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Ossification (also called osteogenesis or bone mineralization) in is the process of laying down new material by cells named . It is synonymous with formation. There are two processes resulting in the formation of normal, : Intramembranous ossification is the direct laying down of bone into the primitive connective tissue (), while endochondral ossification involves as a precursor.

In , endochondral is the most commonly occurring process, for example in fractures of long treated by plaster of Paris, whereas fractures treated by open reduction and internal fixation with plates, , pins, rods and nails may heal by intramembranous .

Heterotopic ossification is a process resulting in the formation of that is often atypical, at an extraskeletal location. is often confused with ossification. Calcification is synonymous with the formation of -based salts and crystals within cells and tissue. It is a process that occurs during ossification, but not necessarily vice versa.

The exact mechanisms by which development is triggered remains unclear, but and appear to play a role.

Third month of fetal developmentOssification in long bones beginning
Fourth monthMost primary ossification centers have appeared in the diaphyses of bone.
Birth to five yearsSecondary ossification centers appear in the epiphyses
five years to 12 years in females, 5 to 14 years in malesOssification is spreading rapidly from the ossification centers and various bones are becoming ossified.

17 to 20 yearsBone of upper limbs and becoming completely ossified
18 to 23 yearsBone of the lower limbs and become completely ossified
23 to 26 yearsBone of the , , and become completely ossified
By 25 yearsNearly all bones are completely ossified


Intramembranous ossification
Intramembranous ossification forms the of the , and .

Osteoblasts cluster together to create an ossification center. They then start secreting osteoid, an unmineralized collagen-proteoglycan matrix that has the ability to bind calcium. As calcium binds to the osteoid, the matrix hardens, and the osteoblasts become entrapped, transforming into osteocytes.

As osteoblasts continue to secrete , it surrounds blood vessels, leading to the formation of trabecular (cancellous or spongy) bone. These blood vessels will eventually develop into red bone marrow. Mesenchymal cells on the bone surface form a membrane known as the periosteum. Osteoblasts secrete osteoid in parallel with the existing matrix, creating layers of compact (cortical) bone.


Endochondral ossification
Endochondral ossification is the formation of long bones and other bones. This requires a hyaline cartilage precursor. There are two centers of ossification for endochondral ossification.

The primary center

In long bones, bone tissue first appears in the (middle of shaft). multiply and form trebeculae. Cartilage is progressively eroded and replaced by hardened bone, extending towards the . A layer surrounding the cartilage forms the , which generates osteogenic cells that then go on to make a collar that encircles the outside of the bone and remodels the medullary cavity on the inside.

The nutrient artery enters via the from a small opening in the diaphysis. It invades the primary center of ossification, bringing osteogenic cells ( on the outside, on the inside.) The canal of the is directed away from more active end of bone when one end grows more than the other. When bone grows at same rate at both ends, the nutrient artery is perpendicular to the bone.

Most other bones (e.g. ) also have primary ossification centers, and bone is laid down in a similar manner.

Secondary centers

The secondary centers generally appear at the . Secondary ossification mostly occurs after birth (except for distal femur and proximal which occurs during 9th month of fetal development). The epiphyseal arteries and osteogenic cells invade the , depositing and which erode the cartilage and build bone, respectively. This occurs at both ends of long bones but only one end of digits and ribs.


Evolution
Several hypotheses have been proposed for how bone evolved as a structural element in . One hypothesis is that bone developed from tissues that evolved to store . Specifically, calcium-based minerals were stored in cartilage and bone was an development from this calcified cartilage. However, other possibilities include bony tissue evolving as an , or as a protective structure.


See also
  • Dystrophic calcification
  • , a model describing ossification and bone loss
  • , the horn-like (or antler-like) protuberances on the heads of giraffes and related species
  • Osteogenesis imperfecta, a juvenile bone disease
  • Fibrodysplasia ossificans progressiva, an extremely rare genetic disease which causes fibrous tissue (muscle, tendon, ligament etc.) to ossify when damaged
  • Primrose syndrome, a rare genetic disease in which cartilage becomes ossified.

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