Microstructural Assessment of Idiopathic Osteoporosis (IOP)

Bone is a complex biological material and to maintain its structural integrity, the organ continuously remodels itself. This process is guided by the osteocytes, which are the embedded cells that orchestrate tissue formation and resorption. This remodeling process is delicate and when compromised, bone is at risk for metabolic diseases to manifest — leading to fragile bone and, ultimately, fractures.

Idiopathic osteoporosis (IOP) is an infrequent type of osteoporosis that manifests as an early form of the disease in young adults. IOP is categorized as a rare bone disease, and the current understanding of it is limited. The goal of this project is to investigate the microstructure of bone biopsies from IOP patients and to determine specific biomarkers that can be used to differentiate between healthy and disease cases.

An ideal biomarker within the bone microstructure is the lacuna, which is the cave-like architecture that encloses the osteocyte. Osteocyte signaling is influenced by its mechanical environment, and therefore the surrounding lacuna will likely also be important. If lacunar geometry is distorted, the osteocyte’s mechanical environment will also be altered. Consequently, the ensconced osteocyte will experience an incorrect measure of its local mechanical environment, ultimately affecting patterns of tissue formation and resorption.

To investigate this hypothesis, lacunar biomarkers must be examined both morphologically and mechanically. Lacunar morphology is measured using micro-computed tomography (micro-CT) at a resolution of 1.2 micrometers. This generates an enormous amount of data (millions of lacunae) and is analyzed using a custom Python script. Micro-finite element (micro-FE) analyses are performed on sub-regions of imaged biopsies to simulate the lacunar mechanical environment. Together, the lacunar morphological biomarkers from the micro-CT analysis and the lacunar mechanical biomarkers from the micro-FE analysis provide a unique set of characteristics which, we hypothesize, will allow for the differentiation between healthy and IOP patients.