Conversion of bone marrow blood vessels into bone leads to “microvascular dead space”: A potential etiology for bone and bone marrow disease with advancing age

Abstract

Age-related alterations in bone and bone marrow (i.e., lower mass, vascular dysfunction, reduced and centripetal blood flow, and marrow ischemia and adiposity) coincide with the ossification of bone marrow blood vessels. Diaphyseal bone marrow blood vessels from young (4-6 mon) and old (22-24 mon) male Fischer-344 rats and humans (n=3; 59-75 yrs.) were examined via transmitted light-, stereo-, scanning electron [SEM]- and transmission electron [TEM]-microscopy. Cortical bone fragments and bone marrow blood vessels from rats (n=3/4 per age group) were analyzed by Fourier Transform Infrared (FT-IR) spectroscopy. Femora were scanned by μCT for determination of ossified vessel volume in the diaphyseal marrow (n=5 per age group) and bone volume in the distal metaphysis (n=4 per age group). In a separate group of young (n=8) and old (n=8) male Fischer-344 rats, the circulatory system was perfused with a barium sulfate solution to visualize patent bone marrow blood vessels via histology. Subsequently, femoral sh...