Skeleton and Bone Marrow

Damage to the skeleton, hematopoietic tissue of the bone marrow, and epithelial tissues closely apposed to the skeleton has been noted in animals administered 144Ce in relatively soluble forms by inhalation or injection. At relatively early times after exposure the major target organ has been the bone marrow while at later times all three tissues have shown effects of the radiation damage from the l44Ce deposited in the skeleton. 

Moskalev et al. (1966a 1966b) reported that rats injected with high levels of 144Ce citrate died with acute bone marrow damage at relatively 

Survival cf Boogie Dogs After inhoiotian of Ceds 

Potential ooDose-Lung900rads Liver2200rads-Sk eton 670rads 

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Nervous system Skeleton and bone marrow Thyroid... 

The skeleton is divided into cortical and trabecular regions, and each of these is subdivided into bone surfaces, bone volume, and bone marrow. Some 70% of the thorium reaching the blood is assigned initially to bone surfaces and is subsequently transferred to bone marrow by bone resorption, or to bone volume by bone formation. The removal half-time from bone marrow to blood is assumed to be 0.25 years, and is redistributed in the same pattern as the original input to blood. 

Mechanically, the bones that constitute the skeleton provide protection, support and a framework of levers which enable attached muscles to develop the forces that make locomotion possible. Within cavities in the long bones of the limbs is the bone marrow, where erythrocytes (red cells) and immune cells (white cells) are produced for the blood and lymph. Adipocytes are also present in the bone marrow indeed they oumumber the other cells (see Chapters 7 and 17). 

Production of blood cells in bone marrow of the central axial skeleton is referred to as medullary hematopoiesis. Hematopoietic tissue in adult bone marrow is well perfused and contains fat cells (adipocytes), and various types of blood and blood precursor cells encased within a protein matrix. Fibroblast, stromal and endothelial cells within bone marrow, serve as sources of matrix proteins as well as a factory for growth factors and chemokines that regulate blood cell production and release matured cells into the circulation [2,3]. Chemokines act as signal lamps for trafficking of lymphocytes in and out of lymphoid tissues. Erythroblasts, neutrophils, lymphoblasts, macrophages, megakaryocytes, and pluripotent stem cells are also found within the calcihed lattice crisscrossing the marrow space. 

Rehcular connective tissue this is a network of reticular fibers made from fine collagen, type 111. These fibers form a soft skeleton to support the lymphoid organs such as lymph nodes, bone marrow and spleen. 

The response of cells to radiotherapy also depends upon the rate of cell division, and the cell s physiological environment. Normal tissues that are characterized by a comparatively high rate of cell division (e.g., bone marrow, lymph nodes, gonads, intestinal mucous membrane, skin) have a high radiosensitivity. Among the most radiosensitive cancerous diseases are leukemia, malignant lymphoma (lymph-node cancer), Ewing s sarcoma (tumor of the skeleton), and myeloma. Even moderately radiosensitive tumors, e.g., cervical cancer in women, can often be treated successfully with radiotherapy alone. 

The bone Is composed of two distinct tissue structures cortical (compact) bone, and trabecular (cancellous) bone (3). Eighty percent of the skeleton is composed of cortical bone (e.g., long bones such as the humerus, radius, and ulna) (4,5), which is a relatively dense tissue (80-90% calcified) (4) that provides structure and support (3). Bone marrow cavities, flat bones, and the ends of long bones are all composed of trabecular bone, which Is considerably more porous (5-20% calcified) (4,5). To maintain healthy, well-mineralized bone, a continuous process of bone resorption (loss of ionic calcium from bone) and formation occurs along the bone surface. Cortical bone Is remodeled at the rate of 3% per year, whereas 25% of trabecular bone, which has considerably higher surface area, is remodeled annually (3). In terms of calcium turnover in bone, approximately 500 mg are removed and replaced on a daily basis. 

The percent of plutonium-239, administered by intravenous injection as the citrate or as the polymer, that distributed to the skeleton of dogs and mice was 2.8 to 3.1 % or 0.1 to 0.2%, respectively, after 6 days (Baxter et al. 1973). In rats 30 days after exposure to plutonium-239 as the citrate or as the polymer, 56.9 or 29.4%, respectively, distributed to the bone (Carritt et al. 1947). In dogs plutonium distribution in the skeleton was greatest to the trabecular or "spongy" bone and more was found in the red bone marrow, which is perfused with blood, compared with yellow or fatty bone marrow (Smith et al. 1984 Wronski et al. 1980). The rate of deposition in bone may be related to the rate of blood flow to bone, and in mice there appears to be a threshold rate for blood flow below which plutonium will not deposit to bone (Humphreys et al. 1982). 

Smith J, Miller S, Jee W. 1984. The relationship of bone marrow type and microvasculature to the microdistribution and local dosimetry of plutonium in the adult skeleton. Radiat Res 99 324- 335. 

Recurrent cervical cancer is associated with bone metastases (Fig. 7.39) in 15%-29% of patients at autopsy [ too, 103]. Typical locations are the bony pelvis as well as the lumbar and other vertebral bodies. Bone metastases in the ribs and extremities are less common. Skeletal metastases typically have an osteolytic character and originate from locally advanced or recurrent tumor in the pelvic sidewall or arise through retrograde tumor spread in patients with para-aor-tic lymph node metastasis [104]. Hematogenous dissemination to the skeleton occurs late. MRl with unenhanced and contrast-enhanced fat-saturated Tl-weighted sequences depicts bone metastases as hyperintense lesions in the low-intensity bone marrow with a high sensitivity. CT primarily shows the extent of osseous destruction. 

These requirements derive from the bone complex structure and properties. Bone is a complex and dynamic living tissue, which from morphological point of view can be divided into two types cortical or compact bone and trabecular or cancellous or spongy bone. The mass of the skeleton is composed of 80% compact bones and 20% spongy bones. Cortical and trabecular bones contain the same cells and extracellular matrix (ECM) components, except that they are organized in a different way. The trabecular bone consists of a porous matrix with intercormected columns filled with bone marrow and is being responsible for metabolic functions of the bone, while the cortical bone contains fewer spaces, forms the external layer of all bones and provides them protection and load-bearing capabilities (Baron, 2003, as cited in Wilson, 2011). 

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