Bones and Bone Tissue: Structure, Function, and Physiology

Bones and Bone Tissue

Introduction to the Skeletal System

The skeletal system is a complex organ system that includes bones, joints, and supporting tissues. Bones are the main organs, with adults typically having 206 bones. Each bone is composed of bone (osseous) tissue, dense regular and irregular connective tissue, and bone marrow.

Functions of the Skeletal System

• Protection: Bones such as the skull, sternum, and ribs protect vital organs.

• Mineral Storage and Acid-Base Homeostasis: Bones store minerals (calcium, phosphorus, magnesium) essential for electrolyte and acid-base balance.

• Blood Cell Formation: Red bone marrow is the site of hematopoiesis (blood cell production).

• Fat Storage: Yellow bone marrow stores triglycerides in adipocytes.

• Movement: Bones serve as attachment sites for muscles, enabling movement at joints.

• Support: The skeleton provides structural support for the body.

Bone Structure

Classification by Shape

• Long Bones: Longer than wide (e.g., humerus, femur).

• Short Bones: About as long as wide (e.g., wrist, ankle bones).

• Flat Bones: Thin and broad (e.g., skull, pelvis).

• Irregular Bones: Complex shapes (e.g., vertebrae).

• Sesamoid Bones: Small, oval-shaped, within tendons (e.g., patella).

Structure of a Long Bone

• Periosteum: Outer membrane of dense irregular connective tissue with blood vessels and nerves.

• Perforating Fibers: Collagen anchors attaching periosteum to bone matrix.

• Diaphysis: Shaft containing the medullary (marrow) cavity lined by endosteum and filled with marrow.

• Epiphyses: Ends of the bone, filled with red marrow and covered with articular cartilage (hyaline cartilage).

• Compact Bone: Dense outer layer resisting compression and twisting.

• Spongy (Cancellous) Bone: Inner honeycomb-like structure housing bone marrow.

• Epiphyseal Lines: Remnants of the growth plate (hyaline cartilage) in adults.

Structure of Short, Flat, Irregular, and Sesamoid Bones

These bones share similarities with long bones but have fewer structures. In flat bones, the spongy bone is called diploë. Some skull bones contain sinuses to reduce weight.

Blood and Nerve Supply to Bone

• Supplied by blood vessels in the periosteum and nutrient arteries entering through the nutrient foramen.

• Short, flat, irregular, and sesamoid bones receive blood mainly from periosteal vessels.

Red and Yellow Marrow

• Red Marrow: Site of hematopoiesis; abundant in children, limited to certain bones in adults.

• Yellow Marrow: Contains adipocytes and blood vessels; increases with age.

The Extracellular Matrix of Bone

Inorganic Matrix

• Comprises ~65% of bone weight.

• Mainly calcium and phosphorus in the form of hydroxyapatite crystals ($\mathrm{Ca_{10}(PO_4)_6(OH)_2}$), providing strength and resistance to compression.

• Also contains bicarbonate, potassium, magnesium, and sodium salts.

Organic Matrix (Osteoid)

• Comprises ~35% of bone weight.

• Contains collagen fibers, proteoglycans, glycosaminoglycans, glycoproteins, and bone-specific proteins (e.g., osteocalcin).

• Collagen resists torsion and tensile forces; osteocalcin organizes the inorganic matrix.

Bone Cells

• Osteoblasts: Derived from osteogenic cells; build bone by secreting organic matrix and aiding inorganic matrix formation.

• Osteocytes: Mature osteoblasts trapped in lacunae; maintain ECM and signal bone remodeling.

• Osteoclasts: Large, multinucleated cells from bone marrow; break down bone ECM via bone resorption.

Osteopetrosis

Osteopetrosis ("marble bone disease") results from defective osteoclasts, leading to increased but brittle bone mass. Infantile forms can be fatal due to nerve entrapment and marrow failure; adult forms cause pain and fractures.

Histology of Bone

Compact Bone

• Composed of osteons (Haversian systems) with concentric lamellae, central canals, lacunae, and canaliculi.

• Interstitial and circumferential lamellae strengthen bone; perforating (Volkmann) canals connect osteons.

Spongy Bone

• Consists of trabeculae with lamellae, lacunae, and canaliculi but lacks central canals.

• Blood supply comes from bone marrow vessels.

Bone Formation: Ossification

Primary vs. Secondary Bone

• Primary (Woven) Bone: Immature, irregular collagen, little inorganic matrix.

• Secondary (Lamellar) Bone: Mature, organized lamellae, higher inorganic content.

Types of Ossification

• Intramembranous Ossification: Forms flat bones (e.g., skull, clavicles) from mesenchymal membrane; spongy bone forms first.

• Endochondral Ossification: Forms most bones below the head from a hyaline cartilage model; compact bone forms first.

Steps of Intramembranous Ossification

1. Osteoblasts develop in the primary ossification center from mesenchymal cells.

2. Osteoblasts secrete organic matrix, which calcifies; trapped osteoblasts become osteocytes.

3. Osteoblasts lay down trabeculae of early spongy bone; some mesenchyme becomes periosteum.

4. Osteoblasts in periosteum lay down early compact bone; matrix is remodeled.

Steps of Endochondral Ossification

1. Chondroblasts in perichondrium differentiate into osteoblasts.

2. Osteoblasts build a bone collar; internal cartilage calcifies and chondrocytes die.

3. Osteoblasts replace calcified cartilage with early spongy bone; secondary ossification centers and medullary cavity develop.

4. Remaining cartilage is replaced by bone; epiphyses finish ossifying; cartilage remains at epiphyseal plates and articular surfaces.

Comparison Table: Intramembranous vs. Endochondral Ossification

Feature	Intramembranous	Endochondral
Bone Types	Flat bones (skull, clavicle)	Long, short, irregular bones
Model	Mesenchymal membrane	Hyaline cartilage
Order of Bone Formation	Spongy bone first	Compact bone first

Bone Growth

Longitudinal Growth (Length)

Occurs at the epiphyseal plate, which has five zones:

1. Zone of Reserve Cartilage

2. Zone of Proliferation (chondrocyte division)

3. Zone of Hypertrophy and Maturation (chondrocyte enlargement)

4. Zone of Calcification (chondrocyte death, matrix calcifies)

5. Zone of Ossification (osteoblasts build bone)

Appositional Growth (Width)

• Osteoblasts in the periosteum lay down new circumferential lamellae, thickening the bone.

• Osteoclasts enlarge the medullary cavity as bone thickens.

Hormonal Regulation of Bone Growth

• Growth Hormone: Increases chondrocyte mitosis, osteogenic cell activity, and osteoblast activity.

• Testosterone: Increases appositional growth and mitosis; accelerates epiphyseal plate closure.

• Estrogen: Similar effects as testosterone but less pronounced; earlier epiphyseal plate closure.

Bone Remodeling

Overview

Bone remodeling is a continuous process involving bone deposition (by osteoblasts) and bone resorption (by osteoclasts). It maintains calcium homeostasis, repairs bone, replaces old bone, and adapts bone to stress.

Bone Deposition

• Osteoblasts secrete organic matrix and vesicles containing calcium, ATP, and enzymes, initiating calcification.

Bone Resorption

• Osteoclasts secrete hydrogen ions (dissolve inorganic matrix) and enzymes (break down organic matrix).

Factors Influencing Bone Remodeling

• Mechanical Stress: Compression and tension stimulate deposition; pressure stimulates resorption.

• Hormones: Testosterone promotes deposition; estrogen inhibits osteoclasts.

• Age: Hormone levels decline, reducing bone formation.

• Nutrient Intake: Calcium, vitamin D, K, C, and protein are essential for healthy bone remodeling.

Calcium Homeostasis

• Parathyroid Hormone (PTH): Increases blood calcium by stimulating bone resorption, increasing intestinal absorption, and reducing urinary loss.

• Calcitonin: Decreases blood calcium by stimulating bone deposition (less potent in adults).

Bone Repair

Steps of Fracture Healing

1. Hematoma formation: Blood fills the fracture gap, bone cells die.

2. Soft callus formation: Fibroblasts and chondroblasts produce connective tissue and cartilage.

3. Bone callus formation: Osteoblasts lay down primary bone.

4. Remodeling: Primary bone is replaced by secondary bone.

Types of Fractures

Type	Description
Simple (Closed)	Skin and tissue remain intact
Compound (Open)	Skin and tissue are damaged
Transverse	Fracture is perpendicular to bone's long axis
Spiral	Fracture spirals around the bone
Comminuted	Bone is shattered into multiple pieces
Compression	Bone is crushed (often in vertebrae)
Greenstick	Bone breaks on one side, bends on the other (common in children)
Epiphyseal Plate	Fracture involves the growth plate

Treatment of Fractures

• Closed Reduction: Bone ends are aligned without surgery.

• Open Reduction: Surgical fixation with plates, wires, or screws.

Clinical Correlations

• Osteoporosis: Inadequate inorganic matrix leads to brittle bones and increased fracture risk. Prevention includes adequate calcium/vitamin D, exercise, and medications.

• Achondroplasia: Most common cause of dwarfism due to abnormal cartilage growth; results in short limbs and characteristic features.

• Gigantism and Acromegaly: Excess growth hormone before (gigantism) or after (acromegaly) epiphyseal plate closure causes abnormal bone growth.