Module 6: Bone Tissue and the Skeletal System

Basic Structure of Cartilage

  • Cartilage tissue is molded to fit a particular function.
  • Primarily consists of water, allowing it to spring back to its original shape after compression.
  • Contains no blood vessels (avascular).
  • Contains chondrocytes located in small cavities called lacunae within the extracellular matrix.
  • Surrounded by perichondrium:
    • Dense connective tissue.
    • Contains blood vessels for nutrient delivery, which limits the size of the cartilage.
    • Functions as a girdle around the cartilage that resists outward expansion.

Types of Cartilage

  • Hyaline cartilage:
    • Provides support, flexibility, and resilience.
    • Composed of collagen fibers only.
    • Most abundant type of cartilage.
    • Found in articular (between two bones), costal (ribs), respiratory, and nasal cartilage.
  • Elastic cartilage:
    • Similar to hyaline cartilage but contains elastic fibers.
    • Found in the external ear and epiglottis.
  • Fibrocartilage:
    • Contains thick collagen fibers, offering great tensile strength.
    • Found in the menisci of the knee and vertebral discs.

Growth of Cartilage

  • The flexible matrix accommodates mitosis.
  • Calcification of cartilage:
    • Occurs during normal bone growth in youth and old age.
    • Hardens, but the calcified cartilage is explicitly not bone.
  • Appositional growth:
    • Cells in the perichondrium secrete matrix against the external face of existing cartilage.
  • Interstitial growth:
    • Chondrocytes divide and secrete new matrix, expanding cartilage from within.

Classification of Bones

  • The skeleton is divided into two major groups:
    • Axial skeleton:
      • Forms the long axis of the body.
      • Includes the skull, vertebral column, and rib cage.
    • Appendicular skeleton:
      • Includes the bones of the upper and lower limbs.
      • Girdles attach the limbs to the axial skeleton.
  • The human skeleton consists of $206$ named bones.

Classification of Bones by Shape

  • Long bones:
    • Longer than they are wide.
    • Examples: Limb bones, wrist bones, and ankle bones.
  • Short bones:
    • Cube-shaped bones.
    • Examples: Wrist and ankle bones.
    • Sesamoid bones: A type of short bone embedded within tendons.
      • Example: The patella (kneecap).
      • Can vary in size and number among different individuals.
  • Flat bones:
    • Generally thin, flattened, and often slightly curved (not explicitly stated in the transcript but implied by other sources for this category).
    • Examples: Cranial bones, sternum, scapulae, ribs.
  • Irregular bones:
    • Bones with complicated shapes.
    • Examples: Vertebrae, coxal (hip) bones.

Main Functions of Bones

  • Support: For the body and soft organs.
  • Protection: For the brain, spinal cord, and vital internal organs.
  • Movement: Act as levers for muscle action.
  • Mineral and growth factor storage:
    • A reservoir for calcium and phosphorus ions.
    • A reservoir for growth factors.
  • Blood cell formation (Hematopoiesis): Occurs in the red marrow cavities of certain bones.
  • Triglyceride (fat) storage: Yellow marrow serves as an energy source through stored fat.
  • Hormone production:
    • Example: Osteocalcin, a hormone that regulates bone formation.
    • Osteocalcin also protects against obesity, glucose intolerance, and diabetes mellitus.

Bone as an Organ and Its Structure Levels

  • Bones are organs containing different tissue types:
    • Bone (osseous) tissue, nervous tissue, cartilage, fibrous connective tissue, muscle tissue, and epithelial cells (found in blood vessels).
  • We examine bone structure at three levels:
    • Gross Anatomy
    • Microscopic Anatomy
    • Chemical Anatomy
  • Two different bone textures:
    • Compact bone: The dense outer layer, which is smooth and solid.
    • Spongy bone: A honeycomb of flat pieces of bone, called trabeculae, located deep to the compact bone.

Structure of Short, Irregular, and Flat Bones

  • Consist of thin plates of spongy bone covered by compact bone.
  • These plates are sandwiched between connective tissue membranes: the periosteum (outer) and endosteum (inner).
  • They do not possess a distinct shaft (diaphysis) or epiphyses.
  • Bone marrow is found throughout the spongy bone, but there is no marrow cavity.
  • Hyaline cartilage covers articular surfaces where these bones form joints.

Structure of a Typical Long Bone

  • Diaphysis:
    • The tubular shaft, forming the long axis of the bone.
    • Composed of compact bone surrounding a medullary cavity.
    • In adults, the medullary cavity contains yellow marrow (fat).
  • Epiphysis:
    • The bone ends, which are usually broader than the shaft.
    • Composed of external compact bone with internal spongy bone.
    • Articular cartilage covers the articular surfaces.
  • Epiphyseal Line:
    • Located at the juncture of the diaphysis and epiphysis.
    • A remnant of childhood bone growth at the epiphyseal plate.
  • Membranes: Includes the Periosteum and Endosteum.

Membranes: Periosteum

  • A white, double-layered membrane.
  • Covers external bone surfaces, except for joint surfaces.
  • Outer fibrous layer:
    • Composed of dense irregular connective tissue.
    • Sharpey's fibers: Collagen fibers that secure the periosteum to the bone matrix.
  • Osteogenic layer:
    • Abuts the bone surface.
    • Contains primitive stem cells, called osteogenic cells.
  • Many nerve fibers and blood vessels pass through the shaft via the periosteum.
  • Serves as anchoring points for tendons and ligaments.

Membranes: Endosteum

  • A delicate connective tissue membrane covering internal bone surfaces.
  • Covers the trabeculae of spongy bone.
  • Lines the canals that pass through compact bone.
  • Contains osteogenic cells that can differentiate into other bone cells (osteoblasts, osteoclasts).

Hematopoietic Tissues in Bones: Red Bone Marrow

  • In adults, red bone marrow is primarily found within:
    • Trabecular cavities of spongy bone.
    • Diploë (spongy bone) of flat bones (e.g., the sternum).
  • In newborns, red marrow is found in virtually all medullary cavities and spongy bone.
  • Adult long bones have little red marrow, primarily located in the heads of the femur and humerus.
  • Red marrow in the diploë and some irregular bones (like hip bones) is the most active site of hematopoiesis.
  • Yellow marrow can convert to red marrow if necessary, such as under anemic conditions.

Markings Found on Bone

  • Bone markings are features on the external surfaces of bones that serve specific purposes:
    • Sites of muscle, ligament, and tendon attachment.
    • Joint surfaces.
    • Projections: Usually indicate stresses created by muscle pull or modifications related to joints.
    • Depressions:
    • Openings: Allow nerves and blood vessels to pass through.

Bone Markings: Projections That Are Sites of Muscle and Ligament Attachment

  • Tuberosity: A large, rounded projection that may be roughened (e.g., ischial tuberosity).
  • Crest: A narrow ridge of bone, usually prominent (e.g., iliac crest).
  • Trochanter: A very large, blunt, irregularly shaped process (found only on the femur; e.g., greater trochanter).
  • Line: A narrow ridge of bone, less prominent than a crest (e.g., intertrochanteric line).
  • Tubercle: A small, rounded projection or process (e.g., adductor tubercle).
  • Epicondyle: A raised area on or above a condyle (e.g., medial epicondyle).
  • Spine: A sharp, slender, often pointed projection (e.g., ischial spine, spinous process).
  • Process: Any bony prominence.

Bone Markings: Projections That Help to Form Joints

  • Head: A bony expansion carried on a narrow neck (e.g., head of the femur).
  • Facet: A smooth, nearly flat articular surface (e.g., facets on vertebrae).
  • Condyle: A rounded articular projection (e.g., occipital condyle).
  • Ramus: An armlike bar of bone (e.g., ramus of the mandible).

Bone Markings: Depressions and Openings for Passage of Blood Vessels and Nerves

  • Groove: A furrow.
  • Fissure: A narrow, slit-like opening (e.g., inferior orbital fissure).
  • Foramen: A round or oval opening through a bone (e.g., foramen magnum).
  • Notch: An indentation at the edge of a structure.

Bone Markings: Other

  • Meatus: A canal-like passageway (e.g., external acoustic meatus).
  • Sinus: A cavity within a bone, filled with air and lined with mucous membrane (e.g., frontal sinus).
  • Fossa: A shallow, basin-like depression in a bone, often serving as an articular surface (e.g., olecranon fossa).

Microscopic Anatomy of Bone: Cells of Bone Tissue

  • Osteogenic cells (osteoprogenitor cells):
    • Mitotically active stem cells found in the periosteum and endosteum.
    • Differentiate into osteoblasts or bone-lining cells when stimulated.
  • Osteoblasts:
    • Bone-forming cells that are mitotically active.
    • Secrete unmineralized bone matrix, called osteoid.
    • Osteoid primarily consists of collagen (approximately $90\%$ of bone's organic material) and calcium-binding proteins.
  • Osteocytes:
    • Mature bone cells located in lacunae.
    • Monitor and maintain the bone matrix.
    • Act as stress or strain sensors, responding to and communicating mechanical stimuli.
    • These cells communicate with osteoblasts and osteoclasts, facilitating bone remodeling.
  • Bone-lining cells:
    • Flat cells found on bone surfaces.
    • Believed to help maintain the bone matrix.
    • Periosteal cells: Line the external bone surface.
    • Endosteal cells: Line the internal bone surface.
  • Osteoclasts:
    • Giant, multinucleated cells specialized for bone resorption (breakdown).
    • Derived from hematopoietic stem cells, which also produce macrophages.
    • When active, they rest in a resorption bay (Howship's lacuna).
    • Possess a ruffled border that increases surface area for enzymatic degradation of bone and seals off the area from the surrounding matrix.

Microscopic Anatomy of Bone: Compact (Lamellar) Bone

  • The structural unit of compact bone is called an Osteon (or Haversian System).
    • An osteon is an elongated cylinder parallel to the long axis of the bone.
    • Composed of hollow tubes of bone matrix known as lamellae.
    • Collagen fibers within adjacent lamellae rings run in different directions, allowing the osteon to withstand stress and resist twisting forces.
  • Canals and Canaliculi:
    • Central (Haversian) canal: Runs through the core of each osteon and contains blood vessels and nerve fibers.
    • Perforating (Volkmann's) canals:
      • Canals lined with endosteum, running at right angles to the central canal.
      • Contain blood vessels and nerves from the periosteum, medullary cavity, and central canal.
    • Lacunae: Small cavities that house the osteocytes.
    • Canaliculi: Hairlike canals that connect lacunae to each other and to the central canal.
      • Canaliculi Formation: Osteoblasts secrete bone matrix while maintaining contact with each other and with osteocytes via cell projections with gap junctions. As the matrix hardens, these cells become trapped, forming the canaliculi.
      • Function: Canaliculi allow for communication between osteocytes and permit nutrient and waste transport from one osteocyte to another throughout the entire osteon.
  • Other Lamellae Types:
    • Interstitial lamellae:
      • Incomplete lamellae that are not part of a complete osteon.
      • They fill the gaps between forming osteons or are remnants of osteons cut by bone remodeling.
    • Circumferential lamellae:
      • Just deep to the periosteum but superficial to the endosteum.
      • Extend around the entire surface of the diaphysis.
      • Help resist the twisting of the long bone.

Microscopic Anatomy of Bone: Spongy Bone

  • Also referred to as cancellous bone.
  • Appears poorly organized when compared to compact bone.
  • Comprises trabeculae (honeycomb-like network):
    • Trabeculae align along lines of stress to help resist it.
    • Unlike compact bone, spongy bone does not contain osteons.
    • Contains irregularly arranged lamellae and osteocytes that are interconnected by canaliculi.
  • Nutrients are supplied by capillaries in the endosteum.

Blood and Nerve Supply to Bone

  • Spongy bone and the medullary cavity receive nutrients from arteries that pass through the compact bone.
  • Arteries enter through the nutrient foramen, which are small openings in the diaphysis.
  • Nerves follow the same path into the bone as the blood vessels.

Chemical Composition of Bone

Organic Components

  • Includes various bone cells (osteogenic cells, osteoblasts, osteocytes, bone-lining cells, and osteoclasts) and osteoid.
  • Osteoid:
    • Constitutes $1/3$ of the organic bone matrix, secreted by osteoblasts.
    • It is an unmineralized, organic matrix that serves as a precursor to mature, calcified bone.
    • Made of ground substance (proteoglycans and glycoproteins) and collagen fibers.
    • Collagen fibers:
      • Contribute significantly to the structural integrity of bone.
      • Provide tensile strength and flexibility.
      • The resilience of bone is due to sacrificial bonds within or between collagen molecules.
        • These bonds stretch and break easily on impact to dissipate energy and prevent bone fracture.
        • If no additional trauma occurs, these bonds can reform.
        • This mechanism is analogous to crumple zones in cars, which absorb impact energy.

Inorganic Components

  • Hydroxyapatites (mineral salts):
    • Constitute approximately $65\%$ of bone by mass.
    • Primarily composed of tiny calcium phosphate crystals deposited in and around collagen fibers.
    • Responsible for the hardness and resistance to compression that characterizes bone.
    • Mathematically, bone is about half as strong as steel in resisting compression but is as strong as steel in resisting tension.

Bone Development (Ossification/Osteogenesis)

  • Ossification (osteogenesis) is the process of bone tissue formation.
  • It involves:
    • The formation of the bony skeleton, beginning in the $2^{nd}$ month of development.
    • Postnatal bone growth, which continues until early adulthood.
    • Bone remodeling and repair, occurring throughout the entire lifespan of an individual.
  • Endochondral ossification:
    • Bone forms by replacing a hyaline cartilage model, requiring its prior breakdown.
    • Bones formed this way are called cartilage (endochondral) bones.
    • This process forms the majority of the skeleton, starting in the $2^{nd}$ month of development.
  • Intramembranous ossification:
    • Bone develops directly from a fibrous membrane.
    • Bones formed this way are called membrane bones.
    • This process forms flat bones, such as the clavicle and most cranial bones (e.g., frontal, parietal, occipital, temporal).

Endochondral Ossification Process

  1. Primary ossification center appears: Begins in the center of the cartilage model's shaft.
  2. Bone collar formation: Blood vessel infiltration of the perichondrium converts it into a periosteum, and the underlying mesenchymal cells differentiate into osteoblasts. These osteoblasts secrete bone matrix, forming a bone collar around the diaphysis of the cartilage model.
  3. Cartilage calcification and cavitation: The central cartilage in the diaphysis calcifies, and the encased chondrocytes die and their matrix deteriorates, forming cavities.
  4. Periosteal bud invasion: A periosteal bud (containing a nutrient artery and vein, nerve fibers, red marrow elements, osteogenic cells, and osteoclasts) invades these cavities, leading to the formation of spongy bone.
  5. Diaphysis elongation and medullary cavity formation: The diaphysis elongates as bone formation continues, and osteoclasts break down the newly formed spongy bone to create a medullary cavity.
  6. Epiphysis ossification: Secondary ossification centers appear in the epiphyses, and the process is similar to primary ossification, except spongy bone remains and no medullary cavity forms in the epiphyses.

Intramembranous Ossification Process

  • This process forms the frontal, parietal, occipital, and temporal bones, as well as the clavicles.
  1. Formation of fibrous membrane: Begins with fibrous connective tissue membranes formed by mesenchymal cells.
  2. Ossification centers appear: Mesenchymal cells cluster and differentiate into osteoblasts within the fibrous membrane, forming an ossification center.
  3. Osteoid secretion: Osteoblasts secrete osteoid, trapping themselves within the matrix as osteocytes.
  4. Woven bone and periosteum formation: As osteoid is laid down, it forms a network of trabeculae (woven bone). Vascularized mesenchymal tissue condenses on the external surface of the woven bone, forming the periosteum.
  5. Lamellar bone replacement: Lamellar (compact) bone replaces the woven bone just deep to the periosteum, and red marrow appears in the trabecular cavities.

Postnatal Bone Growth

  • Interstitial (longitudinal) growth:
    • Responsible for the increase in length of long bones.
    • Requires the continued presence of epiphyseal cartilage.
    • The epiphyseal plate maintains a constant thickness, as the rate of cartilage growth on one side is balanced by bone replacement on the other.
    • Concurrent remodeling of the epiphyseal ends occurs to maintain proper proportions.
    • This growth is the result of five defined zones within the epiphyseal cartilage:
      • Resting (quiescent) zone
      • Proliferation (growth) zone
      • Hypertrophic zone
      • Calcification zone
      • Ossification (osteogenic) zone
  • Appositional growth:
    • Responsible for the increase in bone thickness (or width).

Interstitial Growth: Detailed Zones

  • Resting (quiescent) zone: Cartilage on the epiphyseal side of the epiphyseal plate, relatively inactive.
  • Proliferation (growth) zone:
    • Cartilage on the diaphysis side of the epiphyseal plate.
    • Chondrocytes rapidly divide, pushing the epiphysis away from the diaphysis, which results in bone lengthening.
  • Hypertrophic zone:
    • Older chondrocytes closer to the diaphysis enlarge, and their lacunae erode, leading to interconnecting spaces.
  • Calcification zone:
    • The surrounding cartilage matrix calcifies.
    • Chondrocytes die and deteriorate.
  • Ossification (osteogenic) zone:
    • Chondrocyte deterioration leaves long spicules of calcified cartilage at the epiphysis-diaphysis junction.
    • These spicules are eroded by osteoclasts and covered with new bone by osteoblasts.
    • Ultimately, the calcified cartilage is replaced with spongy bone.

Interstitial Growth: Epiphyseal Plate Closure

  • Near the end of adolescence, chondroblasts in the epiphyseal plate divide less often.
  • The epiphyseal plate thins and is eventually replaced by bone.
  • Epiphyseal plate closure:
    • Bone lengthening ceases because it requires the presence of cartilage, which is no longer there.
    • The bone of the epiphysis and diaphysis fuses together.
    • In females, this typically occurs around $18$ years of age.
    • In males, this typically occurs around $21$ years of age.

Appositional Growth

  • Allows lengthening bones to widen.
  • Occurs throughout life.
  • Mechanism:
    • Osteoblasts beneath the periosteum secrete bone matrix on the external bone surface.
    • At the same time, osteoclasts remove bone on the endosteal surface (inner lining).
    • There is usually more bone building up than breaking down, which results in a thicker, stronger bone without making it too heavy.

Hormonal Regulation of Bone Growth

  • Growth hormone: The most important hormone for stimulating epiphyseal plate activity during infancy and childhood.
  • Thyroid hormone: Modulates the activity of growth hormone and ensures proper bone proportions.
  • Testosterone (in males) and estrogen (in females) at puberty:
    • Promote adolescent growth spurts.
    • Ultimately end longitudinal growth by inducing epiphyseal plate closure.
  • Excesses or deficits of any of these hormones can lead to abnormal skeletal growth.

Bone Homeostasis

  • The skeletal system is dynamic, recycling $5-7\%$ of bone mass each week.
  • Turnover rates:
    • Spongy bone is replaced approximately every $3-4$ years.
    • Compact bone is replaced about every $10$ years.
  • Older bone becomes more brittle because calcium salts crystallize, making it fracture more easily.
  • Bone homeostasis consists of two main processes: bone remodeling and bone repair.
  • Remodeling involves both bone deposit and bone resorption, occurring at the surfaces of both the periosteum and endosteum.

Bone Deposit

  • Evidence of new matrix deposit by osteoblasts.
  • Osteoid seam: An unmineralized band of bone matrix.
  • Calcification front: An abrupt transition zone between the osteoid seam and the older, mineralized bone.
  • Signals: The exact signals initiating bone deposit are not fully determined, but mechanical signals are involved.
  • Requirements for mineralization:
    • Sufficient concentrations of calcium and phosphate ions in the endosteal cavity for hydroxyapatite formation.
    • Matrix proteins that bind and concentrate calcium.
    • The enzyme alkaline phosphatase, which is crucial for mineralization.

Bone Resorption: Osteoclasts

  • Osteoclasts dig depressions or grooves as they break down the bone matrix.
  • They secrete lysosomal enzymes that digest the organic matrix.
  • They also secrete hydrogen ions ($H^+$), which increase the acidity in the resorption bay to convert calcium salts into soluble forms.
  • Osteoclasts then phagocytize the demineralized matrix and dead osteocytes.
  • Through transcytosis, the breakdown products are released into the interstitial fluid and then into the blood.
  • Once their resorption work is complete, osteoclasts undergo apoptosis (programmed cell death).
  • Their activation involves the hormone PTH (Parathyroid Hormone) and T-cell secreted proteins.

Control of Bone Remodeling

  • Bone remodeling occurs continuously but is tightly regulated by genetic factors and two main control loops:
    • Responses to mechanical and gravitational forces acting on the skeleton.
    • A negative feedback loop for $Ca^{2+}$ homeostasis in the blood. This loop primarily controls blood calcium levels, not bone integrity directly.

Physiological Importance of Calcium

  • Calcium is essential for numerous physiological functions:
    • Nerve impulse transmission.
    • Muscle contraction.
    • Blood coagulation (clotting).
    • Secretion by glands and nerve cells.
    • Cell division.
  • The human body contains approximately $1200-1400$ grams of calcium.
    • About $99\%$ of this calcium exists in bone minerals.
    • Intracellular calcium constitutes about $0.9\%$ of total calcium but is usually stored in modified organelles, maintaining precise cytoplasmic concentrations.
  • The amount of calcium in the blood is tightly regulated within a narrow range (9−11 mg/dL9-11 \text{ mg/dL}), which constitutes about $0.1\%$ of total body calcium.
  • Intestinal absorption of calcium requires Vitamin D metabolites, which is why milk sold in stores is often fortified with Vitamin D.
  • Adequate dietary intake of calcium is required.

Hormonal Control of Blood Calcium

  • Parathyroid Hormone (PTH):
    • Produced by the parathyroid glands.
    • Acts to remove calcium from bone, releasing it into the blood, regardless of the bone's structural integrity.
    • This is the primary hormone regulating acute changes in blood calcium levels.
  • Calcitonin:
    • Produced by parafollicular cells (C cells) of the thyroid gland.
    • In high (pharmacological) doses, it can temporarily lower blood calcium levels, but its physiological role in humans is minor.
  • Calcium and Phosphate homeostasis are intricately linked.

Imperative Nature of Calcium Homeostasis

  • Even minute changes in blood calcium levels can lead to severe issues:
    • Neuromuscular problems:
      • Hyperexcitability if calcium levels are too low (hypocalcemia).
      • Non-responsiveness (lethargy and weakness) if calcium levels are too high (hypercalcemia).
    • Hypercalcemia: Sustained high blood calcium levels can lead to:
      • Deposits of calcium salts in blood vessels and/or kidneys, which can interfere with their normal function.

Other Hormones That Impact Bone Density

  • Leptin:
    • A hormone released by adipose tissue (fat cells).
    • Plays a role in bone density regulation, particularly by inhibiting osteoblasts in animals.
  • Serotonin:
    • A neurotransmitter primarily known for regulating mood and sleep.
    • Most serotonin is made in the gut and secreted into the blood after eating.
    • It interferes with osteoblast activity, potentially reducing bone formation.
    • Sustained use of serotonin reuptake inhibitors (SSRIs), such as Prozac, has been linked to lower bone density.

Responses to Mechanical Stress on Bones

  • Bones are highly adaptive, reflecting the stresses they encounter.
  • Long bones are typically thickest midway along the diaphysis, which is precisely where bending stresses are the greatest.
  • Mechanism of stress:
    • Bones are stressed when weight bears on them or when muscles pull on them.
    • These forces are usually off-center, causing bones to bend.
    • Bending results in compression on one side of the bone while stretching the other side.

Wolff’s Law

  • Principle: Wolff's Law states that bones grow or remodel in response to the demands placed on them.
  • Explanations and examples of Wolff's Law:
    • Handedness: The bones of the upper limb in the dominant hand (e.g., right arm for a right-handed person) are typically thicker and stronger due to greater stress.
    • Curved bones: These bones are thickest where they are most likely to buckle under stress.
    • Trabeculae: In spongy bone, trabeculae form trusses that align precisely along lines of stress, providing optimal strength.
    • Bony projections: Large, prominent bony projections (e.g., muscle attachment sites) occur where heavy, active muscles attach, reflecting the significant pull exerted by these muscles.
    • Featureless bones: The bones of a fetus or bedridden individuals (who experience minimal mechanical stress) tend to be featureless and lack the prominent markings seen in active individuals.

Causes of Bone Remodeling

  • Mechanical stress:
    • Determines where remodeling occurs within the bone.
    • Electrical signals produced by deforming bone (compressed and stretched regions are oppositely charged) may also trigger remodeling.
    • Fluid flows within canaliculi, carrying nutrients and wastes, also appear to provide remodeling stimuli to osteocytes.
  • Hormonal influences:
    • Primarily determine whether and when remodeling occurs, primarily in response to changing blood calcium levels.

Bone Fractures

  • Fractures are classified based on several criteria:
    • Location of the break.
    • External appearance (whether skin is broken).
    • Nature of the break.
  • Position of bone ends after fracture:
    • Non-displaced fracture: The bone ends retain their normal position.
    • Displaced fracture: The bone ends are out of normal alignment.
  • Completeness of the break:
    • Complete fracture: The bone is broken all the way through.
    • Incomplete fracture: The bone is not broken all the way through.
  • Whether skin is penetrated:
    • Open (compound) fracture: The skin is penetrated by the bone ends.
    • Closed (simple) fracture: The skin is not penetrated by the bone ends.

Common Types of Fractures

  • Comminuted fracture: The bone fragments into three or more pieces. This type is particularly common in the aged, whose bones are more brittle.
  • Compression fracture: The bone is crushed. Common in porous bones (e.g., osteoporotic bones) subjected to extreme trauma, such as a fall.
  • Spiral fracture: A ragged break occurs when excessive twisting forces are applied to a bone. This is a common sports fracture.
  • Epiphyseal fracture: The epiphysis separates from the diaphysis along the epiphyseal plate. Tends to occur where cartilage cells are dying and calcification of the matrix is occurring, making it weak.
  • Depressed fracture: The broken bone portion is pressed inward, typical of skull fractures.
  • Greenstick fracture: The bone breaks incompletely, much like a green twig breaks; only one side of the shaft breaks, and the other side bends. Common in children, whose bones have relatively more organic matrix and are more flexible than those of adults.

Fracture Treatment

  • Reduction: The realignment of broken bone ends.
    • Closed reduction: A physician manipulates the bone fragments into correct position externally.
    • Open reduction: Surgical intervention is required to secure the bone ends with pins or wires.
  • Immobilization: The bone must be held stationary to allow healing. The duration and method of immobilization depend on the severity of the break, the specific bone broken, and the age of the patient.

Stages of Bone Repair

  1. Hematoma Forms:
    • Torn blood vessels hemorrhage at the fracture site.
    • A blood clot (hematoma) forms, filling the gap between the broken bone ends.
    • The site becomes swollen, painful, and inflamed.
  2. Fibrocartilaginous Callus Forms:
    • Within days, capillaries grow into the hematoma.
    • Phagocytic cells (such as macrophages) clear debris from the injury site.
    • Fibroblasts secrete collagen fibers that span the break, connecting the broken bone ends.
    • Fibroblasts, cartilage cells (chondroblasts), and osteogenic cells begin the reconstruction of the bone.
    • Chondroblasts create a cartilage matrix of repair tissue, and osteoblasts form spongy bone within this matrix.
    • Together, this mass of repair tissue is called the fibrocartilaginous callus.
  3. Bony Callus Forms:
    • Within one week, new trabeculae of spongy bone begin to appear in the fibrocartilaginous callus.
    • The fibrocartilaginous callus is gradually converted into a bony (hard) callus of spongy bone.
    • Approximately two months later, a firm union between the bone fragments forms.
  4. Bone Remodeling Occurs:
    • This stage begins during bony callus formation and continues for several months.
    • Excess material on the diaphysis exterior and within the medullary cavity is removed.
    • Compact bone is laid down to reconstruct the shaft walls.
    • The final structure closely resembles the original bone because it continues to respond to the same mechanical stressors, leading to optimal structural integrity.

Homeostatic Imbalances of Bone

  • Osteomalacia:
    • Description: Bones are poorly mineralized, often due to inadequate calcium salts.
    • Symptoms: Soft, weak bones, leading to pain upon bearing weight.
    • Rickets (osteomalacia of children):
      • Symptoms: Characterized by bowed legs and other bone deformities; bone ends become enlarged and abnormally long.
      • Cause: Generally a nutrient deficiency of Vitamin D or calcium.
  • Osteoporosis:
    • Description: Bone resorption (breakdown) outpaces bone deposition (formation), leading to reduced bone mass and increased fragility.
    • Most susceptible areas: The spongy bone of the spine and the neck of the femur.
    • Common: Vertebral and hip fractures are prevalent.

Risk Factors for Osteoporosis

  • Sex hormones: Sex hormones (estrogen in women, testosterone in men) maintain normal bone health and density. As their secretion wanes with age, especially during menopause in women, it can lead to osteoporosis.
    • Most often affects aged, post-menopausal women, with approximately $30\%$ of individuals between the ages of $60-70$ and $70\%$ by age $80$ affected.
    • Men are affected to a lesser extent, but risk increases in conditions like prostate cancer when taking androgen-suppressing drugs.
  • Petite body form.
  • Insufficient exercise: Lack of weight-bearing exercise fails to stress bones, which is crucial for maintaining bone density (Wolff's Law).
  • Diet poor in calcium and proteins.
  • Smoking.
  • Hormone-related conditions:
    • Hyperthyroidism.
    • Low blood levels of thyroid-stimulating hormone (TSH).
    • Diabetes mellitus.

Treating Osteoporosis

  • Traditional treatments:
    • Calcium supplements.
    • Vitamin D supplements.
    • Weight-bearing exercise.
    • Hormone replacement therapy (HRT): Can slow bone loss but typically does not reverse it. It is controversial due to an increased risk of heart attack, stroke, and breast cancer. Estrogenic compounds found in soy may serve as a natural substitute.
  • Bisphosphonates: A class of drugs that decrease osteoclast activity and number, which can partially reverse bone loss, especially in the spine.
  • Selective estrogen receptor modulators (SERMs): These mimic estrogen's beneficial effects on bone without targeting breast and uterus tissues.
  • Statins: Although primarily used for lowering cholesterol, some statins have also been shown to increase bone mineral density.
  • Denosumab: A monoclonal antibody that improves bone density in the elderly and reduces fractures in men with prostate cancer.

Preventing Osteoporosis

  • Ensure a plenty of calcium in the diet during early adulthood to build peak bone mass.
  • Reduce carbonated beverage and alcohol consumption, as these can leach minerals from bone, decreasing bone density.
  • Engage in plenty of weight-bearing exercises, which increases bone mass above normal for a buffer against age-related bone loss.

Other Bone Conditions: Paget’s Disease

  • Description: Characterized by excessive and haphazard (uncontrolled) bone deposition and resorption.
  • Result: Bone is made fast and poorly, leading to what is referred to as "Paget bone."
  • Characteristics: Paget bone has a very high ratio of spongy to compact bone and reduced mineralization, making it weak and deformed.
  • Location: Usually occurs in the spine, pelvis, femur, and skull.
  • Age of onset: Rarely occurs before the age of $40$.
  • Cause: The cause is unknown, but there is some indication it may be triggered by certain viruses.
  • Treatment: Includes calcitonin (to slow bone resorption) and bisphosphonates (to inhibit osteoclast activity).

Age-Related Changes in Bone and Developmental Aspects

  • Children and adolescents: During these growth phases, bone formation significantly exceeds bone resorption.
  • Young adults: Bone formation and resorption are generally in balance, though males typically display greater bone mass than females.
  • Genetics: Bone density changes over a lifetime are largely determined by genetic factors. For instance, the gene for Vitamin D's cellular docking mechanism can influence bone mass early in life and the risk of osteoporosis as age progresses.
  • Aging (after age $40$): Bone mass, mineralization, and healing ability all decrease with age.
    • Exception: The bones of the skull tend to be less affected by age-related bone loss.
    • Bone loss is generally greater in females and in individuals of white ethnicity.
    • Treatments: Electrical stimulation and/or daily ultrasound treatments have been shown to hasten bone repair in older individuals.

Developmental Aspects of Bones

  • The embryonic skeleton ossifies predictably, allowing fetal age to be easily determined from sonograms and X-rays.
  • Most long bones begin to ossify by $8$ weeks of embryonic development.
  • Primary ossification centers are typically established by $12$ weeks.
  • At birth, most long bones are well ossified, with the exception of their epiphyses, which remain cartilaginous.
  • By approximately age $25$, nearly all bones are completely ossified, and skeletal growth ceases.