JHrebicek / shutterstock.com
Can principles from engineering provide a broader understanding of how the human skeleton works and be used to help prevent a common and often consequential event for people as they age—bone fractures?
Research from a team of investigators that includes orthopedic surgeons and mechanical engineers suggests that, yes, looking at how engineered materials, such as metals and ceramics, function over time can illuminate how bones behave as a person ages.
In particular, the research focuses on fatigue as the missing link between bone fragility and fracture as aptly stated in the title of a recent study, “Fatigue as the Missing Link Between Bone Fragility and Fracture.”1 Fatigue, used in terms of fracture mechanics, implies that a material’s mechanical resistance will decrease over time as a result of repetitive, or cyclic, loading. Fatigue failure refers to the number of cycles, or the time needed, for the material to be damaged via crack growths that cause the material failure.
Applying this to the human skeleton, the investigators propose that some bone fractures in older people are the result of cyclic loading, producing microcracks that, over time, result in fatigue fracture. Older people are more susceptible to this type of fracture because of the well-known fact that bone remodeling and repair slows with age, but also, the investigators suggest, because the quality of bone in older people is decreased, evidenced by the decreased capacity of bone to handle weight-bearing loads.
Dr. Acevedo
“Most people think the elderly break a bone because they fall,” says lead author of the study Claire Acevedo, PhD, assistant professor, Department of Mechanical Engineering, University of Utah, Salt Lake City. The research, she says, suggests the “bone is already damaged by microcracks before they fall, so the fall may occur on an already partly broken bone or the fall may even be induced because the bone breaks at some point.”
New Insight into Skeleton Pathology
Calling the research fascinating, Thomas Parker Vail, MD, James L. Young Professor and chairman, Department of Orthopaedic Surgery, University of California, San Francisco, says it represents a new look at how bone responds and communicates within its own structure, as well as outside that structure.
Through imaging, he says the investigators have shown the tiny canals that connect osteocytes within the bone. If you overlay this imaging on images of neuronal networks, he says, the similarity is astounding.
“We don’t think of bone in the way we think of the brain, so intricately connected with cellular communication,” he says. “But in reality, what the research is beginning to show us with this connection between cells is the idea that the osteocyte, that particular cell that is most plentiful within the bone, may be the regulator of osteoclasts and osteoblasts.”
Identifying how cells within bones communicate is important for expanding prevention and treatment options beyond the use of current therapies, such as bisphosphonates, that only target the cells responsible for bone removal.
By identifying cyclic loading of weight-bearing bones as a mechanism of fracture due to the damage of microcracks over time, the research points to the importance of developing therapies that will also target cells in the bone responsible for bone quality—or those cells that help bones withstand loading or stress.
“It is now recognized that osteocyte cells are playing a bigger role than we thought,” says Dr. Acevedo.
Dr. Vail
For Dr. Vail, this broader understanding of the mechanisms of skeletal pathology is getting at what he says is the core of the problem—how to identify patients at risk of fracture and prevent an additional fracture in people after a fracture. “It is my sense that there are other opportunities to enhance a healthy skeleton more than we currently know about how the skeleton repairs itself and communicates with itself,” he says.
The current research points to a plausible new way to look at fracture risk and subsequently expanding thinking on potential new targets for treatment.
Arvind Nana, MD, an orthopedic surgeon in Fort Worth, Texas, however, questions the plausibility of fractures caused by microcracks in aging bones that over time weaken the bone and make it susceptible to fracture. Saying that such fragility fractures do seem plausible in compression fractures of the spine, he does not think these types of microcracks are commonly seen in hip fracture.
“If cyclic loading is the cause of a fracture, it most likely would be in the spine,” he says, adding that most hip fractures he sees are due to falls and rarely occur in people who say their hip just gave out.
Although Dr. Nana is primarily a trauma orthopedic surgeon and, therefore, sees patients who have fracture due to trauma, but as medical director of a geriatric hip fracture program in Fort Worth, he also sees a large number of hip fractures in older patients.
He and his colleagues are always looking for new information on bone fractures in older patients. One area of research from the study he thinks reasonable to pursue is to potentially target cells involved in bone repair and quality. “It may be important to look at different cells to target therapeutically,” he says. “Current medications primarily look at minimizing the rate of turnover of cells as opposed to looking at the cells that actually do the repair.”
Look to the Future
Emphasizing the prospective nature of the study, Dr. Acevedo says more research is needed to better understand the role of osteocytes to repair damaged bone. Also needed are better ways to identify which patients may be at fracture risk because of microcracks. Although imaging is useful, she says it is not sufficient to detect very small cracks. The only common symptom currently indicative of a patient with microcracks is pain.
She says pain in an elderly patient may be a sign of someone at risk of fracture. “This study tries to make clinicians aware that stress fracture can occur in the elderly under daily activities,” she says.
For Dr. Vail the research points to new avenues for prevention and treatment of skeletal pathologies that lead to fracture. Citing the great advances that have revolutionized the treatment of inflammatory arthritis with the use of tumor necrosis factor (TNF) inhibitors, he says he is “hopeful that these processes of identifying and understanding microtrauma of aging would provide avenues for similar breakthroughs of medical treatment of skeletal pathologies.”
Mary Beth Nierengarten is a freelance medical journalist based in Minneapolis.
Reference
- Acevedo C, Stadelmann VA, Pioletti DP, et al. Fatigue as the missing link between bone fragility and fracture. Nat Biomed Eng. 2018;2(2):62–71.
