New research from Texas Biomedical Research Institute, which was recently published in Journal of Bone and Mineral Research, suggests that structural bone geometry in osteoporotic patients may predispose certain individuals for atypical fractures, and quantitative computed tomography (QCT) might be a more powerful diagnostic than the current gold-standard bone mineral density (BMD) and dual-energy X-ray absorptiometry (DXA) tests. Texas Biomedical’s Lorena M. Havill, PhD, and researchers from the Southwest Research Institute and Indiana University were unsatisfied by the fact that BMD measurements are insensitive in predicting patients’ risks for fractures, especially in the populations of menopausal women and older adults who have low bone strength. The lack of a reliable predictor has led to a clinical problem that costs nearly $17 billion in the United States and a death rate of 24% within the first year of experiencing a hip fracture due to weak bones.
Instead of relying on BMD measurements, Havill and the research team created a statistical shape and density modeling (SSDM) method to predict the risk of fracture of long bones. Using baseline QCT images of a group of men older than 65 years of age in the Osteoporotic Fractures in Men Study, the researchers determined the spatial geometry and hydroxyapatite distribution of patient femurs. BMD was also determined to be used as a comparator. Patients were questioned every four months about suffering a fracture, and the responses were used to compile a regression model comparing risk of fracture to factors such as age and bone geometry.
The resulting SSDM-based prediction model was able to correctly identify 55% of fracture cases and 94.7% of non-cases when adjusted for age. Patient BMD was able to correctly identify only 10% of fracture cases and 91.3% of non-cases. The authors attributed the success of the SSDM-based model to its ability to detect subtle structural changes in bone.
A large part of bone’s structure is determined by genetics, although some of it is influenced by its daily stress loads (as described by Wolff’s Law: “form follows function”). In a study published in 2013 by Havill and colleagues in ILAR Journal, research used baboons to determine the genetic factors that influence features of osteoporosis. Laboratory baboons were used because their environmental stimuli can be completely controlled, allowing their genetic variations to be isolated as the influencing variable of bone structure. Additionally, according to Dr. Havill, “Baboons are anatomically and physiologically very similar to humans, and these animals live a long time, so they develop many of the same age-related diseases that we do. This makes them a good model for age-related diseases such as osteoporosis.”
By studying 101 baboons from a pedigreed colony at Southwest National Primate Research Center, the researchers identified that bone remodeling dynamics resulting from inherited differences led to altered microstructure. “The results of this study suggest an explanation for why some women respond differently to the widely prescribed bisphosphonates,” said Dr. Havill. These findings may be used to further identify patients at high risk for atypical femoral fractures.