Bone microstructure and material composition in endocrine disorders

© 2018 Dr. Thuy Dan Thuy VuIn the general population, fractures are a significant healthcare issue. However, fractures also complicate several endocrine disorders. The overall aim of my study was to investigate the changes in bone structure and material composition underlying bone fragility in a number of endocrine diseases such as type 1 and type 2 diabetes mellitus as well as patients with PTH excess and PTH deficiency. High-resolution peripheral quantitative computed tomography was used to acquire images of the distal radius and tibia in cases and controls. Bone structure was assessed by the standard analysis protocol from the manufacturers that uses a threshold base algorithm in the type 1 and type 2 diabetes studies. A non-threshold base algorithm was used to analyze bone structure and matrix mineral density in the PTH excess and PTH deficiency study. The main findings were that patients with type 1 diabetes had no significant deficits in cortical and trabecular bone relative to controls. Patients with T1DM had a tendency towards lower bone formation and bone resorption markers. Patients with type 2 diabetes had similar cortical morphology whereas trabecular bone was better maintained than controls. These results are consistent with higher BMD in the spine and hip as well as lower bone remodelling markers observed in diabetic patients. PTH excess is deleterious to both cortical and trabecular bone. In patients with untreated primary hyperparathyroidism (PHPT), the normal or high trabecular density reported in several studies is likely to be the result of inclusion of cortical remnants in the medullary compartment. In patients with untreated PHPT, there was a left shift of the void-matrix mineralization density distribution curve relative to controls due to increased cortical porosity. Cortical and trabecular deficits in untreated PHPT may not be completely reversible with surgical treatment. Patients with PTH deficiency due to secondary rather than primary hypoparathyroidism have better maintained cortical and trabecular bone relative to controls as well as higher matrix mineral density. Similar results were found in women and in men. There was a rightward shift of the void bone matrix mineralization distribution curve for patients with hypoparathyroidism relative to controls. In conclusion, patients with type 1 and type 2 diabetes may have underlying bone fragility predisposing to fractures, but my study failed to identify microstructural abnormalities. Further work is needed to determine whether abnormalities in the material properties of bone may account for the increased fracture risk seen in diabetes. Patients with PTH excess have deficits to both cortical and trabecular bone. The normal or high trabecular density reported in several studies is likely to be the result of inclusion of cortical remnants in the medullary compartment. Patients with PTH deficiency due to secondary hypoparathyroidism rather than primary hypoparathyroidism have better maintained cortical and trabecular bone morphology as well as higher matrix mineralization density relative to controls. Prospective studies are needed to see how these skeletal abnormalities affect bone strength and fracture risk