Bone Development, Classification, and Anatomy

Skeletal Cartilage: Structure and Nutrition

• Skeletal cartilage, such as the type seen, lacks both blood vessels and nerves.
• Chondrocytes (cartilage cells, derived from $\text{chondro} = \text{cartilage}$ and $\text{cyte} = \text{cell}$) obtain their nourishment exclusively through diffusion.
• Perichondrium (from $\text{peri} = \text{surrounding}$) is a membrane that encapsulates the cartilage and contains blood vessels.
• Nutrients from the blood vessels within the perichondrium diffuse into the avascular cartilage to supply the chondrocytes.
• In the embryonic stage, the human skeleton initially develops as hyaline cartilage, a specific type of cartilage, before undergoing calcification and transforming into bone.

Types of Cartilage and Their Locations

Three primary types of cartilage exist, as previously covered in the tissues chapter:

1. Hyaline Cartilage:
   • Composed of collagen fibers.
   • It is the most abundant type of cartilage in the body.
   • Locations: Costal cartilage (rib cartilage), articular cartilage (at the ends of long bones), nasal cartilage, and within the respiratory tract.
2. Fibrocartilage:
   • Also contains collagen fibers.
   • Possesses very high tensile strength.
   • Locations: Pubic symphysis, menisci of the knee, and intervertebral discs.
3. Elastic Cartilage:
   • Characterized by a higher proportion of elastic fibers.
   • Allows for significant stretching and recoiling abilities.
   • Locations: External ear cartilage and the epiglottis (note the 'e' starting each location, similar to 'elastic').

Cartilage Growth

There are two main mechanisms of cartilage growth:

1. Appositional Growth (Growth from the outside):
   • Cells in the perichondrium (specifically chondroblasts) secrete new cartilage matrix against the external face of existing cartilage.
   • This process adds new cartilage to the surface, thickening the structure from the outside in.
2. Interstitial Growth (Growth from within):
   • Chondrocytes within the cartilage lacunae divide and secrete new matrix.
   • This expands the cartilage from within, increasing its overall size.

Note: Cartilage calcification is the hardening of cartilage due to the deposition of calcium salts. It is not considered bone, but hardens significantly, sharing some properties with bone.

Bone Classification and Functions

The adult human skeleton comprises $\text{206}$ bones, categorized into two main groups:

1. Axial Skeleton:
   • Consists of bones from the skull, vertebral column (spine), and rib cage.
   • (Illustrated in blue in diagrams).
2. Appendicular Skeleton:
   • Includes the bones of the upper and lower extremities (limbs), as well as the shoulder (pectoral) girdle and pelvic girdle.
   • (Illustrated in beige in diagrams).

Bones perform six crucial functions:

1. Support: Provides a rigid framework for the body, supporting soft organs and acting as attachment sites for muscles.
2. Protection: Encapsulates and safeguards vital organs (e.g., skull protects the brain, rib cage protects the heart and lungs).
3. Movement: Bones act as rigid levers, allowing skeletal muscles to move the body and its parts during locomotion (ambulation).
4. Mineral Storage: Serves as a reservoir for vital minerals, primarily calcium and phosphorus, which can be released into the bloodstream as needed.
5. Blood Cell Formation (Hematopoiesis): Red blood cells, white blood cells, and platelets are produced within the red bone marrow, a process known as hematopoiesis.
6. Triglyceride (Fat) Storage: Yellow bone marrow, found in the medullary cavities of long bones, stores triglycerides, serving as an energy reserve.

Bone Shapes

Bones are classified into five main types based on their shape:

1. Long Bones:
   • Defined as being longer than they are wide.
   • Despite their name, some long bones can be quite small (e.g., phalanges, finger bones, are considered long bones because they are longer than they are wide, even if tiny).
   • Characterized by a shaft (diaphysis) and enlarged ends (epiphyses).
   • Examples: All bones of the limbs, except for the patella (kneecap), carpals (wrist bones), and tarsals (ankle bones).
2. Short Bones:
   • Approximately cube-shaped, meaning they are roughly equal in length, width, and thickness.
   • Examples: Carpals (wrist bones) and tarsals (ankle bones).
3. Sesamoid Bones:
   • A specialized type of short bone that develops within a tendon.
   • Example: The patella (kneecap).
4. Flat Bones:
   • Thin, flattened, and typically curved.
   • Examples: Most skull bones (cranial bones), the sternum (breastbone), scapulae (shoulder blades), and ribs.
5. Irregular Bones:
   • Bones with complex, intricate shapes that do not fit into any of the other classifications.
   • Examples: Vertebrae, pelvic bones, sacrum, and some facial and skull bones.

Bone Markings

Bones feature surface irregularities known as bone markings. These can be bulges, depressions, or holes, each serving specific functions:

• Bulges/Projections: Serve as attachment sites for ligaments (bone to bone) and tendons (skeletal muscle to bone).
• Depressions: Often form joint surfaces or provide passageways for muscles to rest upon.
• Holes/Openings: Act as channels for blood vessels and nerves.

Key bone marking terms and their definitions:

• Crest: A narrow, prominent ridge of bone (e.g., iliac crest on the ilium).
• Process: Any bone prominence or bulge (general term).
• Spine: A sharp, slender, or pointed projection (a type of process, e.g., spinous process of a vertebra).
• Condyle: A rounded articular (joint) projection (e.g., mandibular condyle where the jaw meets the skull at the Temporomandibular Joint - TMJ).
• Foramen: An opening or hole through a bone, typically for the passage of blood vessels and nerves.
• Meatus: A canal-like or tunnel-like opening (e.g., external acoustic meatus, the ear canal).
• Fossa: A shallow, basin-like depression or indentation in a bone (resembles a bowl).
• Fissure: A narrow, slit-like opening or crack in a bone (e.g., fissures within the eye orbit).

Bone Texture: Compact and Spongy Bone

Bone tissue exhibits two distinct textures:

1. Compact Bone:
   • Dense and solid, forming the outer layer of all bones.
   • It is the visible bone when viewing a skeleton.
2. Spongy Bone (Cancellous Bone):
   • Located in the interior of bones, it has a honeycomb-like appearance due to a network of bony plates called trabeculae.
   • The spaces within spongy bone can be filled with either red bone marrow (hematopoietic tissue) or yellow bone marrow (fatty tissue).

Gross Anatomy of a Long Bone

Long bones, characterized by being longer than wide, have distinct anatomical regions:

• Diaphysis: The elongated, narrow shaft of the long bone. It is primarily composed of compact bone.
  • Medullary Cavity: A hollow space within the diaphysis, in adults, it is typically filled with yellow bone marrow. In growing individuals, it contains red bone marrow.
• Epiphysis: The enlarged, bulged ends of the long bone. Each long bone has two epiphyses (proximal and distal).
  • Spongy Bone: The interior of the epiphyses is primarily composed of spongy bone.
• Epiphyseal Plate (Growth Plate): A disc of hyaline cartilage found in growing bones, located between the diaphysis and epiphysis. It is the site of longitudinal bone growth.
• Epiphyseal Line: In adults, after growth has ceased, the epiphyseal plate ossifies and becomes a thin line of bone, visible as the epiphyseal line.
• Articular Cartilage: A layer of hyaline cartilage covering the joint surfaces of the epiphyses, reducing friction and absorbing shock during joint movement.
• Periosteum: A tough, fibrous membrane that covers the external surface of all bones, except for the joint surfaces. It has two layers:
  1. Fibrous Layer: Outer layer, dense irregular connective tissue.
  2. Osteogenic Layer: Inner layer, contains osteogenic cells (stem cells), osteoblasts (bone-forming cells), and osteoclasts (bone-resorbing cells).
  • Richly supplied with nerve fibers and blood vessels.
  • Securely anchored to the bone by strong collagen fibers called Sharpey's fibers (or perforating fibers).
• Endosteum: A delicate connective tissue membrane that lines the internal surfaces of bone. It covers the trabeculae of spongy bone and lines the medullary cavity.
  • Also contains osteogenic cells, osteoblasts, and osteoclasts.

Anatomy of Short, Irregular, and Flat Bones

Unlike long bones, short, irregular, and flat bones do not possess a diaphysis and epiphysis. However, they do have a periosteum covering their outer surfaces and an endosteum lining their internal cavities.

• They typically contain spongy bone (trabeculae) in their interior, which may house hematopoietic (red) bone marrow.
• Diploë: In flat bones (specifically, cranial bones), the spongy bone is sandwiched between two layers of compact bone, forming a structure called the diploë (e.g., in the parietal bone of the skull).

Red Bone Marrow (Hematopoietic Tissue)

Red bone marrow is the primary site of hematopoiesis (blood cell production).

• In Adults:
  • Primarily found in the spongy bone of the heads (epiphyses) of the femur (thigh bone) and humerus.
  • Also extensively located in the diploë of flat bones (like the skull and sternum) and in some irregular bones (like the hip bone and vertebrae).
• In Infants:
  • Have a much higher demand for blood cell production compared to adults.
  • Red marrow is found more widely, including in all flat bones (diploë), the epiphyses of long bones, and within the medullary cavities of all long bones.
  • Essentially, the entire interior of an infant's long bones is filled with red bone marrow.

Bone Cells

Bone tissue contains four main types of cells, each with a specialized role in bone formation, maintenance, and breakdown:

1. Osteogenic Cells (Osteoprogenitor Cells):
   • These are mitotic stem cells found in the periosteum and endosteum.
   • They can differentiate into osteoblasts when bone formation is required.
2. Osteoblasts:
   • Bone-forming cells. They actively secrete the bone matrix, which is initially an unmineralized gel-like substance called osteoid.
   • Osteoid is composed of ground substance and collagen fibers, providing strength.
   • Osteoblasts continue to secrete osteoid until they become entrapped within their own matrix, at which point they mature into osteocytes.
3. Osteocytes:
   • Mature bone cells that reside in small cavities within the bone matrix called lacunae.
   • They maintain the bone matrix, acting as stress or strain sensors, and communicate with other bone cells to initiate bone remodeling in response to mechanical stimuli.
4. Osteoclasts:
   • Large, multinucleated cells responsible for bone resorption (breaking down bone).
   • They secrete potent enzymes and acids to dissolve the organic and inorganic components of the bone matrix, releasing minerals (like calcium) into the bloodstream.
   • This process is crucial for bone remodeling and calcium homeostasis.

Microscopic Anatomy of Compact Bone (Osteon)

Compact bone is organized into repeating structural units called osteons (also known as the Haversian system).

• Osteon Structure: Each osteon is a cylindrical unit, running parallel to the long axis of the bone.
  • Lamellae: Each osteon consists of multiple concentric rings or layers of bone matrix, called lamellae. Collagen fibers within adjacent lamellae run in opposite directions, enhancing bone's ability to withstand twisting forces (torsional stresses).
  • Central (Haversian) Canal: Running through the center of each osteon, this canal contains blood vessels (arteries and veins) and nerve fibers, supplying the osteon.
  • Lacunae: Small, unoccupied spaces (caves) located between the lamellae, where osteocytes reside.
  • Canaliculi: Tiny, hair-like canals that radiate from the lacunae, connecting them to each other and to the central canal. These allow for nutrient and waste exchange, and communication between osteocytes.
• Perforating (Volkmann's) Canals: Canals that run perpendicular to the central canals, connecting the blood and nerve supply of the periosteum to the central canals and the medullary cavity.
• Circumferential Lamellae: Layers of lamellae that extend around the entire circumference of the diaphysis, just deep to the periosteum and superficial to the endosteum, providing resistance to twisting.
• Interstitial Lamellae: Incomplete lamellae that fill the gaps between intact osteons, often remnants of old, remodeled osteons.

Microscopic Anatomy of Spongy Bone (Trabeculae)

Spongy bone is less organized than compact bone and lacks osteons.

• Trabeculae: The main structural unit of spongy bone. These are thin, needle-like or flat pieces of bone (spicules) that form an irregular lattice or honeycomb-like network.
• The spaces between the trabeculae are filled with red or yellow bone marrow.
• Stress Lines: Although appearing random, trabeculae are precisely arranged along lines of stress, allowing spongy bone to resist stress from multiple directions and lighten the bone.
• Nutrients reach osteocytes in spongy bone via diffusion through the canaliculi from blood vessels in the endosteum surrounding the trabeculae.

Chemical Composition of Bone

Bone matrix is a remarkable composite material, deriving its strength and resilience from both organic and inorganic components:

1. Organic Components (constituting about $\text{35\%}$ of bone mass):
   • Bone Cells: Osteogenic cells, osteoblasts, osteocytes, and osteoclasts.
   • Osteoid: The unmineralized portion of the bone matrix secreted by osteoblasts.
     • It is a gel-like substance, not hard.
     • Composed primarily of ground substance (proteoglycans and glycoproteins) and collagen fibers.
     • Collagen fibers provide tensile strength and flexibility, preventing bone from snapping under tension.
2. Inorganic Components (constituting about $\text{65\%}$ of bone mass):
   • Mineral Salts (Hydroxyapatites): Primarily calcium phosphate crystals ($\text{Ca}_ {10} (\text{PO}<em>4)</em>6 (\text{OH})_2$) .
   • These mineral salts precipitate into the osteoid, crystallizing around the collagen fibers.
   • This mineralization process is responsible for bone's exceptional hardness and resistance to compression, making it a solid structure.

Bone Development (Ossification/Osteogenesis)

Ossification or osteogenesis refers to the process of bone tissue formation.

• Embryonic Stage: Bone formation begins remarkably early, around the $\text{2}^{ \text{nd} }$ month of embryonic development.
  • Recall that the embryonic skeleton is initially composed of hyaline cartilage, which serves as a model for most bones.
• Postnatal Growth: Bone development and growth continue from this early stage until late adolescence or early adulthood, when bone lengthening typically ceases.
• Lifelong Remodeling and Repair: Even after growth stops, bones are dynamic tissues. They constantly undergo remodeling (breakdown and rebuilding) and repair throughout an individual's entire life in response to mechanical stress and injury.

Types of Ossification

There are two distinct mechanisms by which bones form during embryonic development:

1. Intramembranous Ossification:
   • This process forms flat bones of the cranium (skull) and the clavicles (collarbones).
   • Involves the development of bone directly from a fibrous membrane, without a preceding cartilage model.
2. Endochondral Ossification:
   • This is the more common method, forming the vast majority of bones in the skeleton (all bones except the cranial flat bones and clavicles).
   • Bone development occurs by replacing a pre-existing hyaline cartilage model.

Intramembranous Ossification Process

This process forms cranial flat bones and clavicles through four main stages:

1. Ossification Center Appears in the Fibrous Connective Tissue Membrane:
   • Mesenchymal cells (stem cells capable of becoming various connective tissue cells) cluster in the fibrous membrane.
   • In this specific environment, these mesenchymal cells differentiate into osteoblasts.
   • Osteoblasts begin to secrete osteoid (unmineralized bone matrix).
2. Osteoid is Secreted within the Fibrous Membrane and then Calcifies:
   • Osteoblasts continue to secrete osteoid, expanding the bone region.
   • Some osteoblasts become trapped within the osteoid they have secreted, and once encased, they differentiate into osteocytes (mature bone cells) located in lacunae.
   • The secreted osteoid then undergoes calcification, hardening as mineral salts are deposited.
3. Woven Bone and Periosteum Form:
   • As osteoid secretion and calcification continue, a network of embryonic bone, called trabeculae (or woven bone), forms around the invading blood vessels.
   • Blood vessels infiltrate the area, bringing nutrients and further stimulating growth.
   • The remaining mesenchymal cells in the surrounding membrane differentiate to form the periosteum (the outer bone membrane).
4. Lamellar Bone Replaces Woven Bone, Just Deep to the Periosteum. Red Marrow Appears:
   • More mature, compact lamellar bone replaces the initial woven bone at the surfaces.
   • Spongy bone persists internally (the diploë in flat bones).
   • Red bone marrow begins to fill the spaces within the spongy bone trabeculae.

Endochondral Ossification Process

This process forms most bones of the skeleton (excluding flat cranial bones and clavicles) by replacing a hyaline cartilage model. It involves several key steps:

1. Bone Collar Forms Around the Diaphysis of the Hyaline Cartilage Model:
   • In the embryo, a hyaline cartilage model roughly replicates the future bone shape.
   • The perichondrium (membrane surrounding cartilage) contains chondroblasts.
   • These chondroblasts in the perichondrium differentiate into osteoblasts.
   • Osteoblasts secrete bone matrix, forming a bony collar (compact bone) around the diaphysis of the cartilage model.
2. Cartilage in the Center of the Diaphysis Calcifies and then Develops Cavities:
   • Chondrocytes within the center of the diaphysis enlarge and then die, causing the surrounding cartilage matrix to calcify.
   • This calcified cartilage then deteriorates, leaving behind cavities.
3. The Periosteal Bud Invades the Cavities, and Spongy Bone Forms:
   • A periosteal bud (a collection of blood vessels, nerves, red marrow elements, osteogenic cells, and osteoclasts) invades the internal cavities.
   • Osteoclasts break down the calcified cartilage debris.
   • Osteoblasts begin to secrete osteoid over the calcified cartilage remnants, forming early spongy bone (trabeculae).
   • This region in the diaphysis is called the primary ossification center.
4. The Diaphysis Elongates and a Medullary Cavity Forms. Secondary Ossification Centers Appear in the Epiphyses:
   • The diaphysis continues to elongate as bone formation proceeds.
   • The spongy bone in the center of the diaphysis is broken down by osteoclasts, forming the medullary cavity.
   • Secondary ossification centers typically appear in one or both of the epiphyses.
5. The Epiphyses Ossify. Hyaline Cartilage Remains Only in the Epiphyseal Plates and Articular Cartilages:
   • Similar to the primary center, osteoblasts in the secondary centers begin to form spongy bone.
   • After ossification, the ends of the bone (epiphyses) consist of compact bone externally and spongy bone internally.
   • Resulting structures: The initial hyaline cartilage model is largely replaced by bone, with two significant remnants:
     • Articular cartilage: Remains on the joint surfaces of the epiphyses.
     • Epiphyseal plate (growth plate): A disc of hyaline cartilage that persists between the diaphysis and epiphysis, allowing for postnatal bone lengthening.

Postnatal Bone Growth

After birth, bones continue to grow in two main ways:

1. Interstitial Growth (Longitudinal Growth):
   • Increases the length of long bones.
   • Occurs at the epiphyseal plate (growth plate).
2. Appositional Growth (Transverse Growth):
   • Increases the thickness (width) of all bones.
   • Involves the deposition of new bone matrix by osteoblasts in the periosteum and endosteum.

Interstitial Growth (Lengthening of Long Bones)

Interstitial growth occurs within the epiphyseal plate, a hyaline cartilage structure with five distinct zones:

1. Resting (Quiescent) Zone:
   • Located closest to the epiphysis.
   • Consists of relatively inactive chondrocytes.
   • It anchors the epiphyseal plate to the bone of the epiphysis.
2. Proliferation (Growth) Zone:
   • Chondrocytes in this zone divide rapidly by mitosis.
   • New cells are pushed towards the diaphysis, lengthening the epiphyseal plate.
3. Hypertrophic Zone:
   • Older chondrocytes in this zone hypertrophy (enlarge) dramatically.
   • Their lacunae become larger, eroding the surrounding cartilage matrix.
4. Calcification Zone:
   • The surrounding cartilage matrix calcifies (hardens) due to the death of chondrocytes (nutrient deprivation).
   • The calcified cartilage matrix is then invaded by blood vessels.
5. Ossification (Osteogenic) Zone:
   • Calcified cartilage is rapidly invaded by osteoclasts, which resorb the dying chondrocytes and calcified matrix.
   • New bone is then laid down on the remaining calcified cartilage scaffolding by osteoblasts.
   • This new bone adds to the length of the diaphysis.

This process continues until late adolescence or early adulthood. At that point, chondrocyte mitosis ceases, the epiphyseal plate diminishes, and it is entirely replaced by bone, forming the epiphyseal line, signifying the end of longitudinal growth.

Appositional Growth (Thickening of All Bones)

Appositional growth results in the increase in bone width or thickness.

• Osteoblasts in the periosteum secrete new bone matrix on the external bone surface.
• Simultaneously, osteoclasts in the endosteum (lining the medullary cavity) resorb bone from the inner surface.
• This coordinated activity increases the diameter of the bone while also enlarging the medullary cavity, preventing the bone from becoming excessively heavy.

Regulation of Bone Growth (Hormones)

Several hormones play a critical role in regulating bone growth and development, particularly during childhood and adolescence:

• Growth Hormone (GH):
  • Released by the anterior pituitary gland.
  • It is the most important hormone for stimulating epiphyseal plate activity (i.e., interstitial growth) during infancy and childhood.
• Thyroid Hormone (TH):
  • Modulates the activity of growth hormone, ensuring proper proportions during growth.
• Testosterone (in males) and Estrogen (in females):
  • Puberty: Surge during adolescence, promoting the growth spurt characteristic of puberty.
  • Initially stimulate significant bone growth.**
  • Epiphyseal Plate Closure: In late adolescence or early adulthood, high levels of these hormones ultimately stimulate the complete ossification of the epiphyseal plates, leading to their closure and ending longitudinal bone growth.

Bone Remodeling

Bone is a dynamic tissue that undergoes continuous bone remodeling throughout life.

• Process: Involves a coordinated interplay between bone deposit (osteoblasts laying down new bone) and bone resorption (osteoclasts breaking down old bone).
• Location: Occurs primarily at the surfaces of both the periosteum and endosteum.
• Stimuli: The rate and location of remodeling are influenced by mechanical stresses placed upon the bone and by hormonal signals (e.g., calcium homeostasis).
• Turnover Rate: Spongy bone is completely replaced approximately every $\text{3-4}$ years, while compact bone is replaced about every $\text{10}$ years. This constant renewal ensures bone strength and integrity.
• Osteoclast Function: Osteoclasts break down bone by secreting lysosomal enzymes (to digest organic matrix) and acids (to dissolve mineral salts).
  • The dissolved matrix components (e.g., calcium and phosphate ions) are then transcytosed (transported across the cell) by the osteoclast and released into the interstitial fluid, eventually entering the bloodstream.

Calcium Homeostasis and Regulation

Calcium ($\text{Ca}^{2+}$) is an absolutely vital mineral, essential for numerous physiological processes beyond just bone structure. Therefore, the body maintains highly precise control over blood calcium levels.

• Importance of Blood Calcium: Blood calcium levels directly affect:

  • Nerve impulse transmission.
  • Muscle contraction (including cardiac muscle).
  • Blood coagulation (clotting).
  • Glandular secretion.
  • Cell membrane permeability.

• Regulation Mechanism (when blood $\text{Ca}^{2+}$ levels fall):

  1. Stimulus: Blood $\text{Ca}^{2+}$ concentration drops below homeostatic set point (hypocalcemia).
  2. Sensor/Control Center: The parathyroid glands (four small glands on the posterior surface of the thyroid gland) detect the low blood calcium.
  3. Hormone Release: The parathyroid glands release parathyroid hormone (PTH).
  4. Target Effectors: PTH primarily targets:
     • Bones: Stimulates osteoclasts to resorb bone matrix, releasing stored $\text{Ca}^{2+}$ into the blood.
     • Kidneys: Increases $\text{Ca}^{2+}$ reabsorption in the renal tubules, reducing calcium loss in urine; also promotes the activation of Vitamin D.
     • Intestines: (Indirectly, via activated Vitamin D) Increases $\text{Ca}^{2+}$ absorption from food.
  5. Result: Blood $\text{Ca}^{2+}$ levels rise back to the normal homeostatic range.

  Key Principle: The body prioritizes blood calcium homeostasis over the amount of calcium in bone. It will