Bones - Anatomy & Physiology

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Bone comprises the structure of the skeletal system and provides lever arms for locomotion. Bone also plays important roles in maintaining mineral homeostasis as well as providing the environment for hematopoesis in marrow.

Horse Skeleton - Copyright Nottingham

Development of Bone and Cartilage

Osteogenesis
- Intramembranous Ossification
  - Forms the flat bones of skull and mandible
  - No cartilaginous precursor: mesenchyme forms bone directly
    - Mesenchyme condenses, differentiates to pre-osteoblasts, then osteoblasts
    - Osteoblasts synthesize osteoid (collagen and proteoglycans)
    - Mineralization and Bone Spicule formation (spicules produce spongy bone)
    - Appositional Growth: laid down on the exterior (vs interior) surface of developing bone
  - Increasing association with blood vessels
  - Bone Marrow formed by mesenchyme between bone and blood vessels
- Endochondral Ossification
  - Responsible for embryonic bone formation as well as growth in length
  - Via cartilaginous precursor:
    - Mesenchyme condenses to form bone outline
    - Core cells differentiate to chondrocytes and begin secreting cartilage matrix
    - Peripheral condensation forms perichondrium
    - Interstitial (length) and Appositional (width) growth
    - Central cells in developing diaphysis mature and hypertrophy
    - Matrix surrounding most mature chondrocytes calcifies
    - Perichondrium differentiates to osteoblasts
  - Capillary invasion to central core, forming trabecular bone

Growth plate (Image sourced from Bristol Biomed Image Archive with permission)

Bone Growth and Remodeling
- Short bones: endochondral ossification continues in diaphysis until only cartilage rim remains
- Long bones: secondary center of ossification develops in epiphyses
  - Epiphyseal Growth Plate: transverse disc of cartilate between the two ossification centers, allows longitudinal growth to continue to maturity, then closes
  - Cartilage of epiphyseal growth plate is divided into: (from right to left on the magnified image)
    - - Resting (reserve) zone
    - - Proliferative zone
    - - Hypertrophic zone
- Primary bone has not yet been remodelled
  - Contains less mineral and more randomly arranged collagen fibers, trabecular organization
- Remodelling occurs by Haversian canals
  - Osteoclasts dig out canal, followed by blood vessel invasion
  - Concentric lamellae laid down
  - Phased resorption happens concurrently

Types of Bone

Long Bone
- Found in the limbs and act as levers for locomotion
- An elongated diaphysis (shaft) and two epiphyses (ends), each of which encases a center for ossification

Short Bone
- Found in places of articulation, such as the carpus and tarsus
- All dimensions are relatively equal, generally signifying one center of ossification

Flat Bone
- Found in the skull, pelvic girdle, and scapula
- Expand in two directions, with a broad surface for attachment of large muscle masses and protection of underlying structures

Sesamoid Bones
- Eg. Patella, Navicular bone
- Found within tendons, where they change direction over prominences that would otherwise cause damage
- Form synovial joints with major bones with which they are in contact
- Also serve to displace tendon from the axis of the joint, increasing leverage exerted by the muscle

Splanchnic Bones
- Develop in soft organs remote from skeletal connection: eg. os penis

Pneumatic Bones
- Excavated to contain air spaces, such as the skull in the instance of paranasal sinuses, and the post-cranial skeleton of birds

Composition of Bone

Histological structure of bone (Courtesy of RVC Histology images)

Microscopic bone (Courtesy of RVC Histology images)

Bone is a hard, highly specialised connective tissue
Consists of interconnected cells embedded in a calcified, collagenous matrix
Living, dynamic, responsive tissue, growing and remodelling throughout life

Bone is comprised of:

Matrix:
- Osteoid: Organic component
  - Uncalcified, homogeneous substance, Stains light pink with H&E
  - "Type I Collagen" (90%), which resists tension
  - Bone-specific proteins(10%): Osteonectin, Osteopontin, Osteocalcin
- Mineral: Inorganic component, provides rigidity
  - Crystalline lattice of calcium phosphate and calcium carbonate
  - Also contains Mg, Mn, Zn, Cu, Na, F
  - Accounts for 65% of bone

Cells:
- Osteoblasts: single layer of mesenchymal cells which synthesize bone extracellular matrix (osteoid)
  - When active, appear plump and cuboidal, with basophilic cytoplasm
    - Cell membranes are rich in alkaline phosphatase (ALP)
    - Possibly involved in pumping calcium across membranes
    - Promoted by growth factors
    - Have receptors for PTH: contract in response -> provide space for osteoclasts to attach
  - When inactive - less cytoplasm -> flattened
- Osteocytes: osteoblasts embedded in their own matrix; reside within lacunae and are interconnected via channels forming canaliculi
  - Canaliculi create connections to form a huge neural-like junctional organization
  - Contact osteoblasts and each other with cytoplasmic processes
  - Reach through canaliculi in mineralised bone matrix
  - Regulate composition of bone fluid
- Osteoclasts: giant (multinucleate [[monocytes]]) cells which act to resorb bone ECM
  - Histologically:
    - Large, often multinucleated cells
    - Acidophilic cytoplasm
  - Derived from haematopoietic stem cells
  - Sit in bone surface depression - Howship's lacuna
  - Respond to vitamin D by increasing their numbers and activity (parathyroid independent)
  - Responsible for bone resorption
    - Firstly dissolve mineral followed by collagen, using brush border
    - Do not have receptors for PTH
    - Have receptors for calcitonin
    - Involute their brush border in response
- Osteoblasts, osteocytes, chondroblasts and chondrocytes are derived from stromal fibroblastic system (osteoprogenitor cells); osteoclasts from haematopoietic system

Organization of Bone

Normal progression is from woven bone to lamellar bone, even in pathology, except for canine craniomandibular osteopathy and hypervitaminosis D, where lamellar bone is replaced by woven bone
Woven bone:
- "Random weave" which is only a normal feature in the foetus
- Coarse collagen fibres
- Later removed by osteoclasts and replaced by lamellar bone
- In adults it is a sign of a pathological condition (e.g. fracture, inflammation, neoplasia)
Lamellar bone:
- Orderly layers which are much stronger than woven bone
- Fine collagen fibres in concentric or parallel laminae
- Two main types:
  - Compact bone (cortical)
    - Sheath covers external surface of long bone, thicker in shaft and thins over epiphyses
    - Comprised of thin lamallae in a series of concentric tubes arranged around small central canals (collectively known as an osteone)
    - Forms 80% of total bone mass
    - Consists of cells and interstitial substance - 30% ossein (type of collagen) and 70% minerals, especially calcium phosphate
    - Forms the shell of long bone shafts - contain Haversian systems
  - Cancellous bone (spongy or trabecular)
    - Stacks of parallel or concentrically stacked sheets arranged as rods, plates, and arches
    - In vertebrae, flat bones and forms the hematopoeitic center of epiphyses of long bones
    - Contains no Haversian systems
Laminar bone
- Formed on periosteal surface of diaphysis
- Accommodates rapid growth of large dogs and farm animals
- Plates of woven bone from within the periosteum
- Concentric plates
- As it forms, it fuses with the bone surface

Periosteum and blood supply

Periosteum:
- Specialised sheath of connective tissue covering bone except at the articular surfaces
- Loosely attached except at tendon insertions and boney prominences (associated with major blood vessels penetrating bone)
- Histologically:
  - Outer layer - fibrous for support
  - Inner layer - osteogenic
- Rich supply of nerves and lymph vessels
- Nutrient, metaphyseal, periosteal arteries
- Normal flow of blood from medulla to periosteum due to higher pressures in medulla
- Young animals have greater blood supply
Endosteum lines the marrow cavity
Medullary Cavity and Cancellous Interstitium: bone marrow storage and production
- Red Marrow: richly vascularized, gelatinous tissue with hematopoeitic properties found abundantly in young animals
- Yellow Marrow: fat infiltration converts red marrow to yellow, causing hematopoeitic properties to dwindle

Biomechanics of Bone

Bone growth and maintenance of normal structure are directly related to mechanical forces
Mechanical forces generate bioelectrical potentials (piezoelectricity)
- These potentials strengthen bone
- Inactivity reduces the potentials -> bone loss

Wolff's Law: Bone architecture adapts in response to the loads applied upon it according to mathematical laws
- Load: the external force placed on a structure, F
- Strain: the proportional change in the structure's dimensions
- Stress: the internal forces resisting the change in dimension caused by the load
The normality of bone architecture and appearance is directly related to its loading history
Cells use strain as a stimulus to adjust mass and architecture according to load
Resorption and osteogenesis happen concurrently to maintain bone integrity
- Mediated by two hormones:
  - Parathyroid hormone (PTH)
    - Produced by chief cells in the parathyroid glands in response to decreased serum calcium
    - In response, osteoclasts increase in number and resorb mineralised matrix - increase Ca in blood
  - Calcitonin
    - Produced by C-cells in the thyroid glands in response to increased serum calcium
    - Inhibits osteoclasts

In neonates:
- Bone growth predominates
- Modelling is important
In adults:
- Formation of bone is balanced by resorption - remodelling
- Continues throughout life under the influence of hormones and mechanical pressure
- Bone resorption may exceed formation in pathological states (hormonal, trauma, nutritional) or in old age and disuse

Structure and Function of Cartilage

Function: resist compression, provide resilience and support at sites where flexibility is desired
Structure:
- Chondrocytes: reside within lacunae within ECM synthesizing matrix
- Type II Collagen (except fibrocartilage)
- Proteoglycans with associated glycosaminoglycans
  - Continually turned over
  - The most vulnerable component of cartilage
  - Decresed proteoglycan -> loss of lubrication -> collagen disruption -> frays, clefts, fibrillation, ulcers, exposure of bone, eburnation, +/- osteophytes and joint mice
- Hyaluronic acid
- 75% Water
- Avascular: nutrients/waste move via diffusion
- Perichondrium is composed of two layers:
  - Fibrous: outer, dense irregular connective tissue
  - Chondrogenic: inner, flattened cells that differentiate to chondrocytes

Types of Cartilage

Hyaline Cartilage

Most abundant in the body: glassy, translucent sheen
Normally blue-white, smooth with moist surface, Turns yellow and becomes thinner in old age
Found in nose, trachea, bronchi, ventral ends of ribs and sternal attachmont
Surrounded by perichondrium
At sites of articulation, providing resilient frictionless surface that resists compression
Found at epiphyseal growth plates

Elastic Cartilage

Yellow appearance
found in auricular cartilage, larynx, eustacian tube, and epiglottis
Surrounded by perichondrium
Resiliance with added flexibility

Fibrocartilage

More collagen (Type I) and less proteglycans than hyaline
Resists high tensional strain
Often in transition with hyaline
Found in intervertebral discs, tendon/ligament attachment to bone, joint menisci, and articular surface of some joints (such as the temperomandibular)
NO perichondrium

Links

Bone and Cartilage Pathology