Bone Book 9 Pdf

[Florene Pothoven]

Abone is a rigid organ[1] that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, and enable mobility. Bones come in a variety of shapes and sizes and have complex internal and external structures.[2] They are lightweight yet strong and hard and serve multiple functions.

Bone tissue (osseous tissue), which is also called bone in the uncountable sense of that word, is hard tissue, a type of specialised connective tissue. It has a honeycomb-like matrix internally, which helps to give the bone rigidity. Bone tissue is made up of different types of bone cells. Osteoblasts and osteocytes are involved in the formation and mineralisation of bone; osteoclasts are involved in the resorption of bone tissue. Modified (flattened) osteoblasts become the lining cells that form a protective layer on the bone surface. The mineralised matrix of bone tissue has an organic component of mainly collagen called ossein and an inorganic component of bone mineral made up of various salts. Bone tissue is mineralized tissue of two types, cortical bone and cancellous bone. Other types of tissue found in bones include bone marrow, endosteum, periosteum, nerves, blood vessels and cartilage.

In the human body at birth, approximately 300 bones are present. Many of these fuse together during development, leaving a total of 206 separate bones in the adult, not counting numerous small sesamoid bones.[3][4] The largest bone in the body is the femur or thigh-bone, and the smallest is the stapes in the middle ear.

Bone is not uniformly solid, but consists of a flexible matrix (about 30%) and bound minerals (about 70%), which are intricately woven and continuously remodeled by a group of specialized bone cells. Their unique composition and design allows bones to be relatively hard and strong, while remaining lightweight.

Bone matrix is 90 to 95% composed of elastic collagen fibers, also known as ossein,[5] and the remainder is ground substance.[6] The elasticity of collagen improves fracture resistance.[7] The matrix is hardened by the binding of inorganic mineral salt, calcium phosphate, in a chemical arrangement known as bone mineral, a form of calcium apatite.[8][9] It is the mineralization that gives bones rigidity.

Bone is actively constructed and remodeled throughout life by special bone cells known as osteoblasts and osteoclasts. Within any single bone, the tissue is woven into two main patterns, known as cortical and cancellous bone, each with a different appearance and characteristics.

Cancellous bone or spongy bone,[12][11] also known as trabecular bone, is the internal tissue of the skeletal bone and is an open cell porous network that follows the material properties of biofoams.[13][14] Cancellous bone has a higher surface-area-to-volume ratio than cortical bone and it is less dense. This makes it weaker and more flexible. The greater surface area also makes it suitable for metabolic activities such as the exchange of calcium ions. Cancellous bone is typically found at the ends of long bones, near joints, and in the interior of vertebrae. Cancellous bone is highly vascular and often contains red bone marrow where hematopoiesis, the production of blood cells, occurs. The primary anatomical and functional unit of cancellous bone is the trabecula. The trabeculae are aligned towards the mechanical load distribution that a bone experiences within long bones such as the femur. As far as short bones are concerned, trabecular alignment has been studied in the vertebral pedicle.[15] Thin formations of osteoblasts covered in endosteum create an irregular network of spaces,[16] known as trabeculae. Within these spaces are bone marrow and hematopoietic stem cells that give rise to platelets, red blood cells and white blood cells.[16] Trabecular marrow is composed of a network of rod- and plate-like elements that make the overall organ lighter and allow room for blood vessels and marrow. Trabecular bone accounts for the remaining 20% of total bone mass but has nearly ten times the surface area of compact bone.[17]

The words cancellous and trabecular refer to the tiny lattice-shaped units (trabeculae) that form the tissue. It was first illustrated accurately in the engravings of Crisstomo Martinez.[18]

Bone marrow, also known as myeloid tissue in red bone marrow, can be found in almost any bone that holds cancellous tissue. In newborns, all such bones are filled exclusively with red marrow or hematopoietic marrow, but as the child ages the hematopoietic fraction decreases in quantity and the fatty/ yellow fraction called marrow adipose tissue (MAT) increases in quantity. In adults, red marrow is mostly found in the bone marrow of the femur, the ribs, the vertebrae and pelvic bones.[19]

Bone receives about 10% of cardiac output.[20] Blood enters the endosteum, flows through the marrow, and exits through small vessels in the cortex.[20] In humans, blood oxygen tension in bone marrow is about 6.6%, compared to about 12% in arterial blood, and 5% in venous and capillary blood.[20]

Bone is metabolically active tissue composed of several types of cells. These cells include osteoblasts, which are involved in the creation and mineralization of bone tissue, osteocytes, and osteoclasts, which are involved in the reabsorption of bone tissue. Osteoblasts and osteocytes are derived from osteoprogenitor cells, but osteoclasts are derived from the same cells that differentiate to form macrophages and monocytes.[21] Within the marrow of the bone there are also hematopoietic stem cells. These cells give rise to other cells, including white blood cells, red blood cells, and platelets.[22]

Osteoblasts are mononucleate bone-forming cells. They are located on the surface of osteon seams and make a protein mixture known as osteoid, which mineralizes to become bone.[23] The osteoid seam is a narrow region of a newly formed organic matrix, not yet mineralized, located on the surface of a bone. Osteoid is primarily composed of Type I collagen. Osteoblasts also manufacture hormones, such as prostaglandins, to act on the bone itself. The osteoblast creates and repairs new bone by actually building around itself. First, the osteoblast puts up collagen fibers. These collagen fibers are used as a framework for the osteoblasts' work. The osteoblast then deposits calcium phosphate which is hardened by hydroxide and bicarbonate ions. The brand-new bone created by the osteoblast is called osteoid.[24] Once the osteoblast is finished working it is actually trapped inside the bone once it hardens. When the osteoblast becomes trapped, it becomes known as an osteocyte. Other osteoblasts remain on the top of the new bone and are used to protect the underlying bone, these become known as bone lining cells.[25]

Osteoclasts are very large multinucleate cells that are responsible for the breakdown of bones by the process of bone resorption. New bone is then formed by the osteoblasts. Bone is constantly remodeled by the resorption of osteoclasts and created by osteoblasts.[21] Osteoclasts are large cells with multiple nuclei located on bone surfaces in what are called Howship's lacunae (or resorption pits). These lacunae are the result of surrounding bone tissue that has been reabsorbed.[27] Because the osteoclasts are derived from a monocyte stem-cell lineage, they are equipped with phagocytic-like mechanisms similar to circulating macrophages.[21] Osteoclasts mature and/or migrate to discrete bone surfaces. Upon arrival, active enzymes, such as tartrate-resistant acid phosphatase, are secreted against the mineral substrate.[citation needed] The reabsorption of bone by osteoclasts also plays a role in calcium homeostasis.[27]

Woven bone is produced when osteoblasts produce osteoid rapidly, which occurs initially in all fetal bones, but is later replaced by more resilient lamellar bone. In adults, woven bone is created after fractures or in Paget's disease. Woven bone is weaker, with a smaller number of randomly oriented collagen fibers, but forms quickly; it is for this appearance of the fibrous matrix that the bone is termed woven. It is soon replaced by lamellar bone, which is highly organized in concentric sheets with a much lower proportion of osteocytes to surrounding tissue. Lamellar bone, which makes its first appearance in humans in the fetus during the third trimester,[31] is stronger and filled with many collagen fibers parallel to other fibers in the same layer (these parallel columns are called osteons). In cross-section, the fibers run in opposite directions in alternating layers, much like in plywood, assisting in the bone's ability to resist torsion forces. After a fracture, woven bone forms initially and is gradually replaced by lamellar bone during a process known as "bony substitution". Compared to woven bone, lamellar bone formation takes place more slowly. The orderly deposition of collagen fibers restricts the formation of osteoid to about 1 to 2 μm per day. Lamellar bone also requires a relatively flat surface to lay the collagen fibers in parallel or concentric layers.[32]

The extracellular matrix of bone is laid down by osteoblasts, which secrete both collagen and ground substance. These cells synthesise collagen alpha polypetpide chains and then secrete collagen molecules. The collagen molecules associate with their neighbors and crosslink via lysyl oxidase to form collagen fibrils. At this stage, they are not yet mineralized, and this zone of unmineralized collagen fibrils is called "osteoid". Around and inside collagen fibrils calcium and phosphate eventually precipitate within days to weeks becoming then fully mineralized bone with an overall carbonate substituted hydroxyapatite inorganic phase.[33][29]

In order to mineralise the bone, the osteoblasts secrete alkaline phosphatase, some of which is carried by vesicles. This cleaves the inhibitory pyrophosphate and simultaneously generates free phosphate ions for mineralization, acting as the foci for calcium and phosphate deposition. Vesicles may initiate some of the early mineralization events by rupturing and acting as a centre for crystals to grow on. Bone mineral may be formed from globular and plate structures, and via initially amorphous phases.[34][35]

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