatment regimens used in the prevention of osteoporosis.