Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone
1Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE 19713, USA.
Insights
Bone marrow blood vessels ossify with age in rats and humans, leading to reduced blood flow and potential implications for elderly bone health.
Area of Science:
- Bone Biology
- Vascular Biology
- Gerontology
Background:
- Bone microvascular calcification is a poorly understood phenomenon.
- Age-related changes in bone marrow vasculature may impact bone health.
Purpose of the Study:
- To characterize bone microvascular ossification in aging rats.
- To investigate the relationship between ossification, patent vessels, and adipocytes.
- To confirm ossified vessels in human vascular disease patients.
Main Methods:
- Barium sulfate perfusion for patent vessel visualization in rat femora.
- Bone histomorphometry for quantifying ossified and calcified vessels.
- Microcomputed tomography (μCT) for microvascular ossification quantification.
- Microscopic examination of isolated bone marrow blood vessels from rats and humans.
Main Results:
- Significant increase in ossified vessel volume (4800%) in old versus young rats.
- Elevated calcified and ossified vessel volumes per tissue volume with age.
- Increased adipocyte volume per patent vessel volume in older rats.
- Presence of osteocyte lacunae on ossified vessels, indicating transition to bone.
Conclusions:
- This is the first study to report bone marrow blood vessel ossification in rats and humans.
- Vessel ossification creates "microvascular dead space," impairing patency and vasomotor function.
- Bone microvascular ossification may be a key factor in age-related bone and bone marrow changes.
- Clinical implications include potential challenges in treating bone diseases in the elderly.
Abstract:
Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p<0.05) in the old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p<0.05) 262%, 375% and 263%, respectively, in the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in "microvascular dead space" in regard to loss of patency and vasomotor function as opposed to necrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly.
Related Concept Videos
01:29Blood and Nerve Supply to the Bones
Nutrient Artery
The nutrient artery is the main blood vessel that enters the diaphysis via the nutrient foramen. While most long bones have only one nutrient foramen, large bones, such as the femur, may have two. This...
01:23Bone as Supporting Connective Tissue
Bone Matrix
Bone, or osseous tissue, is a connective tissue that has a large amount of two different types of matrix material. The organic matrix is similar to the matrix material found in other connective tissues, including some amount of collagen and elastic fibers. This gives strength and flexibility to the tissue. The inorganic matrix consists of mineral salts— mostly calcium salts—...
01:09Spongy Bone
Spongy bone is more porous, and less dense compared to compact bone. It is composed of concentric lamellae that are arranged irregularly to form the trabecular network. In some bones, the spaces between trabeculae contain red marrow, where...
01:26Bone Markings
Articulating Projections
Articulating projections are found where two bones meet to form a joint. These structures are usually found at the ends of bones. The largest articulation is a rounded projection called the head, supported by a narrow neck at the ends of...