Bones

Bone is a rigid organ that constitutes part of vertebrate skeleton in animals. Bone constitutes of 30% of flexible matrix and 70% of bound minerals.

The bone matrix is 90-95% composed of elastic collagen fibres also known as Ossein, rest of which is just ground substance. The collagen elasticity improves fracture resistance. 

Bone matrix

The hardness and rigidity of bone is due to the presence of mineral salt in the osteoid matrix, which is a crystalline complex of calcium and phosphate (hydroxyapatite). Calcified bone contains about 25% organic matrix (2-5% of which are cells), 5% water and 70% inorganic mineral (hydroxyapatite).

The matrix is hardened by binding of inorganic salts, calcium phosphate in an arrangement known as Calcium HydroxyLapatite. 

Bone is actively constructed & remodeled throughout the life by special bone cells known as Osteoblasts and Osteoclasts.

Osteoclasts are responsible for aged bone resorption and while Osteoblasts are responsible for new bone formation.

Role Of Osteoblast in Osteoclast formation:

1. Cell to cell contact: The process happens by direct contact between the two of them. It initiates with osteoclatogenesis mainly depends on interaction between two cells.

2. Ephrin2/ephB4

3. MSF/MCP-1

4. OPG/RANKL/RANK

5. LGR4/RANKL/RANK

6. Sema3A/Nrp

7. Osteoclast apoptosis induced by osteoblasts

8. Lysophosphatidic acid (LPA)

CLASSIFICATION OF BONES

Bones are classified in various types which are:

A. According to SHAPE 

   1. Long Bones: It has an elongated shaft known as diaphysis and two expanded ends known as epiphuses qhich are smooth and articular. Typical long bones have 3 surfaces in shaft separated by 3 borders like Humerus, Radius, Ulna, Femur, Tibia & Fibula. Miniature long bones have 1 epiphysis like Metacarpals, Metatarsals and Phalanges. Modified long bones have no medullary cavity like Clavicle.

   

   2. Short Bones: Its shape is generally cuboid, cuneiform, trapezoid or scapoid like Tarsals & Carpals.

   3. Flat Bones: It looks like shallow plates and it makes boundaries of alot of body cavities like bones of Skull, Ribs, Sternum and Scapula.

   4. Irregular Bones: It has irregular shape and structure like bones of Vertebrae, Hip and Base of Skull.

   5. Pneumatic Bones: Irregular bones containing large air spaces which make skull light in weight, resonance of voice and act as air conditioning chambers. Bones like that are Maxilla, Sphenoid, Ethmoid, etc.

   6. Sesamoid Bones: Bony nodules found embedded in tendons or joint capsules. They have no periosteum and ossify after birth, related to an articular surface, its surface of contact are covered in hyaline cartilage and lubricated by bursa or synovial membrane. Its function is to resist pressure, minimize pressure, maintains local circulation and alters direction of muscle pull. Example: Patella, Fabella, Pisiform, etc.

   7. Accessory (Supernumerary) Bones: They are not always present. They may be present as ununited epiphysis developed from extra centres of ossification. These are often bilateraland have smooth surfaceswithout any callus. Examples: Suture bones, lateral tubercle of talus (Os Trigonum), tuberosity of 5th metatarsal (Os Vesalianum), etc.

   8. Heterotropic Bones: Bones which develop in soft tissues. Rider's bone which develop in horse riders in adductor muscles.

B. According to Development

   1. Membrane (Dermal) Bones: The bones ossify in intramembrane or mesenchyme and thus derived from mesenchymal condensation. The skull and facial bones are its ideal example.

      Cartilaginous Bones: Ossification is happening in the cartilage (intracartilaginous or endochondral Ossification) like bones of limbs, vertebrate column and thorax.

      Membrano-cartilaginous: It ossifies partly in membrane and other in cartilage. Example: clavicle, mandible, occipital, temporal and sphenoid.

   2. Somatic bones: Most of the bones in human body are somatic bones.

       Visceral bones: These develop from pharyngeal arches like Hyoid bones, part of mandible and ear ossicles.

C. According to Region:

   1. Axial Skeleton 

   2. Appendicular Skeleton

D. According to Structure: 

   1. Macroscopically: It can be Compact or Cancellous:

      i. Compact Bone: It is also known as Cortical Bone. Compact bone is dense bone tissue found on the outside of a bone. Basically, in kindergarten when you drew skeletons, you were drawing compact bone. Compact bone is enclosed, except where it's covered by articular cartilage, and is covered by the periosteum. The periosteum is a thick fibrous membrane covering the entire surface of a bone and serving as an attachment for muscles and tendons. Vessels pass from the periosteum through pores into the compact bone and run through canals found throughout the tissue.

      ii. Spongy Bone (Cancellous Bone)

"Cancellous" makes it sound so negative, doesn't it? Spongy bone is on the interior of a bone and consists of slender fibers and lamellae—layers of bony tissue—that join to form a reticular structure. Spongy bone is supplied by fewer and larger vessels than compact bone. These vessels perforate the outer compact layer and are distributed into the spongy portion of bone, which is filled with marrow. Bone marrow is tissue found in long bones, like the femur, that contains stem cells.

   2. Microscopically: The bone is of 5 types, Lamellar, Woven, Fibrous, Dentine and Cement.

      i. Lamellar : Most of the human bones whether it be compact or cancellous are composed of thin plates of bony tissues also known as Lamellae. 

      ii. Woven bone : It is mainly seen in the fetal bone, fracture repair or in bone cancers.

      iii. Fibrous bone : It is found in the foetal bones.

      iv. Dentine : The teeths in humans.

      v. Cement : It occurs in the teeth.

STRUCTURE OF HUMAN BONE OF AN ADULT 

1. SHAFT: It is composed of periosteum, cortex and medullary cavity.

   a. Periosteum: It is a thick fibrous membrane covering the surface of the bone. It is made upof 2 layers, outer fibrous layer and inner cellular layer which are osteoblastic in nature. The outer fibrous layer is made up of elastic fibrous material like collagen. It consists of blood vessels and nerves which pass through dense and compact layer of bone known as bone cortex. The inner cellular layer also known as Cambium consists of Osteoblast cells. This layer thinner with age. 

   b. Cortex: This is made up of a compact bone which gives it the desired strength to withstand all possible strains.

   c. Medullary Cavity: The cavity is made up of red or yellow bone marrow. At birth the marrow is red everywhere with widespread active haemopoiesis, with advancement of age the red marrow atrophies at many places and is replaced by yellow, fatty marrow with no power of haemopoiesis. Red marrow is present in cancellous bones at the ends throughout the life.

2. TWO ENDS: The long bones are made up of cancellous bones which are covered with Hyaline cartilage.

PARTS OF THE BONE:

1. Epiphysis is ends and tips of the bone which ossify from secondary centres. it has following types:

   a. Pressure Epiphysis is articular and takes part in transmission of weight.

   b. Traction Epiphysis is nonatrticular and doesn't bear weight, it provides attachment to tendons which exert traction at the epiphysis. The traction epiphysis ossify later than the pressure epiphysis.

   c. Atavistic Epiphysis is phylogenetically an independent bone which in man becomes an independent bone.

   d. Aberrant Epiphysis isn't always present.

2. Diaphysis is an elongated shaft of the long bone which ossifies from primary centres.

3. Metaphysis are the epiphysial ends of the diaphysis. It contains growth plate which grows and ossifies near diaphysis and epiphysis. The metaphysis contains mesenchymal stem cells which gives rise to bone and fat cells, also it contains haematopoietic stem cells which gives rise to alot of blood vessels and osteoclasts. during childhood, the growth plate contains the connecting cartilage which helps in growth. The components of growth plate stop growing alltogether and completely and ossify in a complete bone. In an adult, the metaphysis functions to transfer loads of weight bearing joint surfaces to diaphysis.

DEVELOPMENT AND OSSIFICATION OF BONE

The development of the skeleton can be traced back to three derivatives[1]: cranial neural crest cells, somites, and the lateral plate mesoderm. Cranial neural crest cells form the flat bones of the skull, clavicle, and the cranial bones (excluding a portion of the temporal and occipital bones. Somites form the remainder of the axial skeleton. The lateral plate mesoderm forms the long bones

Bone formation requires a template for development. This template is mostly cartilage, derived from embryonic mesoderm, but also includes undifferentiated mesenchyme (fibrous membranes) in the case of intramembranous ossification. This framework determines where the bones will develop. By the time of birth, the majority of cartilage has undergone replacement by bone, but ossification will continue throughout growth and into the mid-twenties.   

Intramembranous Ossification

This process involves the direct conversion of mesenchyme to the bone. It begins when neural crest-derived mesenchymal cells differentiate into specialized, bone-forming cells called osteoblasts. Osteoblasts group into clusters and form an ossification center. Osteoblasts begin secreting osteoid, an unmineralized collagen-proteoglycan matrix that can bind calcium. The binding of calcium to osteoid results in the hardening of the matrix and entrapment of osteoblasts. This entrapment results in the transformation of osteoblasts to osteocytes. As osteoid continues to be secreted by osteoblasts, it surrounds blood vessels, forming trabecular/cancellous/spongy bone. These vessels will eventually form the red bone marrow. Mesenchymal cells on the surface of the bone form a membrane called the periosteum. Cells on the inner surface of the periosteum differentiate into osteoblasts and secrete osteoid parallel to that of the existing matrix, thus forming layers. These layers are collectively called the compact/cortical bone [2].

Five steps can summarize intramembranous ossification:

1. Mesenchymal cells differentiate into osteoblasts and group into ossification centers
2. Osteoblasts become entrapped by the osteoid they secrete, transforming them to osteocytes
3. Trabecular bone and periosteum form
4. Cortical bone forms superficially to the trabecular bone
5. Blood vessels form the red marrow

Endochondral Ossification

This process involves the replacement of hyaline cartilage with bone. It begins when mesoderm-derived mesenchymal cells differentiate into chondrocytes. Chondrocytes proliferate rapidly and secrete an extracellular matrix to form the cartilage model for bone. The cartilage model includes hyaline cartilage resembling the shape of the future bone as well as a surrounding membrane called the perichondrium. Chondrocytes near the center of the bony model begin to undergo hypertrophy and start adding collagen X and more fibronectin to the matrix that they produce; this altered matrix allows for calcification. The calcification of the extracellular matrix prevents nutrients from reaching the chondrocytes and causes them to undergo apoptosis. The resulting cell death creates voids in the cartilage template and allows blood vessels to invade. Blood vessels further enlarge the spaces, which eventually combine and become the medullary cavity; they also carry in osteogenic cells and trigger the transformation of perichondrium to the periosteum. Osteoblasts then create a thickened region of compact bone in the diaphyseal region of the periosteum, called the periosteal collar. It is here that the primary ossification center forms. While bone is replacing cartilage in the diaphysis, cartilage continues to proliferate at the ends of the bone, increasing bone length. These proliferative areas become the epiphyseal plates (physeal plates/growth plates), which provide longitudinal growth of bones after birth and into early adulthood. After birth, this entire process repeats itself in the epiphyseal region; this is where the secondary ossification center forms [3].

The physeal growth plate is separated into various sections based on pathologic characteristics. 

• Reserve Zone
  • Storage site for lipids, glycogen, proteoglycan 
• Proliferative Zone
  • Proliferating chondrocytes leading to longitudinal growth
• Hypertrophic Zone
  • Site of chondrocyte maturation
  • Within the hypertrophic zone, the chondrocytes go through a transformation process. The chondrocyte mature and prepare a matrix for calcification; then they degenerate which allows calcium release for calcification of the matrix. 
• Primary Spongiosa
  • Site for mineralization to form woven bone
  • Vascular invasion occurs
• Secondary Spongiosa
  • Internal modeling with the replacement of fiber bone with lamellar bone
  • External modeling with funnelization

Five steps can summarize endochondral ossification:

1. Mesenchymal cells differentiate into chondrocytes and form the cartilage model for bone
2. Chondrocytes near the center of the cartilage model undergo hypertrophy and alter the contents of the matrix they secrete, enabling mineralization
3. Chondrocytes undergo apoptosis due to decreased nutrient availability; blood vessels invade and bring osteogenic cells
4. Primary ossification center forms in the diaphyseal region of the periosteum called the periosteal collar
5. Secondary ossification centers develop in the epiphyseal region after birth

BONE'S BLOOD SUPPLY

Introduction

Bone receives 5-10% of cardiac output Bones that receive tenuous blood supply scaphoid talus femoral head odontoid Blood supply to long bone comes from three sources  nutrient artery system metaphyseal-epiphyseal system periosteal system

Nutrient Artery System

High pressure system that branches from major systemic arteries Enter the cortex through the nutrient foramen and enter the medullary canal then branch into ascending and descending branches then branch into arterioles and supply the inner 2/3 of mature bone via the haversion system

Metaphyseal epiphyseal system

Arteries arise from periarticular vascular plexus e.g. geniculate arteries

Periosteal System

Low pressure system that supplies the outer 1/3 of bone connected by Volkman's artery (perpendicular to long axis) Haversion system (parallel to long axis)

Intracortical Vascularization

Intracortical vessels travel within canals Primary Haversian canals Secondary Volkmann canals

Direction of Arterial Flow

Normal intraosseous blood flow rate is 5-20ml/min/100g of bone  Mature bone flow is centrifugal (inside to outside) because of high pressure nutrient artery system and low pressure periosteal system Immature bone flow is centripetal (outside to inside) because low pressure periosteal system predominates Factors increasing blood flow hypoxia hypercapnia sympathectomy

Direction of Venous Flow

Mature bone  flow is centripetal (outside to inside) cortical capillaries drain to venous sinusoids, which drain to the emissary venous system

Growth Plate

Perichondrial artery is the major source of nutrition of the growth plate

Pathoanatomy

Fractures patterns of blood flow following fracture immediate phase initial decrease in blood flow after fracture flow is centripetal (outside to inside) because high pressure nutrient artery system is disrupted low pressure periosteal system predominates hours to days increase in blood flow (regional acceleratory phenomenon) peaks at 2 weeks and returns to normal in 3-5 months Intramedullary nails unreamed intramedullary nails preserve endosteal blood supply reaming devascularizes inner 50-80% of the cortex and delays revascularization of endosteal blood supply loose fitting nails spare cortical perfusion and allow more rapid reperfusion tight fitting nails compromise cortical perfusion and reperfusion is slow NERVE SUPPLY OF BONE  Nerves accompny the blood vessels. Most of them are sympathetic and vasomotor in function. A few of them are sensory which are distributed to the articular ends and periosteum of the long bones, to vertebra and to the large flat bones. COMPLIED AND WRITTEN BY: Dr. Palak Shah