Anatomy and Physiology: Bone Tissue

Functions of Bone and the Skeletal System

• Bone is a dynamic and complex organ composed of bone tissue, cartilage, dense connective tissue, adipose tissue, and nervous tissue. It is highly vascularized and undergoes continuous remodeling.

• The skeletal system includes all the bones and cartilages in the body, providing a framework that supports and protects the body's organs, and enables movement.

Functions of the Skeletal System

1. Support: Provides structural support for the body, acting as a scaffold that maintains posture and supports soft tissues.

2. Protection: Protects internal organs such as the brain (cranium), spinal cord (vertebrae), heart, and lungs (rib cage). The bony structure acts as a barrier against physical trauma.

3. Movement: Assists body movements in conjunction with muscles. Bones serve as levers, and joints act as fulcrums, allowing for a wide range of motions when muscles contract.

4. Mineral Homeostasis: Stores and releases essential minerals, most notably calcium and phosphorus, to help maintain mineral balance in the body. Bone mineral density is crucial for overall health.

5. Hemopoiesis: Participates in blood cell production. Red bone marrow found in certain bones is responsible for producing red blood cells, white blood cells, and platelets.

6. Triglyceride Storage: Stores triglycerides in adipose cells of yellow marrow. Yellow marrow, found in the medullary cavity of long bones, serves as a storage site for fats, which can be mobilized for energy.

Structure of Bone

• A long bone consists of several distinct parts:

  • Diaphysis: The bone shaft or body—a long, cylindrical main portion of the bone.

  • Epiphyses: The two ends of the bone at the joints (both proximal and distal).

  • Metaphyses: Regions between the diaphysis and epiphyses. In growing bones, this area includes an epiphyseal plate of cartilage, which is eventually replaced by bone to form the epiphyseal line.

  • Articular Cartilage: Covers both epiphyses; reduces friction and absorbs shocks at the joints. It is hyaline cartilage and lacks a perichondrium.

  • Periosteum: Connective tissue (dense irregular) surrounding the diaphysis; essential for bone growth, repair, and nutrition. It has an outer fibrous layer and an inner osteogenic layer.

  • Medullary Cavity: Hollow space within the diaphysis that contains yellow bone marrow (adipose tissue) in adults.

  • Endosteum: Thin membrane lining the medullary cavity; contains osteoblasts and osteoclasts.

Histology of Bone

• Bone contains an abundant extracellular matrix with widely separated cells. The matrix is composed of:

  • 15% water

  • 30% collagen fibers

  • 55% crystallized mineral salts.

• Mineral salts, including calcium phosphate (Ca3(PO4)2) and calcium hydroxide (Ca(OH)2), form hydroxyapatite crystals (Ca{10}(PO4)6(OH)2). These crystals provide hardness to the bone.

Bone Cells

• Osteoprogenitor Cells: Bone stem cells that differentiate into other types of cells, located in the periosteum and endosteum. They undergo cell division to produce osteoblasts.

• Osteoblasts: Bone-building cells that secrete bone matrix (collagen and ground substance); initiate calcification. They eventually become osteocytes as they get trapped in the matrix.

• Osteocytes: Mature bone cells derived from osteoblasts, located in lacunae. They maintain bone tissue and sense bone microdamage; also regulate mineral homeostasis.

• Osteoclasts: Large, multinucleated cells that remodel bones and cause them to release calcium through bone resorption. They are derived from monocytes and macrophages.

Types of Bone Tissue

• Compact Bone: Provides protection and support; strongest type, found beneath the periosteum and makes up the bulk of the diaphysis of long bones.

• Spongy Bone: Lightweight and provides tissue support; also called trabecular or cancellous bone. It is found in the epiphyses of long bones and interior of other bones, protecting red bone marrow.

Compact Bone vs. Spongy Bone

• Compact Bone:

  • Contains osteons (Haversian systems), which include:

    • Concentric bone lamellae: Rings of calcified matrix.

    • Interstitial bone lamellae: Fragments of older osteons.

    • External/internal circumferential bone lamellae: Located around the outer and inner surfaces of the bone.

  • Blood vessels are present in the central (Haversian) canal.

  • Osteocytes reside in bone lacunae connected by bone canaliculi, which allow for nutrient and waste exchange.

• Spongy Bone:

  • Consists of trabeculae (irregular lamellae with osteocytes).

  • Osteocytes reside in lacunae within the trabeculae; osteoblasts and osteoclasts are found on the surface.

  • Spaces between trabeculae contain red bone marrow in bones that produce blood cells.

Blood and Nerve Supply of Bone

• Periosteal Arteries: Enter the diaphysis through Volkmann’s canals (perforating canals), accompanied by periosteal veins. These supply the periosteum and outer compact bone.

• Nutrient Artery: Enters the center of the diaphysis through a nutrient foramen; nutrient veins exit via the same canal. This is the main blood supply to the diaphysis.

• Metaphyses and epiphyses have their own arteries and veins (epiphyseal and metaphyseal arteries and veins) that supply red bone marrow and bone tissue.

Bone Formation

• Ossification (osteogenesis) is the process of bone formation.

• Occurs in four principal situations:

  1. During embryological and fetal development

  2. When bones grow before adulthood

  3. When bones remodel (ongoing process)

  4. When fractures heal

Types of Ossification

1. Intramembranous Ossification:

   • Occurs in flat bones (e.g., skull bones, mandible, clavicle) when a connective tissue membrane is replaced by bone.

   • Involves the differentiation of mesenchymal cells into osteoblasts, which secrete bone matrix.

2. Endochondral Ossification:

   • Replaces cartilage with bone in the developing embryo and fetus; also occurs in epiphyseal plates of long bones as they grow in length.

   • Involves the formation of a cartilage model, which is then progressively replaced by bone.

Bone Growth

• Endochondral ossification also occurs in epiphyseal plates of long bones as they grow in length. The epiphyseal plate consists of four zones:

  • Zone of resting cartilage

  • Zone of proliferating cartilage

  • Zone of hypertrophic cartilage

  • Zone of calcified cartilage

• Bones thicken through the cooperative action of osteoblasts and osteoclasts (appositional growth).

  • Osteoblasts deposit bone on the outer surface, while osteoclasts widen the medullary cavity from within.

Factors Affecting Bone Growth and Remodeling

• Minerals: Calcium, phosphorus, magnesium, fluoride, manganese—critical for the formation and maintenance of bone matrix.

• Vitamins: A, C, D, K, and B12—play various roles in bone metabolism and collagen synthesis.

• Hormones:

  • IGFs (Insulin-like Growth Factors) stimulated by GH (Growth Hormone) promote bone growth by stimulating osteoblasts and protein synthesis.

  • T3 (Triiodothyronine) and T4 (Thyroxine) thyroid hormones modulate bone cell activity.

  • Sex hormones (estrogen in females, testosterone in males) stimulate osteoblast activity and promote the closure of epiphyseal plates.

Fracture and Repair of Bone

• A fracture is a break in a bone, which can be classified based on the nature and location of the break.

• Healing involves three phases in four steps:

  • Reactive Phase:

    • Early inflammatory phase with formation of a fracture hematoma (clotted blood) at the fracture site.

  • Reparative Phase:

    • Formation of a fibrocartilaginous callus first, which is a soft callus consisting of collagen fibers and cartilage.

    • Formation of a bony callus second, as osteoblasts convert the fibrocartilaginous callus into spongy bone.

  • Bone Remodeling Phase:

    • The bony callus is remodeled by osteoclasts and osteoblasts, with compact bone replacing spongy bone.

Bone's Role in Calcium Homeostasis

• Bones store 99% of the body’s calcium and also contain significant amounts of phosphorus.

• The parathyroid gland secretes parathyroid hormone (PTH) when calcium levels drop.

  • Osteoclasts are stimulated to increase bone resorption, releasing calcium and phosphate into the blood.

  • PTH stimulates the production of calcitriol (active form of Vitamin D) by the kidneys to increase calcium absorption in the intestines.

Calcium Homeostasis Mechanism

1. Stimulus: Decrease in blood calcium (Ca^{2+}) level.

2. Receptors: Parathyroid gland cells detect lowered calcium concentration.

3. Control Center: Increased production of cyclic AMP activates the parathyroid hormone gene.

4. Output: Increased release of PTH.

5. Effectors:

   • Osteoclasts increase bone resorption to release calcium and phosphate.

   • Kidneys retain Ca^{2+} in blood, excrete phosphate in urine, and produce calcitriol.

   • Intestines increase calcium absorption due to calcitriol.

6. Response: Increase in blood Ca^{2+} level, returning to homeostasis.

Exercise and Aging in Bone Tissue

• From birth through adolescence, more bone is produced than lost during remodeling, leading to an increase in bone mass and density.

• In adults, the rates of bone formation and resorption are generally the same, maintaining bone mass.

• Older individuals, especially post-menopausal women, experience a decrease in bone mass as resorption outpaces deposition, due to decreased estrogen levels.

Summary of Factors That Affect Bone Growth

• Minerals:

  • Calcium and phosphorus: Harden bone extracellular matrix, providing strength and rigidity.

  • Magnesium: Helps form bone extracellular matrix and influences bone remodeling.

  • Fluoride: Helps strengthen bone extracellular matrix and increases bone density.

  • Manganese: Activates enzymes involved in the synthesis of bone extracellular matrix.

• Vitamins:

  • Vitamin A: Needed for osteoblast activity during remodeling; deficiency stunts growth.

  • Vitamin C: Needed for collagen synthesis; deficiency decreases collagen production, slowing bone growth and delaying repair.

  • Vitamin D: Active form (calcitriol) helps build bone by increasing calcium absorption; deficiency causes faulty calcification and slows growth.

  • Vitamins K and B12: Needed for synthesis of bone proteins; deficiency leads to abnormal protein production and decreased bone density.

• Hormones:

  • Growth Hormone (GH): Promotes growth of all body tissues, including bone, by stimulating IGF production.

  • Insulin-Like Growth Factors (IGFs): Promote normal bone growth by stimulating osteoblasts and increasing protein synthesis.

  • Thyroid Hormones (T3 and T4): Promote normal bone growth by stimulating osteoblasts.

  • Insulin: Promotes normal bone growth by increasing bone protein synthesis.

  • Sex Hormones (Estrogens and Testosterone): Stimulate osteoblasts and promote growth spurts; contribute to remodeling by slowing bone resorption and promoting bone deposition.

  • Parathyroid Hormone (PTH): Promotes bone resorption by osteoclasts and enhances calcium recovery from urine.

  • Calcitonin (CT): Inhibits bone resorption by osteoclasts and lowers blood calcium levels.

• Exercise and Aging:

  • Exercise: Weight-bearing activities stimulate osteoblasts, build thicker, stronger bones, and retard bone mass loss.

  • Aging: Decreasing sex hormone levels, especially in post-menopausal women, cause bone resorption to outpace deposition, leading to decreased bone mass and increased osteoporosis risk.

Disorders: Homeostatic Imbalances

• Osteoporosis: Bone resorption outpaces formation, leading to decreased bone mass and increased susceptibility to fractures. 80% of those affected are women due to decreased estrogen levels after menopause.

• Rickets and Osteomalacia: Inadequate calcification of extracellular bone matrix, usually due to vitamin D deficiency.

  • Rickets affects children, leading to bowed legs and other skeletal deformations.

  • Osteomalacia affects adults, causing painful, tender bones and fractures with minor trauma.

Medical Terminology

• Osteoarthritis: Degeneration of articular cartilage, leading to bone-on-bone friction, pain, and reduced joint function.

• Osteomyelitis: Infection of bone, often caused by Staphylococcus aureus, leading to inflammation and bone destruction.

• Osteopenia: Reduced bone mass below normal, which is a precursor to osteoporosis.

• Osteosarcoma: Bone cancer that primarily affects osteoblasts; it is most