Bone or Osseous Tissue

The skeleton is an endoskeleton. It is a living structure, very metabolically active. It is capable of growth, adaptation to bearing weight and repair. It has within it living cells, a blood supply and a nerve supply. The endoskeleton grows at the same time as the rest of the body grows. The skeleton is made up of osseous tissue (bone), bone marrow (blood cell forming tissue), cartilage, dense connective tissue (ligaments and tendons) and adipose tissue.

I. Functions of Bone

A. Static Functions 1. Support The bones of the skeleton act as a structural framework of the body and because it is rigid it can bear weight. It supports soft tissue and provides points of attachment for muscle via the tendons.

2. Movement Some bones meet in moveable joints. The skeletal muscles attach to the skeleton by the tendons. On contracting the skeletal muscles, the tendons pull on the bones to effect movement. The skeleton plays a role in the kind and extent of body movement.

3. Protection The skeleton protects the internal organs of the body. a. Skull and Vertebral Column – protect the brain and spinal cord. b. Thoracic (Rib) Cage - protects the thoracic organs - lungs, heart, blood vessels and thymus gland. c. Pelvis - protects the lower digestive system organs, urinary bladder and reproductive organs.

B. Dynamic Functions 1. Mineral Reservoir Ca, P, Na, K and other minerals are stored in the bones, which contribute to the strength of the bones and the release these minerals maintain homeostatic levels of these ions in the body. 2. Hemopoiesis The red bone marrow of certain bones is the site of blood cell formation. The marrow is housed in the interior spaces of the bone. 3. Storage of Energy The yellow marrow stores energy as fat.

II. Structure of Bone

Using long bone as an example. The long bones are longer than they are wide and are slightly curved. These bones have a long axis. The shaft of the bone is the diaphysis, the ends of the long bone is the epiphysis. The long bones have a relatively thick amount of compact bone to the outside and cancellous (spongy) bone to the inside.

1 A. Gross Anatomy

1. Shaft or Diaphysis The diaphysis is mainly compact bone. In the center of the diaphysis is a hollow cavity, the medullary or marrow cavity. In the adult, the cavity is filled with fat (yellow marrow cavity). In young individuals especially newborns, the marrow is red bone marrow (hemopoietic tissue). The medullary cavity is lined by a thin layer of connective tissue, the endosteum. It is from the endosteum that the bone can grow in thickness from the inside by appositional growth. The cancellous or spongy bone is covered by the endosteum.

2. Ends of the Long Bone or Epiphysis – At the proximal and distal ends of the long bone The epiphysis has a thin layer of compact bone on the outer surface of the ends of the long bone. The central region of the epiphysis is filled with interconnecting plate or trabeculae of cancellous bone. The spaces between the trabeculae of the cancellous bone contain red bone marrow.

3. Metaphysis – It is the region where diaphysis and epiphysis join. In children, the diaphysis and epiphysis are separated by an epiphyseal hyaline cartilage plate that provides for the bone to increase in length by interstitial growth. The cartilage plates are in the metaphysis of the long bone. In the adult, the epiphyseal cartilage plates of the metaphysis at either ends of the long bone are replaced by bone, fusing the epiphysis to the diaphysis. This bony junction is called the epiphyseal line.

Blood flow to the bone is by nutrient arteries that enter the bone by holes in the bone, called nutrient foramen. Accompanying the nutrient arteries are nutrient veins and nerves.

The outer surfaces of the diaphysis are covered with a relative thick layer of connective tissue, the periosteum. It is from the inner layer of the periosteum that the bone grows in thickness from the outside by appositional growth. The periosteum is firmly attached to the bone by collagenous bundles (Sharpey’s fibers) that penetrate the bone. The ligaments and tendons attach to the bone by the periosteum.

There is no periosteum over the epiphysis, the epiphyseal bone is covered with articular cartilage. The articular cartilage allows for movement at freely moveable joints by reducing friction and also acting as a shock absorber when the bones move.

B. Microscopic Anatomy of Bone or Osseous Tissue

1. Compact Bone or Osteon The basic unit of compact bone is the osteon (Haversian system). Each osteon in cross section consist of concentric lamellae (layers) of bone surrounding a central (Haversian) canal. Between the lamellae are lacunae that contain mature bone cells, the osteocytes. Radiating from the lacunae are tiny canals, the canaliculi. The osteocyte processes reside in the canaliculi in living bone.

In the center of the osteon is a central canal. Each central canal contains a blood capillary. The blood capillary in the central canal is a branch from a larger vessel. This larger vessel lies in a canal at right angles to the central canal, the perforating (Volkmann's) canal. Nutrient blood vessels that penetrates the surface of the bone through nutrient foramen reside in the perforating canals.

Areas between the osteons contain intersitial lamellae, which are fragments of osteons that are being replaced as bone is remodeled or growing. 2 On the surface of the bone, beneath the periosteum, there are several outer circumferential lamellae which follow the circumference of the shaft. The inner circumferential lamellae encircle the marrow cavity are beneath the endosteum.

2. Spongy Bone or Cancellous Bone

The basic unit of structure of the cancellous bone is the trabecula. The lamellae are arranged as a thin plate of bone to form the trabecula. The osteocytes are embedded in lacunae with the osteocyte processes in the canaliculi.

C. Comparison between Compact and Spongy Bone 1. Spongy or Cancellous Bone Spongy bone has many spaces filled with red marrow for blood cell production. Spongy bone is made up of thin plates of bone, the trabeculae. The trabeculae consist of lamellae. At the edge of the lamellae there are lacunae with osteocytes and canaliculi with ostocyte processes. The surfaces of the trabeculae are covered with endosteum. In the endosteum there are osteoblasts and osteoclasts.

Spongy bone is found in short bones, flat bones, irregular shaped bones and the epiphysis of long bones. The function of spongy bone is support, and helps resist stress with a minimum of added weight. It is also as an area for blood cell production. The name for the marrow space found in the spongy bone is the diploe.

2. Compact Bone or Osteon Compact bone contains few spaces. It is composed of concentric lamellae, the Haversian system or osteon. Compact bone is deposited over spongy bone. It is thicker in the diaphysis than in the epiphysis. The function of compact bone is to provide protection, support, resist stress of weight placed on the bone. The surfaces of compact bone are covered with periosteum.

3. Function of Compact Bone and Spongy Bone with Regard to Weight Bearing – see p. 4.

D. Composition - Chemical Nature of Bone Intercellular Substance (Ground Substance and Fibers)

The ground substance is composed of organic chemicals and inorganic salts. 1. Organic Chemicals - the organic chemicals form a homogenous ground substance, the osteoid. The osteoid is chemically a mixture of hyaluronic acid and chrondroitin sulfate. The collagenous fibers are irregularly arranged in the osteoid.

2. Inorganic Salts - the inorganic salts of Ca and PO4 are embedded in the osteoid and around the fibers. The salts are formed into crystals called hydroxyapatite crystals. The inorganic salts constitute 50%, organic matter 25% and water 25% of the weight of bone. The process of calcification of the osteoid occurs only in the presence of the collagenous fibers. The mineral salts crystallize first in the osteoid and then around the fibers.

3. Collagenous Fibers - the collagenous fibers give the bone great tensile strength, i.e., resist stretching and twisting and flexibility. The salts allow bone to resist compression by making the bone hard. The combination of collagenous fibers and crystallized salts makes bone flexible and strong (hard) without being brittle. The same principle is used in reinforced concrete, the steel rods gives tensile strength, the cement gives compressional strength. These two properties of the bone can be seen by: (1) Baking bone destroys the osteoid and collagenous fibers. The bone is brittle as only the mineral salts 3 remain. (2) Placing bone in acetic acid (vinegar) dissolves the mineral salts (the inorganic material), the bone becomes rubbery and flexible as the collagenous fibers and osteoid remain.

III. Factors that Affect Bone Development and Maintenance

A. Mechanical Stress and Exercise Bone is a living tissue, it is constantly being remodeled as its strength is adjusted in proportion to stress to which it is subjected. In response to stress there is increased amounts of collagenous fibers and inorganic salts deposited in the bone, the bone thickens. In those areas of bone not subjected to stress, salts are withdrawn from the bone and the bone thins. Bone is subjected to two major stresses: 1. Mechanical Stress or Gravitational Forces Mechanical stress results from supporting weight of the body. In weightless conditions of space travel, bones do not grow and degenerate. 2. Exercise or Functional forces Exercise result from pull exerted on the bones by contracting muscles. When functional forces decrease, such when a bone is in a cast bone does not grow and degenerates. Gravitational and functional forces alter the form of the skeleton. Gravitational forces - as a person increases or decreases weight, skeleton must become heavier or lighter to support the weight. Functional forces - as muscles become stronger due to exercise, bone must become stronger, otherwise the muscle will break the bone to which it is attached. How does stress on the bone cause bone to thicken and thin? The pressure or stress on the bone affects the pH of the extracellular fluids of bone and the electric fields in the bone causing bone growth, thickening and remodeling. Alkaline pH activates the enzyme, alkaline phosphatase in the osteoblasts to increase bone formation and thickens the bone. In other parts of the bone not subjected to pressure, the pH of the extracellular fluids activates acid phosphatase in the osteoclasts causing bone resorption and decreasing bone formation. When the bone is stressed, the stress causes the mineralized crystals to generate minute electric fields which attract osteoblasts to the area of the stress. The electric fields prevents the PTH from stimulating the osteoclasts, thus allowing bone deposition.

B. Hormones and Bone’s Role in Ca++ Homeostasis Bone as a Ca++ reservoir. Many endocrine hormones influence bone development and regulate blood Ca++ levels. Ca++ levels in the body must be maintained for muscle and nerve function and blood clotting. The homeostatic blood Ca++ level is 8.5-11mg/100mL. The blood Ca++ is regulated by control of Ca++ resorption from the bone into the blood or Ca++ deposition from the blood into the bone depending on the blood Ca++ levels. Hormones that regulate the homeostatic Ca++ levels of the body. 1. Parathormone (PTH) from the parathyroid gland PTH increases number and activity of osteoclasts in the bone, to increase resorption of bone. The increased resorption releases Ca++ from the bone into the blood to increase Ca++ in the blood ++ (hypercalcemia). Under the influence of the PTH the kidney decreases Ca excretion but increases PO4 excretion. PTH increase vitamin D production. Low blood Ca++ stimulates PTH synthesis, high blood Ca++ inhibits PTH release from the parathyroid by negative feedback. 2. Calcitonin from the thyroid gland Calcitonin opposes PTH by decrease resorption of bone by decreasing the activity of the osteoclasts. This lowers the blood Ca level (hypocalcemia). Calcitonin increases osteoblast activity to increase 4 Ca++ in the bone matrix, increase bone formation and increase Ca++ loss by the kidney. Remodeling of bone involves interaction of these two hormones. 3. Growth Hormone (GH) from the pituitary gland GH stimulates protein synthesis, growth of skeleton and growth in general. GH enhances Ca++ ions and amino acid absorption by osteoblasts and incorporation of the amino acids into collagen. 4. Testosterone and Estrogen from the gonads These hormones promote protein synthesis, Ca++ retention, and Ca++ deposition in bone, i.e. fosters bone deposition. However, estrogen causes closure of the epiphyseal plate earlier than testosterone. 5. Insulin, Thyroid Hormones and Adrenal Cortex Hormones These hormones are needed for general body growth, bone growth and maturity.

C. Nutrition Growth and maintenance of bone depend on adequate dietary intake of minerals, vitamins and sufficient levels of the above hormones. A balanced diet must provide for the following essential substances. Anytime there is malnutrition or severe illness during bone growth, the person will be shorter than they were genetically determined to be. 1. Minerals – Ca, PO4, F, Mg, Fe, and Mn 2. Vitamin D (Calcitrol) – synthesized in the kidneys - necessary for absorption of Ca++ from the digestive tract. Vitamin D synthesis is stimulated by PTH and inhibited by high Ca++ in the blood. 3. Vitamin C – necessary in the formation of the protein, collagen. If vitamin C is decreased, defective bone formation occurs, as a low vitamin C prevents normal collagen formation. 4. Vitamin A – necessary for synthesis of chondroitin sulfate, which gives the bone’s ground substance its solid gel-like consistency. 5. Vitamin B12 – it effects osteoblasts activities by acting as a coenzyme for oxidative enzymes in the electron transport chain. 6. Vitamin K – necessary for protein synthesis.

IV. Bone Formation – Osteogenesis or Ossification

A. Pre-natal Bone Development There are two methods of bone formation in the embryo beginning at 6 weeks in utero. 1. Intramembranous Ossification – The bone forms directly from mesenchymal cells which are arranged in sheet-like layers that resemble membranes. Irregular, flat and short bones of the skeleton develop in this manner.

2. Endochondral Ossification – The bone forms from hyaline cartilage which first developed from the mesenchyme. The bones are modeled as cartilage models which are then replaced by bone. The long bones of the skeleton develop in this manner. B. Post-natal Bone Growth 1. Interstitial Growth Growth in length of the long bone is by interstitial growth of the epiphyseal hyaline cartilage plate in the metaphysis. The long bones grow in length from this cartilage plate. This type of bone growth occurs from infancy to early adulthood.

2. Appositional Growth Growth in thickness of the bones of the skeleton is by appositional growth. The bone grows on the outside from the inner layer of the periosteum and from the inside from the endosteum. This growth is capable of occurring throughout life. In the adult this type of bone growth serves mainly for remodeling and repair of bones by bone deposition and bone resorption. 5 Negative Feedback System for Regulation of Blood Ca++ Concentration

Some stimulus (stress) disrupts homeostasis by causing a decrease in

Controlled condition Blood calcium (Ca++) level

Receptors Parathyroid gland cells detect lowered Ca++ concentration Increased production Input of cyclic AMP

Control center PTH gene “turned on” Return to homeostasis Increased release of when response brings Output PTH blood Ca++ level back to normal Effectors Osteoclasts increase Kidneys retain Ca++ bone resorption in blood, excrete PO4 in urine and produce calcitiol

Response Increase in blood Ca++ level

6 Decrease in PTH or Calcitriol (Vit. D) Extracellular Fluid Calcitonin Rate of intestinal absorption Kidneys allow Ca++ decreases for Ca++ Normal Ca++ concentration loss (8.5-11 mg/100 mL)

PTH and Calcitriol PTH and Calcitriol Rate of intestinal absorption Kidneys retain Ca++ ++ increases for Ca and excrete PO4

PTH Calcitonin Factors that increase Osteoclasts release Inhibits osteoclasts blood Ca++ concentrations stored Ca++ by Ca++ in bone matrix promoting bone resorption increased by promoting Factors that decrease osteoblast activity blood Ca++ concentrations

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