Bones and Bone Tissue Notes

Bones and Bone Tissue

The Skeletal System

• Includes bones, joints, and other supporting tissues.
• Bones: Main organs of the system.
  • Adults typically have 206 bones.
  • Each bone includes:
    • Bone (Osseous) Tissue
    • Dense regular collagenous tissue
    • Dense irregular connective tissue
    • Bone Marrow

Functions of the Skeletal System

• Protection: Bones like the skull, sternum, and ribs protect underlying organs.
• Mineral Storage and Acid-Base Homeostasis: Bone stores minerals like calcium, phosphorus, and magnesium salts.
  • These minerals are electrolytes, acids, and bases in the blood, critical for electrolyte and acid-base maintenance.
• Blood Cell Formation: Red Bone Marrow in bones is the site of Hematopoiesis (formation of blood cells).
• Fat Storage: Yellow Bone Marrow in bones contains adipocytes with stored triglycerides.
• Movement: Bones are attachment sites for most skeletal muscles.
  • Muscle contraction pulls on bones, generating movement around a joint.
• Support: The skeleton supports the body's weight and provides structural framework.

Classification of Bone by Shape

• Long Bones: Longer than wide.
  • Examples: bones of the limbs (some are very small).
• Short Bones: About as long as wide (roughly cube-shaped).
  • Examples: wrist and ankle bones.
• Flat Bones: Thin and broad.
  • Examples: most skull bones and bones of the pelvis.
• Irregular Bones: Irregular shapes.
  • Examples: vertebrae.
• Sesamoid Bones: Small, flat, oval-shaped bones located within tendons.
  • Example: kneecap.

Structure of a Long Bone

• Periosteum: Outer dense irregular connective tissue membrane with blood vessels and nerves.
• Perforating Fibers: Collagen anchors that penetrate into bone matrix to attach the periosteum.
• Diaphysis: Shaft of the bone with a Medullary (Marrow) Cavity lined by the Endosteum and filled with marrow.
• Epiphyses: Ends of a long bone (filled with Red Marrow) covered with Articular Cartilage (hyaline cartilage).
• Compact Bone: Hard, dense outer bone that resists linear compression and twisting forces.
• Spongy (Cancellous) Bone: Inner, honeycomb-like bone framework that resists forces in many directions and provides a place for bone marrow.
• Epiphyseal Lines: Remnants of an Epiphyseal (Growth) Plate, which is a line of hyaline cartilage actively growing in children and adolescents.

Structure of Short, Flat, Irregular, and Sesamoid Bones

• Share similarities with long bones but have fewer structures.
• In flat bones, the spongy bone is called Diploë.
• Some flat and irregular bones of the skull have air-filled spaces called sinuses to make the bones lighter.

Blood and Nerve Supply to Bone

• Bones are well supplied with blood vessels and many sensory fibers.
• Blood supply to short, flat, irregular, and sesamoid bones is mainly from vessels in the periosteum that penetrate the bone.
• Blood supply to long bones is from the periosteum and 1 or 2 Nutrient Arteries that enter through a small hole in the diaphysis called the Nutrient Foramen to supply the internal structures.

Red and Yellow Marrow

• Yellow Bone Marrow: Consists mostly of blood vessels and adipocytes.
• Red Bone Marrow: Network of reticular fibers supporting islands of hematopoietic cells.
  • Infants and young children have mostly red bone marrow due to rapid growth, changing to yellow marrow around age 5.
  • Adults have mostly yellow marrow, with red marrow in the pelvic bones, proximal thigh and arm bones, vertebrae, ribs, sternum, clavicles, and shoulder blades.

The Extracellular Matrix of Bone (Bone Matrix)

• Inorganic Matrix: About 65% of bone's total weight.
  • Consists mostly of calcium and phosphorus salts as part of a large mineral called Hydroxyapatite Crystals, which gives bone its strength and resistance to compression.
  • Formula for Hydroxyapatite: $\text{Ca}<em>{10}(\text{PO}</em>4)<em>6(\text{OH})</em>2$ or $\text{Ca}<em>{10}(\text{PO}</em>4)<em>6(\text{CO}</em>3)$
  • Bicarbonate, potassium, magnesium, and sodium salts are also in the inorganic matrix.
• Organic Matrix (Osteoid): About 35% of bone's total weight.
  • Consists of protein fibers (mostly collagen), proteoglycans, glycosaminoglycans, glycoproteins, and bone-specific proteins such as Osteocalcin.
  • Collagen helps bone resist torsion (twisting) and tensile (pulling or stretching) forces and aligns with hydroxyapatite crystals to enhance bone hardness.
  • Osteocalcin binds to calcium ions and hydroxyapatite crystals to organize bone’s inorganic matrix.
  • Glycosaminoglycans and proteoglycans draw water out of the blood vessels and cells to help the ECM resist compression.
  • Glycoproteins bind to both hydroxyapatite crystals and bone cells to bind them together.

Bone Cells

• Bone is dynamic tissue because new bone is continually formed as older bone is broken down.
• Osteoblasts: Build bone and mature into osteocytes.
• Osteocytes: Maintain bone.
• Osteoclasts: Break down bone.

Osteoblasts

• Derived from Osteogenic Cells.
• Cuboidal to columnar cells in the inner periosteum and endosteum.
• Perform Bone Deposition by secreting organic matrix and assisting in the formation of the inorganic matrix.

Osteocytes

• Mature osteoblasts.
• Osteoblasts surround themselves with matrix and become trapped in a cavity called a Lacuna.
• They secrete chemicals to maintain the ECM and recruit osteoblasts to build areas of bone under tension.

Osteoclasts

• Large, multinucleated cells with Ruffled Borders, derived from fusion of cells formed in the bone marrow.
• Reside in internal or external surfaces of bone.
• Responsible for Bone Resorption (breaking down bone ECM).
  • Secrete hydrogen ions ($H^+$) that dissolve the inorganic matrix.
  • Secrete enzymes that break down the organic matrix.
  • Minerals, amino acids, and sugars released from bone enter the osteoclast for delivery to the blood.

Histology of Bone

• Compact Bone: Hard, dense outer shell that resists a great amount of stress.
  • Units are called Osteons or Haversian Systems.
• Spongy Bone: Resists forces from many directions and forms a protective framework for the bone marrow, although not weight-bearing.
  • Organized into branching "ribs" of bone called Trabeculae.

Compact Bone: Osteon Structure

• Lamellae (Concentric Lamellae): Rings of very thin layers of bone.
  • Osteons contain 4 to 20 lamellae.
  • Collagen fibers of adjacent lamellae run in opposite directions, which resists twisting and bending forces.
• Central (Haversian) Canal: Contains blood vessels and nerves; lined by endosteum.
• Lacunae: Small cavities between lamellae filled with ECF.
  • About 20,000–30,000 osteocytes and lacunae are found in each cubic millimeter of bone.
• Canaliculi: Tiny canals that connect lacunae.
  • Filled with thin cytoplasmic extensions of osteocytes that contact each other through gap junctions.
• Compact bone is composed of multiple osteons connected by Interstitial Lamellae internally and Circumferential Lamellae in the inner and outer rings that strengthen bone.
• Perforating (Volkmann) Canals: Connect central canals of neighboring osteons and carry blood vessels from the periosteum to the central canals.

Spongy Bone

• Trabeculae: Covered with endosteum; contain concentric lamellae with lacunae and canaliculi housing osteocytes, but no central or perforating canals.
  • Access blood supply from blood vessels in bone marrow.

Bone Formation: Ossification (Osteogenesis)

• Process of bone formation; continues through childhood, with most bones completing the process by age 7.
• Occurs in steps:
  • Primary (Woven) Bone: Immature bone consisting of irregularly arranged collagen bundles, abundant osteocytes, and little inorganic matrix.
    • In most locations, primary bone is resorbed by osteoclasts and replaced by secondary bone.
  • Secondary (Lamellar) Bone: Strong, mature bone with fully formed lamellae and organized, parallel collagen bundles and a higher percentage of inorganic matrix.
• Two forms of ossification:
  • Intramembranous Ossification: Bones are built on a model made of embryonic connective tissue called a mesenchymal membrane; inner spongy bone forms first.
    • Includes many flat bones, including most of the skull, and the clavicles.
  • Endochondral Ossification: Bones are built on a model of hyaline cartilage; outer compact bone forms first.
    • Includes all bones in the body below the head, except the clavicles.

Steps of Intramembranous Ossification

• (1) Osteoblasts develop in the Primary Ossification Center from mesenchymal cells.
  • Mesenchymal cells differentiate into osteogenic cells and then into osteoblasts.
• (2) Osteoblasts secrete organic matrix, which calcifies, and trapped osteoblasts become osteocytes.
  • Calcification is the process in which calcium salts and other components of the inorganic matrix are deposited in the primary ossification center.
• (3) Osteoblasts lay down trabeculae of early spongy bone, and some of the surrounding mesenchyme differentiates into the periosteum.
  • Some of the vascular tissue will become bone marrow.
• (4) Osteoblasts in the periosteum lay down early compact bone.
  • The matrix is remodeled to form immature compact bone.
  • Larger bones require fusion of primary ossification centers.
  • Fontanels or “soft spots” in newborn skulls represent areas of incomplete fusion.

Endochondral Ossification

• Begins during the fetal period for most bones, but some, such as those in the wrist and ankle, ossify later.
• The hyaline cartilage model consists of Chondrocytes and cartilage ECM surrounded by a Perichondrium and immature cartilage cells called Chondroblasts.
• Begins at primary ossification centers, but long bones also contain Secondary Ossification Centers within their epiphyses.

Steps of Endochondral Ossification

• (1) The chondroblasts in the perichondrium differentiate into osteoblasts.
  • Chemical signals trigger the change from chondroblasts to osteogenic cells to osteoblasts.
• (2) The bone begins to ossify from the outside:
  • 2a. Osteoblasts build the Bone Collar on the bone’s external surface.
  • 2b. Simultaneously, the internal cartilage begins to calcify, and the chondrocytes die.
• (3) In the primary ossification center, osteoblasts replace the calcified cartilage with early spongy bone; The secondary ossification centers and medullary cavity develop.
  • Epiphyses also begin to ossify.
• (4) As the medullary cavity enlarges, the remaining cartilage is replaced by bone; The epiphyses finish ossifying.
  • Cartilage remains in the epiphyseal plates until growth in bone length ceases and as the articular cartilage for life.

Differences Between Intramembranous and Endochondral Ossification

• (1) The types of bones that form by each type
  • Flat bones form by intramembranous ossification within a fibrous membrane because flat bones and membranes are both flat.
  • Long and short bones form by endochondral ossification because long bones have enlarged ends and short bones are cube-shaped, which could not form from membranes
• (2) The order in which compact and spongy bone form
  • In endochondral ossification, the hyaline cartilage has a perichondrium, which becomes a periosteum that produces osteoblasts; They secrete compact bone first, followed by spongy bone forming inside.
  • In intramembranous ossification, the fibrous membrane model has no perichondrium to become a periosteum, so there are no outer osteoblasts to make the initial compact bone; Instead, the osteoblasts come from cells inside the membrane in ossification centers and make spongy bone first. Only at the end of the process does a periosteum form

Osteoporosis and Healthy Bone Tissue

• Osteoporosis: Bone disease caused by inadequate inorganic matrix in the ECM.
  • Makes bone brittle and increases the risk of fractures, which also heal more slowly.
• Causes: Dietary factors (calcium and vitamin D deficiency), female sex, advanced age, lack of exercise, hormonal factors (lack of estrogen in postmenopausal women), genetic factors, diseases of the skin, digestive and urinary systems.
• Preventative Measures and Treatments: Ensure adequate intake of calcium and vitamin D, engage in weight-bearing exercises, replace estrogen (if appropriate), use drugs that inhibit osteoclasts or stimulate osteoblasts.

Bone Growth in Length: Longitudinal Growth

• Lengthening of long bones when chondrocytes divide at the Epiphyseal Plate.
• The Epiphyseal Plate has 5 Different Zones of Cells:
  • (1) Zone of Reserve Cartilage: Cells are not directly involved in bone growth but can divide if needed.
  • (2) Zone of Proliferation: Chondrocytes are actively dividing in lacunae; most mitotic activity.
  • (3) Zone of Hypertrophy and Maturation: Contains mature chondrocytes.
  • (4) Zone of Calcification: Contains dead chondrocytes, some of which are calcified; far from blood supply.
  • (5) Zone of Ossification: Contains calcified chondrocytes and osteoblasts to build bone.
  • Zones 2–5 are actively involved in longitudinal growth, and as cells divide, the cells "above" them progressively become part of the next zones.

Steps of Longitudinal Growth

• (1) Chondrocytes divide in the zone of proliferation.

• (2) Chondrocytes that reach the next zone enlarge and mature.

  • Lacunae surrounding the chondrocytes are larger here.

• (3) Chondrocytes die, and their matrix calcifies.

• (4) Calcified cartilage is replaced with bone.

  • In the zone of ossification, osteoblasts invade the calcified cartilage and lay down bone; Osteoclasts resorb the calcified cartilage/bone, which is replaced by bone.

• Longitudinal growth stops when rate of mitosis slows, ossification continues, and Epiphyseal plate shrinks, overtaken by zones of calcification and ossification.

• When proliferation zone completely ossifies (between 13 and 21 years), plate is "closed", leaving Epiphyseal Line remnant.

Bone Growth in Width: Appositional Growth

• Growth of all bones in width; may continue after bone growth in length ceases.
• Osteoblasts between the periosteum and the bone surface lay down new bone.
• Begins with the formation of new circumferential lamellae; as new lamellae are added, the deeper circumferential lamellae are removed or incorporated into osteons.
• Primarily thickens the compact bone of the diaphysis; osteoclasts in the medullary cavity digest the inner circumferential lamellae, so as bones increase in width, their medullary cavities enlarge as well.

The Role of Hormones in Bone Growth

• Growth Hormones: Group of chemicals secreted by endocrine glands into the blood; some have direct effects on bone growth.
• (1) Growth Hormone: Produced by the anterior pituitary gland; secreted throughout life but in the highest amounts during infancy and childhood.
  • Functions in bone include:
    • Increase mitosis of chondrocytes in the epiphyseal plate, promoting longitudinal growth.
    • Increase activity of osteogenic cells, including their activity in the zone of ossification.
    • Directly stimulate osteoblasts in the periosteum, triggering appositional growth.
• (2) Testosterone: Male sex hormone.
  • Increases appositional growth, causing bones in males to be much thicker with greater calcium deposits than in females.
  • Increases mitosis at the epiphyseal plate, so “growth spurts” during puberty accompany large increases in testosterone.
  • Accelerates closure of the epiphyseal plates, so most boy’s epiphyseal plates are closed by age 16–17.
• (3) Estrogen: Female sex hormone.
  • Similar effects as testosterone, although less pronounced.
  • Epiphyseal plates generally close by age 14–15.

Bone Remodeling

• The continual process of bone formation (by Bone Deposition) and bone loss (by Bone Resorption).
• Occurs for many reasons:
  • Maintenance of calcium ion homeostasis
  • Bone repair
  • Replacement of primary bone with secondary bone
  • Replacement of older, brittle bone with newer bone
  • Bone adaptation to tension and stresses
• In healthy adult bone, bone formation and bone loss occur simultaneously by osteoblasts and osteoclasts, respectively.
• In children, bone formation outweighs bone loss.

Bone Deposition

• Osteoblasts in the periosteum and endosteum make the components of the organic matrix and facilitate the formation of the inorganic matrix.
  • They secrete proteoglycans and glycoproteins that bind to calcium ions, and they secrete the vesicles containing the calcium ions, ATP, and enzymes.
  • The vesicles bind to collagen fibers, the calcium ions crystallize, causing the vesicle to rupture, which begins the process of calcification.

Bone Resorption

• Osteoclasts secrete hydrogen ions ($H^+$) and enzymes from their ruffled borders onto the bone ECM.
  • Hydrogen ions make the pH more acidic, which breaks down the hydroxyapatite crystals in the inorganic matrix.
    • Calcium and other minerals may be used by the body for other needs.
  • Enzymes catalyze reactions that break down proteoglycans, glycosaminoglycans, and glycoproteins, which are taken into the osteoclasts for reuse.

Bone Remodeling in Response to Tension and Stress

• The heavier the load a bone carries, the more bone tissue is deposited in that bone.
  • Compression: Act of pressing together; occurs when bones are pressed between body’s weight and the ground; stimulates bone deposition.
  • Tension: Stretching force; stimulates bone deposition.
  • Pressure: Application of a continuous downward force; stimulates bone resorption.

Other Factors Influencing Bone Remodeling

• Hormones:
  • Testosterone strongly promotes bone deposition, while estrogen depresses osteoclast activity.
• Age:
  • Hormone levels decline with advancing age, such as growth hormone, which causes a reduction in protein synthesis, and estrogen, which reduces the protective effects of the hormone on bone remodeling.
• Nutrient Intake:
  • Calcium Ion Intake: Required for bone deposition.
  • Vitamin D Intake: Promotes calcium ion absorption in the intestines and prevents calcium loss in the urine; inadequate amounts in children cause Rickets, which results in bone deformities, fractures, and muscle weakness.
  • Vitamin K Intake: Required for osteocalcin to bind to calcium ions; promotes proliferation of osteoblasts, increases their lifespan, and causes them to deposit more matrix; inhibits osteoclast division and activity.
  • Vitamin C Intake: Vitamin C is required for synthesis of collagen.
  • Protein Intake: Adequate protein intake is needed for osteoblasts to synthesize collagen fibers needed for the organic matrix of bone.
    • However, if protein intake is too high, this may decrease the pH of the blood, which causes calcium and phosphate ions to be resorbed from the bone to buffer the pH changes.

Bone Remodeling and Calcium Ion Homeostasis

• Calcium ions are required for many critical processes, including contraction of the heart and skeletal muscles, transmission of nerve impulses, and blood clotting.
• Calcium ion concentration in the blood is maintained using negative feedback loops controlled by hormones.
  • Parathyroid Hormone (PTH): Stimulates effects that increase blood calcium levels; produced in the parathyroid glands.
  • Calcitonin: Stimulates effects that decrease blood calcium levels; produced in the thyroid gland; not as potent in adults.

Negative Feedback Loop to Increase Blood Calcium

• (1) Stimulus: Blood calcium ion level decreases below the normal range.
• (2) Receptor: Parathyroid gland cells detect a low blood calcium ion level.
• (3) Control Center: Parathyroid gland cells increase their release of PTH into the blood.
• (4) Effector/Response: PTH stimulates effects that increase the blood calcium ion level.
• (5) Return to Normal Range: Parathyroid gland cells detect the return of the calcium ion level to the normal range, and the cells decrease the release of PTH.

Bone Repair: Steps of Fracture Healing

• (1) A hematoma fills the gap between the bone fragments
  • Hematoma: Ruptured blood vessels bleed into the injured site, cutting off blood supply to damaged area and bone cells die
• (2) Fibroblasts and chrondroblasts infiltrate the hematoma, and a soft callus forms
  • Fibroblasts form dense irregular connective tissue and chondroblasts secrete hyaline cartilage; these 2 components produce the soft callus
• (3) Osteoblasts build a bone callus
  • Over several weeks, osteoblasts from the periosteum lay down a collar of primary bone called bone callus
• (4) The bone callus is remodeled and primary bone is replaced with secondary bone
  • Over several months, primary bone is resorbed and replaced with secondary bone; The bone callus often remains visible following full healing

Classes of Fractures

• Simple (Closed) Fractures: Skin and surrounding tissue remain intact.
• Compound (Open) Fractures: Damage around the fracture

Treatment of Fractures

• Stabilization of the fracture, followed by immobilization for about 6 weeks.
• Closed Reduction: Bone ends are brought into contact.
• Open Reduction: Fracture is surgically fixated with plates, wires, and/or screws.

Types of Fractures

• Spiral: Resulting from twisting forces applied to the bone.
• Compression: Fracture in which the bone is crushed under the weight it is meant to support; common in the elderly and those with reduced bone mass.
• Comminuted: Fracture in which the bone is shattered into multiple fragments; difficult to repair.
• Avulsion: Fracture in which a tendon or ligament pulls off a fragment of bone; often seen in ankle fractures.
• Greenstick :Fracture in which the bone breaks on one side but only bends on the other side, similar to the break observed when a young (“green”) twig is bent; common in children, whose bones are more flexible.
• Epiphyseal: Fracture that involves at least part of the epiphyseal plate; occurs only in children and young adults; may interfere with growth.