Editing Ossification

{{Short description|Development process in bones}}
{{About|the biological process|the concept in computer networking|Protocol ossification}}
{{multiple issues|{{more citations needed|date=May 2011}}
{{update|{{PMID|24292720}}|date=October 2017}}
}}

[[Image:Bonemetabolism.svg|thumb|300 px|right|Bone is broken down by osteoclasts, and rebuilt by osteoblasts, both of which communicate through cytokine ([[TGF-β]], [[Insulin-like growth factor|IGF]]) signalling.]]
'''Ossification''' (also called '''osteogenesis''' or '''bone mineralization''') in [[bone remodeling]] is the process of laying down new [[bone]] material by [[Cell (biology)|cells]] named [[osteoblast]]s. It is synonymous with [[bone tissue]] formation.<ref>{{Cite web|title=bone formation {{!}} Definition & Physiology|url=https://www.britannica.com/science/bone-formation|access-date=2021-01-22|website=Encyclopedia Britannica|language=en}}</ref> There are two processes resulting in the formation of normal, [[healthy]] [[bone tissue]]:<ref>{{cite journal |vauthors=Caetano-Lopes J, Canhão H, Fonseca JE |title=Osteoblasts and bone formation |journal=Acta reumatológica portuguesa |volume=32 |issue=2 |pages=103–10 |year=2007 |pmid=17572649}}</ref> [[Intramembranous ossification]] is the direct laying down of bone into the primitive connective tissue ([[mesenchyme]]), while [[endochondral ossification]] involves [[cartilage]] as a precursor. 

In [[fracture healing]], endochondral [[osteogenesis]] is the most commonly occurring process, for example in fractures of long [[bone]]s treated by [[plaster of Paris]], whereas fractures treated by [[open reduction and internal fixation]] with [[metal]] plates, [[screws]], pins, rods and nails may heal by intramembranous [[osteogenesis]].

[[Heterotopic ossification]] is a process resulting in the formation of [[bone tissue]] that is often atypical, at an extraskeletal location. [[Calcification]] is often confused with ossification. Calcification is synonymous with the formation of [[calcium]]-based salts and crystals within [[Cell (biology)|cells]] and [[Tissue (biology)|tissue]]. It is a process that occurs during ossification, but not necessarily ''vice versa''.

The exact mechanisms by which [[bone]] development is triggered remains unclear, but [[growth factor]]s and [[cytokines]] appear to play a role.

{| class="wikitable"
|-
! Time period<ref name=Morey-Holton>{{cite web |url=http://www.nsbri.org/HumanPhysSpace/focus6/student1.html |title=Predicting Height from the Length of Limb Bones |series=Examining Effects of Space Flight on the Skeletal System |author=Emily Morey-Holton |publisher=NASA Ames Research Center |location=Moffett Field, California |archive-url=https://web.archive.org/web/20120301011824/http://www.nsbri.org/HumanPhysSpace/focus6/student1.html |archive-date=2012-03-01}}</ref>
! Bones affected<ref name=Morey-Holton/>
|-
| Third month of fetal development
| Ossification in long bones beginning
|-
| Fourth month
| Most primary [[ossification center]]s have appeared in the diaphyses of bone.
|-
| Birth to five years
| Secondary ossification centers appear in the epiphyses
|-
| five 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 and [[scapulae]] becoming completely ossified
|-
| 18 to 23 years
| Bone of the lower limbs and [[os coxae]] become completely ossified
|-
| 23 to 26 years
| Bone of the [[Human sternum|sternum]], [[clavicle]]s, and [[vertebrae]] become completely ossified
|-
| By 25 years
| Nearly all bones are completely ossified
|}

==Intramembranous ossification==
{{Expand section|date=January 2021}}
[[Intramembranous ossification]] forms the [[flat bone]]s of the [[skull]], [[mandible]] and [[hip 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 secrete [[osteoid]], 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.<ref>{{Citation |last=Breeland |first=Grant |title=Embryology, Bone Ossification |date=2024 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK539718/ |access-date=2024-05-15 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30969540 |last2=Sinkler |first2=Margaret A. |last3=Menezes |first3=Ritesh G.}}</ref>

==Endochondral ossification==
[[File:Bone growth -- Smart-Servier (cropped).jpg|thumb|Diagram showing stages of 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 [[diaphysis]] (middle of shaft). [[Chondrocyte]]s multiply and form trebeculae. Cartilage is progressively eroded and replaced by hardened bone, extending towards the [[epiphysis]]. A [[perichondrium]] layer surrounding the cartilage forms the [[periosteum]], 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 [[Nutrient canal|nutrient foramen]] from a small opening in the diaphysis. It invades the primary center of ossification, bringing osteogenic cells ([[osteoblast]]s on the outside, [[osteoclast]]s on the inside.) The canal of the [[Nutrient canal|nutrient foramen]] 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. [[vertebra]]e) also have primary ossification centers, and bone is laid down in a similar manner.

'''Secondary centers'''

The secondary centers generally appear at the [[epiphysis]]. Secondary ossification mostly occurs after birth (except for distal femur and proximal [[tibia]] which occurs during 9th month of fetal development). The epiphyseal arteries and osteogenic cells invade the [[epiphysis]], depositing [[osteoclast]]s and [[osteoblast]]s which erode the cartilage and build bone, respectively. This occurs at both ends of long bones but only one end of digits and ribs.
[[File:Proximal tibia Masson Goldner Trikrom rabbit 600x growth zone.jpg|thumb|Microscopic image of the [[epiphyseal plate|growth plate]]]]

==Evolution==
[[File:Lepisosteus oculatus larva at 22 days.png|thumb|A ''[[Lepisosteus oculatus|spotted gar]]'' larva at 22 days stained for [[cartilage]] (blue) and bone (red).]]
Several hypotheses have been proposed for how bone evolved as a structural element in [[vertebrates]]. One hypothesis is that bone developed from tissues that evolved to store [[mineral]]s. Specifically, calcium-based minerals were stored in cartilage and bone was an [[exaptation]] development from this calcified cartilage.<ref>{{cite journal |vauthors=Donoghue PC, Sansom IJ |title=Origin and early evolution of vertebrate skeletonization |journal=Microsc. Res. Tech.|issue=5 |pages=352–72 |year=2002 |pmid=12430166 |doi=10.1002/jemt.10217 |volume=59|s2cid=10933086 |doi-access=free }}</ref> However, other possibilities include bony tissue evolving as an [[Osmotic|osmotic barrier]], or as a protective structure.

==See also==
{{wiktionary}}
* [[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.

==References==
{{Commons category|Ossification}}
{{Reflist}}

{{Bone and cartilage}}
{{Bone/cartilage physiology}}
{{Ossification}}
{{Authority control}}

[[Category:Animal physiology]]
[[Category:Skeletal system]]
[[Category:Tissues (biology)|*Ossification]]