The accurate screening of osteoporosis is important for identifying persons at risk. The diagnosis of bone conditions using dual X-ray absorptiometry is limited to extracting areal bone mineral density (BMD) and fails to provide any structural information. Computed tomography (CT) is excellent for morphological imaging but not ideal for material quantification. Advanced photon-counting detector CT (PCD-CT) possesses high spectral sensitivity and material decomposition capabilities to simultaneously determine qualitative and quantitative information. In this study, we explored the diagnostic utility of PCD-CT to provide high-resolution 3-D imaging of bone microarchitecture and composition for the sensitive diagnosis of bone in untreated and ovariectomized rats. PCD-CT accurately decomposed the calcium content within hydroxyapatite phantoms (r = 0.99). MicroCT analysis of tibial bone revealed significant differences in the morphological parameters between the untreated and ovariectomized samples. However, differences in the structural parameters of the mandible between the treatment groups were not observed. BMD determined with microCT and calcium concentration decomposed using PCD-CT differed significantly between the treatment groups in both the tibia and mandible. Quantitative analysis with PCD-CT is sensitive in determining the distribution of calcium and water components in bone and may have utility in the screening and diagnosis of bone conditions such as osteoporosis.