Ossification

This article is about the biological process. For the concept in computer networking, seeProtocol ossification.

Bone is broken down by osteoclasts, and rebuilt by osteoblasts, both of which communicate through cytokine (TGF-β,IGF) signalling.

Ossification(also calledosteogenesisorbone mineralization) inbone remodelingis the process of laying down newbonematerial bycellsnamedosteoblasts.It is synonymous withbone tissueformation.There are two processes resulting in the formation of normal,healthybone tissue:Intramembranous ossificationis the direct laying down of bone into the primitive connective tissue (mesenchyme), whileendochondral ossificationinvolvescartilageas a precursor.

Infracture healing,endochondralosteogenesisis the most commonly occurring process, for example in fractures of longbonestreated byplaster of Paris,whereas fractures treated byopen reduction and internal fixationwithmetalplates,screws,pins, rods and nails may heal by intramembranousosteogenesis.

Heterotopic ossificationis a process resulting in the formation ofbone tissuethat is often atypical, at an extraskeletal location.Calcificationis often confused with ossification.Calcificationis synonymous with the formation ofcalcium-based salts and crystals withincellsandtissue.It is a process that occurs during ossification, but not necessarilyvice versa.

The exact mechanisms by whichbonedevelopment is triggered remains unclear, butgrowth factorsandcytokinesappear to play a role.

Time period	Bones affected
Third month of fetal development	Ossification in long bones beginning
Fourth month	Most primaryossification centershave appeared in the diaphyses of bone.
Birth to 5 years	Secondary ossification centers appear in the epiphyses
5 years to 12 years in females, 5 to 14 years in males	Ossification is spreading rapidly from the ossification centers and various bones are becoming ossified.
17 to 20 years	Bone of upper limbs andscapulaebecoming completely ossified
18 to 23 years	Bone of the lower limbs andos coxaebecome completely ossified
23 to 26 years	Bone of thesternum,clavicles,andvertebraebecome completely ossified
By 25 years	Nearly all bones are completely ossified

Intramembranous ossification

Intramembranous ossificationforms theflat bonesof theskull,mandibleandhip bone.

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 secreteosteoid,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

Diagram showing stages of endochondral ossification

Endochondral ossificationis the formation of long bones and other bones. This requires ahyaline cartilageprecursor. There are two centers of ossification forendochondral ossification.

The primary center

In long bones, bone tissue first appears in thediaphysis(middle of shaft).Chondrocytesmultiply and form trebeculae. Cartilage is progressively eroded and replaced by hardened bone, extending towards theepiphysis.Aperichondriumlayer surrounding the cartilage forms theperiosteum,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 thenutrient foramenfrom a small opening in the diaphysis. It invades the primary center of ossification, bringing osteogenic cells (osteoblastson the outside,osteoclastson the inside.) The canal of thenutrient foramenis 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.vertebrae) also have primary ossification centers, and bone is laid down in a similar manner.

Secondary centers

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

Microscopic image of thegrowth plate

Evolution

Aspotted garlarva at 22 days stained forcartilage(blue) and bone (red).

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

See also

• Dystrophic calcification
• Mechanostat,a model describing ossification and bone loss
• Ossicone,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.