La osificación es el proceso y el resultado de osificar, un verbo que refiere al proceso que lleva a un elemento orgánico a transformarse en un hueso o a obtener una apariencia similar a él. A través de la osificación, por lo tanto, puede crearse un nuevo componente óseo.

1. Bones: Development and Ossification
The process of bone formation is called ossification. The 2 types of ossification are
intramembranous ossification, in which bone is developed directly from mesenchyme cells,
and endochondral ossification, in which a hyaline cartilage model is created 1st and then
later replaced with bone. Bone continues to grow into early adulthood at the epiphyseal
plates, where chondrocytes continue to divide, die, and be replaced with mineralized bone.
Bone mineralization occurs because the osteoblasts allow high levels of calcium and
phosphate to accumulate above critical threshold levels within bone.
Last updated: September 1, 2022
Overview of Bone Development
Definitions
The formation of bone is called ossification or osteogenesis.
CONTENTS
Overview of Bone Development
Endochondral Ossification
Intramembranous Ossification
Bone Growth and Mineralization
Clinical Relevance
References
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2. Types of ossification
The 2 primary types of ossification are:
Endochondral ossification: a hyaline cartilage model is created from mesenchyme, then
replaced with bone
Intramembranous ossification: bones develop directly from mesenchyme
Review of bone structure
The 2 primary types of bone are compact bone and spongy bone.
Compact bone:
Hard, dense outer layer of bones
Arranged in functional units known as osteons: a central canal containing nerves
and vessels surrounded by concentric rings of calcified bone matrix and
osteocytes
Spongy bone:
Inner layer consisting of a lattice of thin pieces of osseous tissue called
trabeculae
Found at the ends of long bones and in the middle of flat, short, and
irregular bones
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4. Endochondral Ossification
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5. Overview of endochondral ossification
Bones formed via endochondral ossification: all bones below the skull except for the
clavicles
Hyaline cartilage is used as a template for bone formation.
Process overview:
Chondrocytes create a hyaline cartilage model of the bone.
Chondrocytes within the model mature and hypertrophy → allows mineralization
Mineralization → ↓ chondrocyte nutrition → chondrocye death
Chondrocyte death creates space within the bone called lacunae.
Lacunae are invaded by vessels carrying osteoblasts, which lay down new bone.
New bone is remodeled into mature bone.
Detailed process of endochondral ossification
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6. Mesenchyme differentiates into chondroblasts.
Chondroblasts secrete a hyaline cartilage matrix:
Forms a model of the bone
Model surrounded by membrane called perichondrium
Chondroblasts trapped within the matrix become chondrocytes.
Formation of the primary ossification center:
Occurs in the diaphysis (shaft) of long bones
Chondrocytes near the center of the model mature and hypertrophy.
Hypertrophied chondrocytes alter matrix contents (add collagen X and fibronectin
) → allows mineralization to begin
Matrix mineralization:
Leads to ↓ nutrient delivery to chondrocytes → chondrocyte apoptosis
Holes (called lacunae) develop in the matrix where chondrocytes used to exist
Invasion of blood vessels:
Vascular buds (called periosteal buds) arise from the perichondrium
Grow toward the lacunae in the primary ossification center (center of diaphysis)
Carry osteogenic cells with them into the lacunae:
Osteoblasts form new bone.
Osteoclasts break down bone and matrix.
Invading periosteal buds break down walls between lacunae, creating the primary
marrow space (which will eventually become the medullary cavity).
Seeding of osteogenic cells:
Periosteal buds deposit osteoblasts into the marrow space.
At the same time, perichondrium ossifies into a bony collar surrounding the
forming bone → now known as periosteum
Osteoblasts create woven bone:
Osteoblasts now lining the marrow spaces lay down osteoid tissue (organic
components of bone matrix) and calcify it → called woven bone
Bone remodeling (via osteoclasts and osteoblasts) replaces woven bone with
mature trabecular (spongy) bone
Growth in bone length:
Cartilage continues dividing at the epiphyses → ↑ bone length
Area is known as the epiphyseal plates (i.e., growth plates).
Continues providing longitudinal growth into early adulthood
Secondary ossification centers:
Located within the epiphyses
Appear around the time of birth
Follow the same pattern as the primary ossification center:
Matrix mineralization
Chondrocyte death → creation of lacunae
Invasion of blood vessels
Seeding of the lacunae with osteoblasts, which create bone
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7. After birth, cartilage remains at:
Articular surfaces
Epiphyseal plates:
Also known as growth plates
Ossify after puberty (resulting in no further longitudinal growth)
Process of endochondral ossification
Image: “Process of endochondral ossification” by CNX OpenStax. License: CC BY 4.0
Intramembranous Ossification
Intramembranous ossification is a direct conversion of mesenchymal cells into
osseous tissue.
Bones formed via intramembranous ossification
These bones have a middle layer of spongy bone sandwiched between layers of
compact bone:
Flat bones of the skull
Facial bones
Mandible
Clavicle
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8. Structure of a flat bone
Image: “This cross-section of a flat bone shows the spongy bone (diploë) lined on either side by a layer of compact
bone” by OpenStax College. License: CC BY 4.0
Process
Mesenchymal cells condense into sheets and differentiate into:
Osteogenic cells → further differentiate into osteoblasts
Capillaries
Between mesenchymal sheets:
Osteogenic cells/osteoblasts condense into ossification centers
Osteoblasts begin secreting osteoid: soft collagenous bone matrix (soft
trabeculae)
Trabeculae grow → osteoblasts deposit calcium phosphate onto the matrix
Osteoblasts trapped within the mineralizing matrix transform into osteocytes
Mineralized trabeculae:
Middle portion: becomes permanent spongy bone (middle layer of flat bones)
Surface portions:
Continue calcifying until all the spaces are filled in → compact bone
Remodeling occurs via osteoclasts and osteoblasts to form lamellar bone.
Surface mesenchyme:
Remains uncalcified
Becomes more and more fibrous
Eventually differentiates into periosteum
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9. Process of intramembranous ossification
Image: “Intramembranous ossification follows four steps. (a) Mesenchymal cells group into clusters, and ossification
centers form. (b) Secreted osteoid traps osteoblasts, which then become osteocytes. (c) Trabecular matrix and
periosteum form. (d) Compact bone develops superficial to the trabecular bone, and crowded blood vessels condense
into red marrow.” by OpenStax College. License: CC BY 4.0
Bone Growth and Mineralization
Bone growth
The epiphyseal plates are found in the metaphysis of long bones, the transitional region
between the diaphysis (shaft) and epiphysis (ends). There are 5 distinct histologic
zones:
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10. 1. Zone of reserve cartilage:
Located farthest from the marrow
Consists of resting cartilage
The chondrocytes disappear after puberty → “closing” the growth plates
2. Zone of proliferation:
Chondrocytes arrange themselves in columns and divide.
Leads to longitudinal growth
3. Zone of hypertrophy:
Chondrocytes hypertrophy, mature, and transform (just as in
endochondral ossification).
Allows for mineralization and additional longitudinal growth
4. Zone of calcification: Matrix is mineralized.
5. Zone of resorption and bone deposition:
Chondrocytes die, creating longitudinal channels that are invaded by vessels
carrying osteogenic cells.
Osteoclasts dissolve the calcified cartilage.
Osteoblasts line the channel walls and lay down concentric lamellae of matrix
until only a narrow channel remains → the central channel of a mature osteon
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11. Histologic zones of the epiphyseal plates
Image by Lecturio.
Bone mineralization
Calcium (Ca2+) and phosphate (PO4
3–) combine to form hydroxyapatite crystals on the
bone matrix.
Crystals can form only when certain threshold levels for Ca2+ and PO4
3– are exceeded:
Most tissues have inhibitors preventing this from happening.
Bone-forming cells secrete osteocalcin, which binds extracellular Ca2+ → allows
Ca2+ to accumulate
Osteoblasts respond to ↑ Ca2+ by secreting alkaline phosphatase, which ↑ PO4
3– ions.
At ↑ levels, calcium and phosphate crystallize into hydroxyapatite crystals (Ca
10(PO4)6OH2) on the organic matrix.
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12. Clinical Relevance
Achondroplasia: autosomal dominant condition caused by mutations in the FGFR3
gene, which inhibits chondrocyte proliferation, impairing endochondral bone formation.
Clinically, achondroplasia presents in infants with short stature, shortening of the limbs,
characteristic facies, abnormalities in the spinal curvature, and slow motor
development. Intellectual development is normal. Management is aimed at optimizing
functional capacity and treating complications, such as recurrent ear infections, sleep
apnea, leg bowing, and spinal stenosis.
Osteogenesis imperfecta: also known as “brittle bone disease.”
Osteogenesis imperfecta is a rare genetic connective tissue disorder characterized by
severe bone fragility. Although it is considered a single disease, it includes over 16
genotypes, with the most common types causing mutations in type 1 collagen. Some
forms are lethal in utero. There is no definitive cure; treatment is supportive, usually
involving bisphosphonates, and is focused on reducing pain, fracture frequency, and
bone deformity and increasing ambulation.
Rickets: disorder of decreased bone mineralization in children. In rickets, the
hypertrophic chondrocytes in the epiphyseal growth plates fail to undergo apoptosis.
This failure results in insufficient mineralization of the cartilage and is most commonly
due to a deficiency in vitamin D, the vitamin that promotes bone mineralization. Rickets
presents with skeletal deformities, including bowed legs, and growth abnormalities.
Treatment includes vitamin D, calcium, and phosphorus supplementation.
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13. Rickets
Image: “X-rays of both lower limbs showing severe bowing of the legs and diffuse osteopenia. It also shows dense
transverse lines in the tibia suggestive of looser’s zones indicative of rickets” by Al-Sharafi BA et al. License: CC BY 4.0
References
1. Saladin, K.S., Miller, L. (2004). Anatomy and physiology, 3rd ed. pp. 218–224. McGraw Hill Education.
2. Manolagas, S.C. (2020). Normal skeletal development and regulation of bone formation and resorption.
UpToDate. Retrieved August 4, 2021, from https://www.uptodate.com/contents/normal-skeletal-
development-and-regulation-of-bone-formation-and-resorption
3. Breeland, G. (2021). Embryology, bone ossification. StatPearls. Retrieved August 6, 2021, from
https://www.statpearls.com/articlelibrary/viewarticle/36128/
4. OpenStax College, Anatomy and Physiology. OpenStax CNX. Retrieved August 5, 2021, from
https://philschatz.com/anatomy-book/contents/m46301.html
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