Notes on Osteogenesis

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Definition of Osteogenesis:

Osteogenesis is the process of bone formation.

Two Types of Osteogenesis:

Intramembranous or direct bone formation:

• Occurs when mesenchyme is directly transformed to bone.

Endochondral bone formation:

• Occurs when a cartilage model of a bone is produced that is then replaced by bone.

Where does intramembranous endochondral ossification occur?

• Skull vault.

• Manbibles.

• Flat bones of the face.

• Clavicle.

• Terminal phalanges.

• Periosteal bone collar of long bones.

Formation of Osteoblasts:

Vascularized mesenchyme in flat bones, etc. differentiates into osteoblasts.

Function of Osteoblasts:

Osteoblasts produce osteoid which undergoes transformation into bone. Bone initially occurs as short bony islands or spicules. Spicules are increased in size to trabeculae by rows of osteoblasts at their surface. Trabeculae interact to form spongy bone separated by hemopoietic tissue.

Appositional growth:

Appositional growth of trabeculae and subsequent trapping of vessels converts spongy bone to compact at the inner and outer tables of flat bones like the parietal. Outer and inner tables are compact and the intervening diploe is spongy.

Cranial Vault:

Bones of the cranial vault are separated by sutures containing blood vessels, CT and osteogenic cells, everything required for appositional growth.

Growth of the Cranial Vault:

• Peripheral bone growth at sutures.

• Bone deposition on convex surface.

• Bone resorption on concave surface to avoid undue thickness.

Endochondral Bone Formation:

Endochondral bone formation establishes a hyaline cartilage model and subsequently replaces it with bone. Occurs in most all major long bones.

Steps in Endochondral bone formation:

Mesenchyme condenses into the shape of the developing bone.

Mesenchyme differentiates into chondroblasts and forms a hyaline cartilage model of the future bone. Chondroblasts produce hyaline cartilage matrix. Perichondrium develops around the model at mid-shaft. Model grows by: appositional growth from perichondrium adds to the width interstitial growth at ends lengthens the model.

Chondrocytes in the middle of the model hypertrophy, become calcified and these chondrocytes die. Capillaries grow toward perichondrium and the oxygenated environment converts it to a periosteum Osteoblasts produce a bony collar via the intramembranous method around the model at mid-shaft Presence of the bony collar and periosteum prevent nutrients from reaching the middle of the model and chondrocytes die and leave empty lacunae surrounded by calcified cartilage matrix.

Osteoclasts pierce the bony collar and a periosteal bud consisting of a vessel and osteogenic cells pierce the cartilage model establishing the primary center of ossification Osteogenic cells become osteoblasts and lay down osteoid on remnants of calcified cartilage matrix Osteoclasts resorb the calcified cartilage matrix and the center of the spongy bone to create the marrow cavity which becomes seeded by circulating hemopoietic cells to produce marrow.

The central portion of the model is now bone but the two ends remain hyaline cartilage At about birth, blood vessels grow into the calcified cartilage of the epiphyses to form secondary centers of ossification. There is no bony collar. A radial wave of ossification follows. The epiphyseal plates stay the same size because they are added to by interstitial growth of cartilage on the epiphyseal side and are converted to bone on the diaphyseal side. Bone replacement catches up with cartilage production and the epiphyseal plates disappear when the bone is of the adult size.

Zones of Epiphyseal Plates:

Resting, proliferating, maturing, and calcification ossification.

Resting Ossification:

Normal resting hyaline cartilage.

Proliferative Ossification:

Proliferative - cells divide to replace ones lost to bone on the diaphyseal side Maturation - cells enlarge, accumulate glycogen and lipid and produce alkaline phosphatase which facilitates calcification of the matrix

Calcification Ossification:

Calcification Ossification - capillaries with osteogenic cells from the marrow cavity invade. Osteoclats remove calcified matrix and some bone while osteblasts lay down osteoid and eventually bone.

Structural Bone:

• Heavily mineralized weight bearing bone consisting of old mature osteons and interstitial lamellae.

Metabolic Bone:

• Immature bone that is still laying down minerals.

• Osteoclast activity constantly contributes to bone remodeling.

• Osteoclasts release lysosomal enzymes that degrade collagen, GAGs of bone matrix.

• Carbonic, lactic and citric acids from osteoclasts dissolve hydroxyapatite releasing calcium and phosphate ions.

Role of Parathyroid Glands in Bone Formation:

Parathyroid glands produce parathormone which increases activity of osteoclasts that leads to a release of calcium ions to the blood. Parathormone also:

• Increases blood calcium by reducing loss by the kidney.

• Increases absorption of calcium by the small intestine, hence, the parathyroid gland maintains a constant level of calcium in the blood.

Thyroid C cells produce calcitonin which inhibits osteoclast activity and therefore antagonizes parathormone.


Scurvy occurs due to deficiency of vitamin C, results in impaired collagen formation, hence a decrease in the formation of bone matrix.


Rickets occurs due to deficiency of vitamin D in children. Results in inability to absorb calcium from the gut and lack of cartilage mineralization. Children have bow legs because bones cannot bear the weight.

Vitamin A Deficiency:

Vitamin A - deficiency leads to a slowing of growth, early closing of the epiphyseal plate, hence dwarfism.

Function of Growth Hormine:

Growth hormone, produced by the anterior pituitary, stimulates growth of epiphyseal plates. Children deficient in GH are pituitary dwarfs. Children with excess are pituitary giants.


Acromegaly is characterized by excess GH in adults. An abnormal increase in bone deposition without normal resorption. Thickening of facial bones and soft tissue disfiguring also occur.


Osteoporosis is characterized by loss in total bone mass. Seen in elderly, disuse (astronauts), women over 40 and many postmenopausal women not on estrogen therapy. Estrogen production drops at menopause. Normally estrogen stimulates osteoblasts but with decreased estrogen osteoclasts are relatively more active. Estrogen therapy may reduce or eliminate this condition.

Additional Reading:

Basic Histology

1. Introduction to Histology
2. Basic Cell Physiology
3. Actin, Microtubules, and Intermediate Filaments
4. Mitochondria, Nucleus, Endoplasmic Reticulum, Golgi
5. Epithelium (Epithelial Tissue)
6. Connective and Adipose Tissue
7. Types of Cartilage
8. Osteogenesis
9. Nervous Tissue
10. Muscle Tissue
11. Cardiovascular System
12. Blood and Hematopoiesis
13. Lymphoid Tissue
14. Digestive Tract I: Oral Cavity
15. Digestive Tract II: Esophagus through Intestines
16. Liver, Pancreas, and Gall Bladder
17. Respiratory System
18. Integument
19. Urinary System
20. Endocrine System
21. Male Reproductive System
22. Female Reproductive System
23. Eye and Ear

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