Solid-State Nuclear Magnetic Resonance Identifies Abnormal Calcium Phosphate Formation in Diseased Bones.

The crystallites of calcium phosphate (CaP) in bones consist of hydroxyl apatite (HA) and amorphous calcium phosphate (ACP). These nanoscale structures of CaP are sculptured by biological bone formation and resorption processes and are one of the crucial factors that determine the overall strength of the constructs. We used one- and two-dimensional 1H-31P solid-state nuclear magnetic resonance (SSNMR) to investigate the nanoscopic structural changes of CaP. Two quantitative measurables are deduced based on the heterogeneous linewidth of 31P signal and the ratio of ACP to HA, which characterize the mineral crystallinity and the relative proportion of ACP, respectively. We analyzed bones from different murine models of osteopetrosis and osteoporosis and from human samples with osteoporosis and osteoarthritis. It shows that the ACP content increases notably in osteopetrotic bones that are characterized by defective osteoclastic resorption, whereas the overall crystallinity increases in osteoporotic bones that are marked by overactive osteoclastic resorption. Similar pathological characteristics are observed for the sclerotic bones of late-stage osteoarthritis, as compared to those of the osteopetrotic bones. These findings suggest that osteoclast-related bone diseases not only alter the bone density macroscopically but also lead to abnormal formation of CaP crystallites. The quantitative measurement by SSNMR provides a unique perspective on the pathology of bone diseases at the nanoscopic level.