Bone quality deteriorates in mice with pulmonary emphysema despite preserved open-field-assessed spontaneous locomotor activity.

Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of fracture; however, the mechanisms underlying skeletal fragility in COPD remain incompletely understood. In particular, it is unclear whether bone deterioration is primarily attributable to physical inactivity or to intrinsic disease-related factors. In this study, we investigated the effects of emphysema on bone quality under conditions of comparable open-field-assessed spontaneous locomotor activity in an elastase-induced emphysema mouse model. Open-field-assessed spontaneous locomotor activity, feed intake, water intake, urine volume, and fecal volume did not differ between emphysema and control mice. In contrast, mice with emphysema exhibited impaired bone formation, deterioration of trabecular bone microstructure, and reduced bone material properties, including altered apatite c-axis orientation, the accumulation of advanced glycation end products, and increased bone brittleness. Exploratory cap analysis of gene expression sequencing of pooled bone marrow samples provided hypothesis-generating signals implicating mitochondrial and oxidative stress-related pathways. These results suggest that emphysema is associated with skeletal deterioration despite comparable open-field-assessed spontaneous locomotor activity and provide new insight into the mechanisms underlying fracture risk beyond bone mineral density in patients with chronic lung disease.