Chapter 6 The Skeletal System: Bone Tissue

Introduction to Bone and the Skeletal System

• Definition of Bone: Bone is classified as an organ because it is composed of several different types of tissues working together. These tissues include:

  • Bone (osseous) tissue.

  • Cartilage.

  • Dense connective tissue.

  • Adipose tissue.

  • Nervous tissue.

• The Skeletal System: This system is constituted by the entire framework of bones along with their associated cartilages.

Functions of the Skeletal System

1. Support: It provides a structural framework for the body by supporting soft tissues and providing attachment points for the tendons of most skeletal muscles.

2. Protection: It protects the most important internal organs from injury. For example, the cranial bones protect the brain, and the rib cage protects the heart and lungs.

3. Assistance in Movement: Most skeletal muscles attach to bones; when they contract, they pull on bones to produce movement.

4. Mineral Homeostasis (Storage and Release): Bone tissue stores several minerals, particularly calcium and phosphorus, which contribute to the strength of the bone. Bone can release minerals into the blood to maintain critical mineral balances.

5. Blood Cell Production (Hemopoiesis): Within certain bones, a connective tissue called red bone marrow produces red blood cells, white blood cells, and platelets.

6. Triglyceride Storage: Yellow bone marrow consists mainly of adipose cells, which store triglycerides. These stored lipids are a potential chemical energy reserve.

Anatomy and Structure of Long Bones

A typical long bone, such as the humerus, consists of the following parts:

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

• Epiphyses: The proximal and distal ends of the bone at the joints.

• Metaphyses: The regions between the diaphysis and the epiphyses. In a growing bone, each metaphysis contains an epiphyseal (growth) plate, a layer of hyaline cartilage that allows the diaphysis of the bone to grow in length. When growth stops, the cartilage is replaced by bone and is then known as the epiphyseal line.

• Articular Cartilage: A thin layer of hyaline cartilage covering the part of the epiphysis where the bone forms an articulation (joint) with another bone. It reduces friction and absorbs shock.

• Periosteum: A tough connective tissue sheath and its associated blood supply that surrounds the bone surface wherever it is not covered by articular cartilage.

  • Outer fibrous layer: Composed of dense irregular connective tissue.

  • Inner osteogenic layer: Consists of cells.

  • Perforating (Sharpey's) fibers: Thick bundles of collagen that extend from the periosteum into the bone extracellular matrix to attach the periosteum to the bone.

• Medullary Cavity (Marrow Cavity): A hollow, cylindrical space within the diaphysis that contains fatty yellow bone marrow and numerous blood vessels in adults.

• Endosteum: A thin membrane that lines the medullary cavity. It contains a single layer of bone-forming cells and a small amount of connective tissue.

Histology of Bone Tissue

• Extracellular Matrix: Bone contains an abundant extracellular matrix that surrounds widely separated cells. The composition of the matrix is:

  • $15\%$ water.

  • $30\%$ collagen fibers.

  • $55\%$ crystallized mineral salts (the most abundant is calcium phosphate).

• Types of Cells in Bone Tissue:

  • Osteoprogenitor Cells: Unspecialized bone stem cells derived from mesenchyme. They are the only bone cells to undergo cell division; the resulting cells develop into osteoblasts.

  • Osteoblasts: Bone-building cells. They synthesize and secrete collagen fibers and other organic components needed to build the extracellular matrix of bone tissue, and they initiate calcification. As they become surrounded by their own secretions, they become trapped and turn into osteocytes.

  • Osteocytes: Mature bone cells. These are the main cells in bone tissue and maintain its daily metabolism, such as the exchange of nutrients and wastes with the blood.

  • Osteoclasts: Huge cells derived from the fusion of as many as 50 monocytes (a type of white blood cell). They are concentrated in the endosteum. The plasma membrane of an osteoclast is deeply folded into a ruffled border on the side that faces the bone surface. Here, they release powerful lysosomal enzymes and acids that digest the protein and mineral components of the underlying bone extracellular matrix (resorption).

Microscopic Anatomy: Compact and Spongy Bone

• Compact Bone Tissue:

  • Provides protection and support and resists the stresses produced by weight and movement.

  • Osteons (Haversian Systems): The repeating structural units of compact bone. Each osteon consists of concentric lamellae (circular plates of mineralized extracellular matrix) arranged around an osteonic (Haversian) canal.

  • Lacunae: Small spaces between the concentric lamellae which contain osteocytes.

  • Canaliculi: Tiny channels radiating in all directions from the lacunae, filled with extracellular fluid and slender fingerlike processes of osteocytes. They connect lacunae with one another and with the central canals, forming an intricate miniature system of interconnected canals throughout the bone.

  • Interosteonic (Volkmann’s or Perforating) Canals: Canals through which blood vessels and nerves from the periosteum penetrate the compact bone.

  • Interstitial Lamellae: Areas between neighboring osteons which contain lamellae that are fragments of older osteons that have been partially destroyed during bone rebuilding or growth.

  • Circumferential Lamellae: Lamellae arranged around the entire outer and inner circumference of the shaft of a long bone (external and internal).

• Spongy (Cancellous) Bone Tissue:

  • Does not contain osteons. It is always located in the interior of a bone, protected by a covering of compact bone.

  • Trabeculae: An irregular lattice of thin columns of bone. Within each trabecula are concentric lamellae, osteocytes in lacunae, and canaliculi.

  • The spaces between the trabeculae of some bones are filled with red bone marrow (which produces blood cells) and yellow bone marrow (adipose tissue) in others.

  • Spongy bone is lightweight, which reduces the overall weight of a bone, and the trabeculae support and protect the red bone marrow.

Blood and Nerve Supply of Bone

• Periosteal Arteries: Accompanied by nerves, these enter the diaphysis through numerous Interosteonic (Volkmann's) canals and supply the periosteum and outer part of the compact bone. They are accompanied by periosteal veins.

• Nutrient Artery: A large artery that enters the center of the diaphysis through an opening called the nutrient foramen. Once inside the medullary cavity, it divides into proximal and distal branches that supply the inner part of compact bone tissue and the spongy bone tissue and red bone marrow as far as the epiphyseal plates. Nutrient veins exit via the same canal.

• Metaphyseal Arteries: Enter the metaphyses of a long bone and, together with the nutrient artery, supply the red bone marrow and bone tissue of the metaphyses.

• Epiphyseal Arteries: Enter the epiphyses of a long bone and supply the red bone marrow and bone tissue of the epiphyses.

• Nerves: The periosteum is rich in sensory nerves, some of which carry pain sensations, which is why bone damage (like a fracture) is very painful.

Bone Formation: Ossification (Osteogenesis)

Ossification is the process by which bone forms. It occurs in four situations:

1. Initial formation of bones in an embryo and fetus.

2. Growth of bones during infancy, childhood, and adolescence until their adult sizes are reached.

3. Remodeling of bone (replacement of old bone by new bone tissue throughout life).

4. Repair of fractures (breaks in bones) throughout life.

Methods of Bone Formation:

• Intramembranous Ossification: Bone forms directly within mesenchyme, which is arranged in sheetlike layers that resemble membranes. This occurs in the flat bones of the skull, most of the facial bones, mandible, and the medial part of the clavicle.

  1. Development of the ossification center: Osteoblasts secrete organic extracellular matrix.

  2. Calcification: Calcium and other mineral salts are deposited; the matrix calcifies (hardens).

  3. Formation of trabeculae: Extracellular matrix develops into trabeculae that fuse to form spongy bone.

  4. Development of the periosteum: Mesenchyme at the periphery develops into the periosteum.

• Endochondral Ossification: Bone forms within hyaline cartilage that develops from mesenchyme. Most bones of the body are formed this way.

  • This process replaces cartilage with bone in the developing embryo and fetus.

  • It also occurs in the epiphyseal plates of long bones as they grow in length.

Bone Growth and Remodeling

• Growth in Thickness: Bones grow in thickness (appositional growth) due to the cooperative action of osteoblasts and osteoclasts.

  • Osteoblasts at the bone surface deposit bone extracellular matrix on the outer surface.

  • Osteoclasts in the endosteum widen the medullary cavity from within by resorbing bone. This ensures the bone becomes thicker and stronger without becoming too heavy.

• Remodeling: The ongoing replacement of old bone tissue by new bone tissue. It involves bone resorption (removal of minerals and collagen fibers from bone by osteoclasts) and bone deposition (addition of minerals and collagen fibers to bone by osteoblasts).

Fracture and Repair of Bone

A fracture is any break in a bone. The repair process involves three phases in four specific steps:

1. Reactive Phase: An early inflammatory phase.

   • Step 1: Formation of fracture hematoma. Blood vessels crossing the fracture line are broken, and a mass of blood (usually clotted) forms around the site of the fracture within 6 to 8 hours.

2. Reparative Phase: Characterized by the formation of a callus.

   • Step 2: Fibrocartilaginous (soft) callus formation. Fibroblasts from the periosteum produce collagen fibers, and cells from the periosteum develop into chondroblasts that begin to produce fibrocartilage. This takes about 3 weeks.

   • Step 3: Bony (hard) callus formation. In areas closer to well-vascularized healthy bone tissue, osteoprogenitor cells develop into osteoblasts, which begin to produce spongy bone trabeculae. The fibrocartilage is converted to spongy bone, and the callus is then referred to as a bony callus. This lasts about 3 to 4 months.

3. Bone Remodeling Phase: The final step of fracture repair.

   • Step 4: Dead portions of the original fragments of broken bone are gradually resorbed by osteoclasts. Compact bone replaces spongy bone around the periphery of the fracture.

Bone's Role in Calcium Homeostasis

Bones store $99\%$ of the body's calcium. Calcium ($Ca^{2+}$) levels in the blood are regulated by a negative feedback system.

• Low Blood Calcium Levels:

  • Receptors/Control Center: Parathyroid gland cells detect lowered $Ca^{2+}$ concentration, which increases the production of cyclic AMP. This turns on the gene for Parathyroid Hormone (PTH).

  • Output: The parathyroid glands increase the release of PTH into the blood.

  • Effectors:

    1. Osteoclasts: PTH increases the number and activity of osteoclasts, which speed up bone resorption. This releases $Ca^{2+}$ from bone into the blood.

    2. Kidneys: PTH stimulates the kidneys to retain $Ca^{2+}$ in the blood and excrete phosphate in the urine.

    3. Calcitriol: PTH stimulates the kidneys to produce calcitriol (the active form of vitamin D). Calcitriol increases the absorption of calcium from the gastrointestinal tract (intestines) into the blood.

  • Response: The blood $Ca^{2+}$ level increases, returning the body to homeostasis.

• High Blood Calcium Levels:

  • The thyroid gland secretes Calcitonin (CT), which inhibits the activity of osteoclasts, speeds up blood $Ca^{2+}$ uptake by bone, and accelerates $Ca^{2+}$ deposition into bones.

Factors Affecting Bone Growth

Minerals

• Calcium and Phosphorus: Make bone extracellular matrix hard.

• Magnesium: Helps form bone extracellular matrix.

• Fluoride: Helps strengthen bone extracellular matrix.

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

Vitamins

• Vitamin A: Needed for the activity of osteoblasts during remodeling; deficiency stunts bone growth; toxic in high doses.

• Vitamin C: Needed for synthesis of collagen (main bone protein); deficiency leads to decreased collagen production, slowing bone growth and delaying repair.

• Vitamin D (Calcitriol): Produced by kidneys; increases calcium absorption from the GI tract into blood; deficiency causes faulty calcification and slows growth. Toxic in high doses.

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

Hormones

• Growth Hormone (GH): From the anterior pituitary; stimulates production of insulin-like growth factors.

• Insulin-like Growth Factors (IGFs): From liver and bone; stimulate osteoblasts, promote protein synthesis, and increase cell division at epiphyseal plates.

• Thyroid Hormones ($T_3$ and $T_4$): From thyroid gland; stimulate osteoblasts and promote bone growth.

• Insulin: From pancreas; promotes growth by increasing synthesis of bone proteins.

• Sex Hormones (Estrogens and Testosterone):

  • Stimulate osteoblasts and promote the teenage "growth spurt."

  • Shut down growth at epiphyseal plates around age 18-21.

  • In adulthood, they slow bone resorption by osteoclasts and promote deposition by osteoblasts.

• Parathyroid Hormone (PTH): Promotes bone resorption by osteoclasts; recovers $Ca^{2+}$ from urine; promotes calcitriol formation.

• Calcitonin (CT): Inhibits bone resorption by osteoclasts.

Exercise and Aging in Bone Tissue

• Exercise: Weight-bearing activities (like walking or weightlifting) stimulate osteoblasts. This helps build thicker, stronger bones and retards the loss of bone mass that occurs with age.

• Aging:

  • From birth through adolescence, more bone is produced than is lost.

  • In young adults, the rates of deposition and resorption are about equal.

  • Bone Loss: As levels of sex hormones diminish (middle age to older adulthood), resorption by osteoclasts outpaces deposition by osteoblasts. This is particularly prevalent in post-menopausal women, leading to a decrease in bone mass and an increased risk of osteoporosis.

Homeostatic Imbalances and Disorders

• Bone Scan: A diagnostic procedure that utilizes a radioactive tracer to detect abnormalities such as bone cancer, fractures, or inflammation.

• Osteoporosis: A condition where bone resorption outpaces bone deposition, making bones porous and very brittle.

• Ricketts: A disease in children in which the bones fail to calcify, usually due to Vitamin D deficiency, leading to soft, rubbery bones that bow under weight.

• Osteomalacia: The adult equivalent of ricketts; new bone formed during remodeling fails to calcify.