Bones and Skeletal Tissues

Skeletal Cartilages

• Human skeleton initially consists of cartilage, replaced by bone, except in areas requiring flexibility.

Basic Structure, Types, and Locations

• Skeletal cartilage:

  • Made of highly resilient, molded cartilage tissue with primarily water.

  • Contains no blood vessels or nerves.

• Perichondrium:

  • Dense connective tissue surrounding cartilage.

  • Resists outward expansion and contains blood vessels for nutrient delivery.

• Cartilage Composition:

  • Chondrocytes: cells encased in lacunae within a jelly-like extracellular matrix.

• Types of Cartilage:

  • Hyaline Cartilage:

    • Provides support, flexibility, and resilience.

    • Most abundant type; contains only collagen fibers.

    • Locations: Articular (joints), costal (ribs), respiratory (larynx), nasal cartilage (nose tip).

  • Elastic Cartilage:

    • Similar to hyaline cartilage but contains elastic fibers.

    • Locations: External ear and epiglottis.

  • Fibrocartilage:

    • Contains thick collagen fibers for great tensile strength.

    • Locations: Menisci of knee; vertebral discs.

Growth of Cartilage

• Appositional Growth:

  • Cartilage-forming cells in perichondrium secrete matrix against the external face of existing cartilage.

  • New matrix laid down on the surface of cartilage.

• Interstitial Growth:

  • Chondrocytes within lacunae divide and secrete new matrix, expanding cartilage from within.

  • New matrix made within cartilage.

• Calcification of cartilage occurs during normal bone growth in youth and old age, but hardened cartilage is not the same as bone.

Functions of Bones

• Support: For body and soft organs.

• Protection: Protects brain, spinal cord, and vital organs.

• Movement: Levers for muscle action.

• Mineral and Growth Factor Storage: Calcium and phosphorus reservoir.

• Blood Cell Formation: Hematopoiesis occurs in red marrow cavities.

• Triglyceride (fat) Storage: Energy source stored in bone cavities.

• Hormone Production: Osteocalcin secreted to regulate insulin secretion, glucose levels, and metabolism.

Classification of Bones

• 206 named bones in the human skeleton.

• Axial Skeleton:

  • Long axis of the body.

  • Skull, vertebral column, rib cage.

• Appendicular Skeleton:

  • Bones of upper and lower limbs.

  • Girdles attaching limbs to the axial skeleton.

• Classification by Shape:

  • Long Bones:

    • Longer than they are wide.

    • Limb bones.

  • Short Bones:

    • Cube-shaped bones (wrist and ankle).

    • Sesamoid bones form within tendons (e.g., patella).

    • Vary in size and number.

  • Flat Bones:

    • Thin, flat, slightly curved.

    • Sternum, scapulae, ribs, most skull bones.

  • Irregular Bones:

    • Complicated shapes.

    • Vertebrae and hip bones.

Bone Structure

• Bones are organs containing various tissues: bone, nervous, cartilage, fibrous connective tissue, muscle, and epithelial cells.

• Levels of Structure:

  • Gross

  • Microscopic

  • Chemical

Gross Anatomy

• Compact Bone: Dense outer layer, smooth and solid.

• Spongy Bone:

  • Honeycomb of small, needle-like or flat pieces called trabeculae.

  • Open spaces filled with red or yellow bone marrow.

• Structure of Short, Irregular, and Flat Bones:

  • Thin plates of spongy bone (diploe) covered by compact bone.

  • Compact bone sandwiched between connective tissue membranes (periosteum and endosteum).

  • Bone marrow scattered throughout spongy bone; no defined marrow cavity.

  • Hyaline cartilage covers movable joint areas.

• Structure of Typical Long Bone:

  • Diaphysis: Tubular shaft of compact bone surrounding a central medullary cavity (filled with yellow marrow in adults).

  • Epiphyses: Bone ends consisting of compact bone externally and spongy bone internally.

    • Articular cartilage covers joint surfaces.

    • Epiphyseal line: Remnant of the epiphyseal plate (growth plate).

• Membranes:

  • Periosteum:

    • White, double-layered membrane covering external surfaces (except joints).

    • Fibrous layer: Dense irregular connective tissue with Sharpey’s fibers.

    • Osteogenic layer: Inner layer with osteogenic stem cells.

    • Contains nerve fibers, blood vessels, and nutrient foramina.

    • Anchoring points for tendons and ligaments.

  • Endosteum:

    • Delicate connective tissue membrane covering internal bone surfaces.

    • Covers trabeculae of spongy bone and lines canals.

    • Contains osteogenic cells.

• Hematopoietic Tissue (Red Marrow):

  • Found in trabecular cavities of spongy bone and diploë of flat bones (sternum).

  • Newborns: Medullary cavities and all spongy bone contain red marrow.

  • Adults: Heads of femur and humerus, flat bone diploë, and some irregular bones (hip bone).

  • Yellow marrow can convert to red marrow if anemic.

• Bone Markings:

  • Sites of muscle, ligament, and tendon attachment.

  • Areas involved in joint formation or conduits for vessels and nerves.

  • Types: Projections, depressions, and openings.

    • Projection: outward bulge of bone

    • Depression: Bowl- or groove-like cut-out.

    • Opening: Hole or canal in bone.

Microscopic Anatomy of Bone

• Cells of Bone Tissue:

  • Osteogenic cells

  • Osteoblasts

  • Osteocytes

  • Bone-lining cells

  • Osteoclasts

• Osteogenic Cells:

  • Osteoprogenitor cells, mitotically active stem cells in periosteum and endosteum.

  • Differentiate into osteoblasts or bone-lining cells.

• Osteoblasts:

  • Bone-forming cells that secrete osteoid (unmineralized bone matrix).

  • Osteoid is made up of collagen (90% of bone protein) and calcium-binding proteins.

  • Actively mitotic.

• Osteocytes:

  • Mature bone cells in lacunae that no longer divide.

  • Maintain bone matrix and act as stress/strain sensors.

  • Communicate with osteoblasts and osteoclasts for remodeling.

• Bone-Lining Cells:

  • Flat cells on bone surfaces that help maintain matrix.

  • Periosteal cells (external) and endosteal cells (internal).

• Osteoclasts:

  • Derived from hematopoietic stem cells (macrophages).

  • Giant, multinucleate cells for bone resorption (breakdown).

  • Located in resorption bays.

  • Ruffled borders increase surface area for enzyme degradation.

• Compact Bone (Lamellar Bone):

  • Osteon (Haversian system)

  • Canals and canaliculi

  • Interstitial and circumferential lamellae

• Osteon (Haversian System):

  • Structural unit of compact bone.

  • Elongated cylinder parallel to long axis of bone.

  • Lamellae: Rings of bone matrix containing collagen fibers in different directions.

  • Bone salts found between collagen fibers to withstand stress and resist twisting.

• Canals and Canaliculi:

  • Central (Haversian) canal: Runs through the core of the osteon, containing blood vessels and nerve fibers.

  • Perforating (Volkmann’s) canals: Lined with endosteum, at right angles to central canal, connecting blood vessels and nerves.

  • Lacunae: Small cavities containing osteocytes.

  • Canaliculi: Hairlike canals connecting lacunae to each other and the central canal for nutrient and waste exchange.

• Interstitial and Circumferential Lamellae:

  • Interstitial lamellae: Fill gaps between forming osteons or remnants of remodeled osteons.

  • Circumferential lamellae: Extend around the entire surface of the diaphysis, deep to periosteum and superficial to endosteum, resisting twisting.

• Spongy Bone:

  • Organized along lines of stress.

  • Trabeculae confer strength.

  • No osteons, contains irregularly arranged lamellae, osteocytes, and canaliculi.

  • Capillaries in endosteum supply nutrients.

Chemical Composition of Bone

• Organic Components:

  • Osteogenic cells, osteoblasts, osteocytes, bone-lining cells, osteoclasts, and osteoid.

  • Osteoid: Ground substance and collagen fibers, contribute to tensile strength and flexibility.

  • Resilience due to sacrificial bonds in collagen molecules, which re-form after trauma.

• Inorganic Components:

  • Hydroxyapatites (mineral salts): Calcium phosphate crystals (65% of bone mass).

  • Responsible for hardness and compression resistance.

  • Bone is half as strong as steel in resisting compression and as strong as steel in resisting tension.

Bone Development

• Ossification (osteogenesis): Bone tissue formation.

  • Formation of the bony skeleton begins in month 2 of development.

  • Postnatal bone growth occurs until early adulthood.

  • Bone remodeling and repair are lifelong.

Formation of the Bony Skeleton

• Endochondral Ossification:

  • Bone forms by replacing hyaline cartilage; called cartilage (endochondral) bones.

  • Forms most of the skeleton inferior to the base of the skull (except clavicles).

  • Begins late in month 2 of development.

  • Requires breakdown of hyaline cartilage prior to ossification.

  • Begins at the primary ossification center in the center of the shaft.

    • Blood vessels infiltrate perichondrium, converting it to periosteum.

    • Mesenchymal cells specialize into osteoblasts.

  • Five main steps:

    • Bone collar forms around the diaphysis.

    • Central cartilage calcifies, develops cavities.

    • Periosteal bud invades cavities, spongy bone forms.

    • Diaphysis elongates, medullary cavity forms, secondary ossification centers appear in epiphyses.

    • Epiphyses ossify; hyaline cartilage remains only in epiphyseal plates and articular cartilages.

• Intramembranous Ossification:

  • Bone develops from a fibrous membrane; called membrane bones.

  • Forms frontal, parietal, occipital, temporal, and clavicle bones.

  • Four major steps:

    • Ossification centers form as mesenchymal cells cluster and become osteoblasts.

    • Osteoid is secreted and calcified.

    • Woven bone forms around blood vessels, resulting in trabeculae.

    • Lamellar bone replaces woven bone, and red marrow appears.

Postnatal Bone Growth

• Long bones grow lengthwise by interstitial (longitudinal) growth of the epiphyseal plate.

• Bones increase thickness through appositional growth.

• Bones stop growing during adolescence; some facial bones continue to grow slowly.

• Interstitial growth requires the presence of epiphyseal cartilage in the epiphyseal plate

• Epiphyseal plate maintains constant thickness – Rate of cartilage growth on one side balanced by bone replacement on other

• Epiphyseal plate consists of five zones:

  • Resting (quiescent) zone

  • Proliferation (growth) zone

  • Hypertrophic zone

  • Calcification zone

  • Ossification (osteogenic) zone

• Growth in Length of Long Bones

  • Resting (quiescent) zone

    • Area of cartilage on epiphyseal side of epiphyseal plate that is relatively inactive

  • Proliferation (growth) zone

    • Area of cartilage on diaphysis side of epiphyseal plate that is rapidly dividing

    • New cells formed move upward, pushing epiphysis away from diaphysis, causing lengthening

  • Hypertrophic zone

    • Area with older chondrocytes closer to diaphysis

    • Cartilage lacunae enlarge and erode, forming interconnecting spaces

  • Calcification zone

    • Surrounding cartilage matrix calcifies; chondrocytes die and deteriorate

  • Ossification zone

    • Chondrocyte deterioration leaves long spicules of calcified cartilage at epiphysis-diaphysis junction

    • Spicules are then eroded by osteoclasts and are covered with new bone by osteoblasts

    • Ultimately replaced with spongy bone

    • Medullary cavity enlarges as spicules are eroded

• Near end of adolescence, chondroblasts divide less often

• Epiphyseal plate thins, then is replaced by bone

• Epiphyseal plate closure occurs when epiphysis and diaphysis fuse

• Bone lengthening ceases

  • Females: occurs around 18 years of age

  • Males: occurs around 21 years of age

• Growth in Width (Thickness)

  • Growing bones widen as they lengthen through appositional growth – Can occur throughout life

  • Bones thicken in response to increased stress from muscle activity or added weight

  • Osteoblasts beneath periosteum secrete bone matrix on external bone

  • Osteoclasts remove bone on endosteal surface

  • Usually more building up than breaking down which leads to thicker, stronger bone that is not too heavy

Hormonal Regulation of Bone Growth

• Growth hormone: Stimulates epiphyseal plate activity in infancy and childhood.

• Thyroid hormone: Modulates growth hormone activity.

• Testosterone (males) and estrogens (females) at puberty: Promote adolescent growth spurts and epiphyseal plate closure.

Bone Remodeling

• 5-7% of bone mass is recycled each week.

  • Spongy bone replaced ~ every 3-4 years.

  • Compact bone replaced ~ every 10 years.

• Bone remodeling: bone deposit and resorption at periosteum and endosteum surfaces.

• Remodeling units: Packets of adjacent osteoblasts and osteoclasts coordinate the process.

Bone Resorption

• Function of osteoclasts.

  • Dig depressions or grooves as they break down matrix

  • Secrete lysosomal enzymes and protons (H+) that digest matrix

  • Acidity converts calcium salts to soluble forms

• Osteoclasts also phagocytize demineralized matrix and dead osteocytes

  • Digested products are transcytosed across cell and released into interstitial fluid and then into blood

  • Once resorption is complete, osteoclasts undergo apoptosis

• Osteoclast activation involves PTH (parathyroid hormone) and immune T cell proteins

Bone Deposit

• New bone matrix deposited by osteoblasts.

• Osteoid seam: Band of unmineralized bone matrix.

• Calcification front: Transition zone between osteoid seam and mineralized bone.

• Trigger for deposit not confirmed but may include:

  • Mechanical signals

  • Increased concentrations of calcium and phosphate ions for hydroxyapatite formation

  • Matrix proteins that bind and concentrate calcium

  • Appropriate amount of enzyme alkaline phosphatase for mineralization

Control of Remodeling

• Controlled by genetic factors and two control loops:

  • Hormonal controls: Negative feedback loop for blood Ca^{2+} levels.

    • Calcium functions in nerve transmission, muscle contraction, blood coagulation, gland and nerve secretions, and cell division.

    • 99% of 1200–1400 gms of calcium are found in bone.

    • Intestinal absorption of Ca^{2+} requires vitamin D.

  • Parathyroid Hormone (PTH):

    • Produced by parathyroid glands in response to low blood calcium levels

      • Stimulates osteoclasts to resorb bone

      • Calcium is released into blood, raising levels

      • PTH secretion stops when homeostatic calcium levels are reached

  • Calcitonin:

    • Produced by parafollicular cells of thyroid gland in response to high levels of blood calcium levels

      • Effects are negligible, but at high pharmacological doses it can lower blood calcium levels temporarily

  • Response to mechanical stress: Wolf's law

    • Leptin: Hormone released by adipose tissue that may play role in bone density regulation by inhibiting osteoblasts

    • Serotonin: Neurotransmitter that regulates mood and sleep; also interferes with osteoblast activity. It may inhibit bone turnover after a meal, so bone calcium is locked in when new calcium is flooding into bloodstream

Response to Mechanical Stress

• Bones reflect stresses they encounter; bones are stressed when weight bears on them or muscles pull on them.

• Wolf’s law: Bones grow or remodel in response to demands placed on them.

  • Stress is usually off center, so bones tend to bend.

  • Handedness results in thicker, stronger bone of the corresponding upper limb.

  • Curved bones are thickest where most likely to buckle.

  • Trabeculae form trusses along lines of stress.

  • Large, bony projections occur where heavy, active muscles attach.

  • Bones of fetus and bedridden people are featureless because of lack of stress.

• Mechanical stress causes remodeling by producing electrical signals when bone is deformed.

  • Compressed and stretched regions are oppositely charged.

• Hormonal controls determine whether and when remodeling occurs in response to changing blood calcium levels, but mechanical stress determines where it occurs.

Bone Repair

• Fractures are breaks; during youth, most fractures result from trauma, while in old age, most result from bone thinning.

Fracture Classification

• Position of bone ends after fracture:

  • Nondisplaced: Ends retain normal position.

  • Displaced: Ends are out of normal alignment.

• Completeness of break:

  • Complete: Broken all the way through.

  • Incomplete: Not broken all the way through.

• Whether skin is penetrated:

  • Open (compound): Skin is penetrated.

  • Closed (simple): Skin is not penetrated.

• Described by location, external appearance, and nature of break.

Fracture Treatment and Repair

• Treatment involves reduction, the realignment of broken bone ends.

  • Closed reduction: Physician manipulates to correct position.

  • Open reduction: Surgical pins or wires secure ends.

• Immobilization by cast or traction is needed for healing.

• Repair involves four major stages:

  • Hematoma formation

  • Fibrocartilaginous callus formation

  • Bony callus formation

  • Bone remodeling

• Hematoma Formation:

  • Torn blood vessels hemorrhage, forming a mass of clotted blood called a hematoma.

  • Site is swollen, painful, and inflamed.

• Fibrocartilaginous Callus Formation:

  • Capillaries grow into hematoma.

  • Phagocytic cells clear debris.

  • Fibroblasts secrete collagen fibers to span the break and connect broken ends.

  • Fibroblasts, cartilage, and osteogenic cells begin reconstruction of bone.

  • Mass of repair tissue is called fibrocartilaginous callus.

• Bony Callus Formation:

  • New trabeculae appear in fibrocartilaginous callus within one week.

  • Callus is converted to a bony (hard) callus of spongy bone.

  • Bony callus formation continues for about 2 months until a firm union forms.

• Bone Remodeling:

  • Begins during bony callus formation and continues for several months.

  • Excess material on diaphysis exterior and within medullary cavity is removed.

  • Compact bone is laid down to reconstruct shaft walls.

  • Final structure resembles original structure; responds to mechanical stressors.

Bone Disorders

• Imbalances between bone deposit and bone resorption underlie nearly every disease that affects the human skeleton.

• Three major bone diseases:

  • Osteomalacia and rickets

  • Osteoporosis

  • Paget’s disease

Osteomalacia and Rickets

• Osteomalacia:

  • Bones poorly mineralized; osteoid is produced, but calcium salts are not adequately deposited, resulting in soft, weak bones.

  • Pain upon bearing weight.

• Rickets (osteomalacia of children):

  • Results in bowed legs and other bone deformities because bone ends are enlarged and abnormally long.

  • Cause: vitamin D deficiency or insufficient dietary calcium.

Osteoporosis

• Bone resorption exceeds deposit; matrix remains normal, but bone mass declines.

• Spongy bone of spine and neck of femur most susceptible; vertebral and hip fractures common.

• Risk Factors:

  • Aged, postmenopausal women (30% of women aged 60–70 years and 70% by age 80).

  • Men are less prone due to protection by the effects of testosterone.

  • Insufficient exercise, poor diet, smoking, genetics, hormone-related conditions, and consumption of alcohol or certain medications.

• Treatments:

  • Calcium, vitamin D supplements, weight-bearing exercise, and hormone replacement therapy (controversial).

  • Bisphosphonates decrease osteoclast activity and number.

  • Denosumab: Monoclonal antibody that reduces fractures and improves bone density.

• Prevention:

  • Plenty of calcium in diet in early adulthood, reduced consumption of carbonated beverages and alcohol, and plenty of weight-bearing exercise.

Paget’s Disease

• Excessive and haphazard bone deposit and resorption cause bone to grow fast and develop poorly (Pagetic bone).

• Very high ratio of spongy to compact bone and reduced mineralization; usually occurs in spine, pelvis, femur, and skull.

• Rarely occurs before age 40; cause unknown (possibly viral).
  Treatment includes calcitonin and bisphosphonates.

Developmental Aspects of Bone

• Embryonic skeleton ossifies predictably, so fetal age is easily determined from X rays or sonograms.

• Most long bones begin ossifying by 8 weeks, with primary ossification centers developed by week 12.

• At birth, most long bones are ossified, except at epiphyses; epiphyseal plates persist through childhood and adolescence.

• At ~ age 25, all bones are completely ossified, and skeletal growth ceases.

Age-Related Changes in Bone

• In children and adolescents, bone formation exceeds resorption; males tend to have greater mass than females.

• In young adults, bone formation and resorption are balanced.

• In adults, bone resorption exceeds formation.

• Bone density changes are largely determined by genetics.

• Bone mass, mineralization, and healing ability decrease with age starting in the fourth decade; bone loss is greater in whites and in females. Bones of skull are exception.