Subclinical Emphysema Linked to Accelerated Bone Loss in Men Without COPD
CT and AI may help flag those at risk, prompt earlier intervention
Subclinical emphysema-like changes visible on chest CT scans may provide an early warning sign of accelerated vertebral bone loss in people without chronic obstructive pulmonary disease (COPD), according to a large, retrospective, multiethnic study published in Radiology. Over time, bone loss progressed fastest in men.
“Our group previously showed emphysema-like changes are associated with all-cause mortality in people with normal spirometry, and the fact they now predict both mortality and bone mineral density (BMD) loss suggests systemic vulnerability rather than isolated lung disease,” said Shadpour Demehri MD, senior author and professor of radiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine in Baltimore. “These changes may be an imaging marker of systemic processes affecting multiple organs, though this remains an evolving research area.”
Takeshi Fukuda, MD, PhD, assistant professor, Department of Radiology, The Jikei University School of Medicine, Tokyo, and author of a related Radiology commentary on the topic agrees.
“The role of radiology is expanding from detecting established disease to identifying early imaging signatures of disease,” he said. “I believe opportunistic imaging is likely to become one of the most rapidly evolving areas in radiology as AI-enabled quantitative image analysis becomes increasingly feasible.”
Extracting More From Routine CT
To explore the relationship between emphysema-like changes and bone health, the researchers used AI tools to generate quantitative measurements from routine chest CT scans.
One deep learning model quantified the percentage of emphysema-like changes in the lungs at baseline. A second model extracted vertebral BMD measurements from the same CT scans.
Unlike the binary gold-standard T-score classification used to diagnose osteoporosis, these CT-based measures provided continuous biological data that could capture more subtle changes over time.
“T-scores depend on the reference population,” Dr. Fukuda said. “Continuous biomarkers excel at longitudinal monitoring, detecting subtle changes before diagnostic thresholds are crossed. They also may evaluate trabecular microarchitecture, an important determinant of bone quality.”
He added that optimal future imaging should evaluate both bone density and quality to better predict fracture risk.
The study included a cross-sectional analysis of 2,312 participants (median age 67) and a longitudinal subset of 1,109 participants (median age 65). These participants were drawn from the Multi-Ethnic Study of Atherosclerosis (MESA), a large, diverse U.S. cohort of adults without diagnosed cardiovascular disease at baseline who have been followed prospectively for decades.
Across the cohort, higher percentages of emphysema on CT were associated with lower bone density at baseline.
Among the 1,109 participants who received follow-up CTs approximately six to eight years later, higher emphysema was associated with accelerated vertebral bone loss, a finding that was significant in men but not women. Nearly four in 10 (39%) men in the study had emphysema above the identified 2.7% threshold, beyond which the association with bone loss became statistically significant.
“The strength and consistency in men was striking: 0.38 mg/cm³ per year faster bone loss for each standard deviation increase in emphysema, persisting across every sensitivity analysis,” said Elena Ghotbi, MD, lead study author and postdoctoral research fellow, in Dr. Demehri’s research group at Johns Hopkins University School of Medicine. “Even after adjusting for spirometry, CT-derived emphysema remained associated with bone loss, suggesting it captures information beyond conventional pulmonary function tests.”
According to Dr. Ghotbi, Black/African American participants also showed a significant association over time between emphysema and accelerated vertebral bone loss (β = –0.24 mg/cm³ per year, P = .002), although this association was not observed after excluding participants with chronic respiratory symptoms.
“Even after adjusting for spirometry, CT-derived emphysema remained associated with bone loss, suggesting it captures information beyond conventional pulmonary function tests.”
— ELENA GHOTBI, MD
Use of Opportunistic CT and Personalized Assessment Likely to Rise
The researchers emphasize that if the findings are validated in additional cohorts, structured emphysema reporting could complement existing risk stratification strategies and preventive interventions.
“Quantifying emphysema-like changes could serve as an opportunistic biomarker, meaning we could extract additional health information from scans already being done, without additional radiation exposure or cost to patients,” Dr. Demehri said. “The value would be in catching risk earlier, before fractures occur, as they carry significant morbidity, mortality and healthcare costs.”
As adoption of photon-counting CT (PCCT) and AI continues to increase, Dr. Fukuda expects the use of opportunistic imaging will as well.
“PCCT can provide higher-resolution imaging at lower radiation doses, and AI can extract subtle quantitative information from large imaging datasets that may not be readily recognized by human readers,” he said. “However, I suspect that a single universal threshold will not always be appropriate for every population. Future risk prediction models may need to incorporate population-specific factors and move toward more personalized assessment rather than relying on uniform cutoff values.”
For More Information
Access the Radiology article, “CT Emphysema and Deep Learning-derived Vertebral Bone Loss in Individuals without COPD: Findings from MESA,” and the related commentary, “Revealing the Lung-Bone Axis with Opportunistic CT: The Expanding Role of Radiology.”
Read previous RSNA News stories on opportunistic imaging: