UVA develops a ‘Google earth’ view of bone — with an eye toward disease prevention

Everyone knows that that we can view the broad structures of our bones in the body by taking X-rays. Yet that’s just scratching the surface. Science now has a host of new imaging and characterization techniques to go deeper, and define more narrowly, the architecture and relative health of our bones at the micro-, nano- and sub-nanometer dimensions.

So many tools, in fact, that a University of Virginia mechanical engineer interested in injury biomechanics and the tissue architecture underlying various skeletal conditions wanted to find the ideal way to combine the usefulness of this latest technology.

In a new paper published this month in Nature: Scientific Reports, UVA Engineering and Applied Science assistant professor Toni Tang outlines an ideal workflow for combining the latest advanced imaging and characterization technology that could result in an improved fundamental understanding of porous bone, which could inform the detection of diseases.

This is the first time the bone structure has been rendered in 3D across all of its relevant measures.

“The main breakthrough of this study is the establishment of a correlative workflow that can be used to examine a biological tissue across many length scales from millimeter to nanometer, all in 3D, and within exactly the same tissue volume,” Tang said. “This is the first time the bone structure has been rendered in 3D across all of its relevant measures.”

She compared her methodology to the concept of Google Earth; do you want the view from 280 miles above, or a street-grid or ground-level view? 

The Bones of the Study

For the study, Tang and teams of researchers in Canada and California, sought to know more about human trabecular bone. 

Because this type of bone, also known as cancellous, isn’t solid throughout, it is held together by a series of rods and plates that help absorb shock, for example. 

Trabecular bone structures can be found at the ends of long bones such as the femur, or thigh bone, which connects the hip flexor muscles. An adult subject with no known bone health issues consented to donate a femur sample for Tang’s research.

The unique trabecular architecture also contributes to the strength of the vertebrae in the spine, reinforces the skull’s protective casing and helps shield portions of the hip bones from fracture.

The team used a femtosecond laser, which emits short, quick pulses of light, to produce a precise grid. The grid allowed the researchers to make correlations between imaging methods and the identification of structures of interest. Methods of imaging included ion beam-scanning electron microscopy, which is surface focused, and X-ray microscopy, which penetrates deep into a sample.

Right now, Tang is interested in the general benefits of the bone research. With better analysis, she said, will come better scientific theories and means of predicting the progression of bone diseases. 

“This new process can hopefully help examine biological tissue structure from a fundamental perspective,” she said. “For example, in many bone diseases, the structure changes occur across all scales — at the collagen and mineral level, but also at microscale bone units level, as well as the whole bone level.”

Potential Future Applications

Tang’s collaborative research may one day help take medicine beyond its current, less precise methodologies. Assessing the risk of hip fractures could be one such application.  

A trabecular bone score, referred to as TBS for short, is often generated by doctors on postmenopausal women and men over 50 to determine bone health and risk of injury. The score is derived by imaging the spine in the lower back then applying a computer algorithm. Tang’s workflow might better detect emergent patterns at the nanoscale, such as early signs of osteoarthritis.

“Early stages of osteoarthritis have subtle structural changes that aren’t detectable by clinical tools,” she said. “This new workflow might be utilized, for example, to identify those small changes and help understand the etiology of osteoarthritis.” 

Still, she emphasizes that there is much more work to be done to know if her workflow, or some variation on it, might translate well to a medical lab setting.

Tang said she also thinks the increased understanding of how trabecular bone’s complex hierarchical structure contributes to resilience in a healthy body might mean her workflow could contribute to the field of bioinspired materials. 

The same goes for other biological tissues and even non-biological materials that can be analyzed with her method, she added — everything from semiconductor devices to geological specimens. 

Tang’s lab, at UVA Engineering’s Center for Applied Biomechanics, collaborated on the research with labs at the Canadian Centre for Electron Microscopy at McMaster University in Hamilton, Canada, the Bharti School of Engineering and Computer Science at Laurentian University in Sudbury, Canada, and the Department of Preventive and Restorative Dental Sciences at the University of California.