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What are the 2 types of bones in the body?
- 1. Endochondral
- 2. Membrane (Dermal)
- most of the bones in the body are Endochonral: long bones of the extremities, ribs, other bones of the thorax, vertebrae, & pelvis
- most of the flat bones of the skull are Membrane bones & form completely differently than the endochondral bones
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What process forms Endochondral bones?
- Endochondral Ossification
- start with a cartilage template that resembles a small version of the adult bone & use it to deposit bone on
- bone initially deposited is called Woven bone
- after remodeling it BECOMES lamellar (compact or spongy)
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Steps of Endochondral Ossification
- start with a cartilage template that somewhat resembles the adult bone that’s going to be formed
- 1. chondrocytes in the center of the cartilage (mini-bone template) begin to ENLARGE (hypertrophy); they will eventually die, & the cartilage in between them will become calcified
- that will make the region porous so blood vessels can enter, bringing with them osteogenic cells (blasts + clasts)
- 2. osteoblasts will start laying new bone on top of the calcified cartilage
- this forms the Primary Center of Ossification
- 3. at about the same time all that’s going on, the Periosteal Collar is being made; this is bone that’s forming around the shaft/diaphysis
- the collar is DE NOVO bone synthesis - new bone is made on the edge of hyaline cartilage (no template)
- perichondrium → periosteal collar → bony collar
- 4. the same events that occurred to form the Primary Center of Ossification now happen at the 2 Epiphyseal ends: hyaline cartilage chondrocytes hypertrophy, intervening cartilage calcifies, chondrocytes die, ingrowth of blood vessels + osteoprogenitor cells, new bone is laid down on top of calcified cartilage
- these are called the Secondary Centers of Ossification
- 5. a portion of hyaline cartilage called the Epiphyseal Plate is maintained between both Secondary Centers of Ossification & the central Primary Center of Ossification
- the Epiphyseal Plate is what allows long bones to grow in length

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- can see hyaline cartilage on the two ends
- however central hyaline cartilage contains much larger cells (hypertrophied)
- cartilage in between cells is going to become calcified (stains blue/purple instead of pink)
- chrondrocytes will die
- area becomes porous, allowing BVs to migrate in & bring with them osteogenic cells to build bone on the calcified cartilage
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Epiphyseal Growth Plate
 - Resting: standard hyaline cartilage (see double Ds, there’s some division)
- Proliferating: when cells proliferate in earnest they do so along the long axis, parallel to the bone - resembles a “stack of coins” as opposed to just a clump of cells
- Hypertrophic: chondrocytes are much LARGER & the in between cartilage is darker than in the resting & proliferating zones - this is because it’s undergoing CALCIFICATION
- Calcified: calcified cartilage is the template upon which osteoblasts will lay down new bone; chondrocytes are dead in this type of bone
- the calcified end is closest to the Primary Center of Ossification (diaphysis)

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What is diagnostic of Endochondral Ossification?
- osteoblasts laying down new bone on top of calcified cartilage - MIXED SPICULES
 - blue: CC (calcified cartilage) - blue because it has lots of sulfated proteoglycans, binds the eiosin
- pink: bone, more rich in cartilage so it binds the hemotoxalin
- you know this is new bone because of the osteoid being synthesized by osteoblasts
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Epiphyseal Plate Thickness
- stays the same thickness, just shifts ‘up’ toward the epiphysis
- there’s erosion of hyaline cartilage at the diaphyseal end, & addition of hyaline cartilage at the epiphyseal end
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What happens when the Epiphyseal Growth Plate closes?
- there’s no longer proliferation of chondrocytes at the ‘epiphyseal’ (upper) end, but there’s STILL erosion of them at the diaphyseal end
- eventually the plate gets thinner & thinner → eventually disappears
- in adult bone there’s no evidence of it whatsoever
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Bone Remodeling
- bones remodel throughout life as well as to repair fractures & especially during development
- the woven bone initially deposited is very disorganized - doesn’t have the strength of lamellar bone
- both spongy & compact bone need to be remodeled after initial placement
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What bone initially makes up the bone collar?
- the bone collar is initially formed as SPONGY bone - have lots of marrow spaces
- these will eventually be filled in by osteoblasts until what’s left is compact (Haversian) bone
- but Haversian systems don’t come about UNTIL remodeling
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Compact Bone Remodeling
- osteoclasts excavate a channel
- once there’s exposed bone, osteoblasts are recruited to the wall of the channel, line up & begin synthesizing bone
- some will get entrapped → osteocyte, while the rest continue to form the Osteon
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- image shows Osteons (Haversian systems) in development
- faint blue/purple line shows the extent to which osteoclasts excavated the bone (initial channel that was created)
- osteoblasts lined up on that surface & laid down new bone
- some osteoblasts became trapped → osteocyte
- the rest can be seen synthesizing new bone (Osteoid)

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Spongy Bone Remodeling
- during development, the spicules are small & not robust
- they need to enlarge & become thicker to form adult bone
 - there will be removal of woven bone by osteoclasts, & new lamellar bone will get deposited by osteoblasts
- space for red bone marrow still exists even in adult spongy bone
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Intramembranous Ossification
- builds the flat bones in the cranium & face
- bone formation will begin DE NOVO, from condensation of mesenchyme
- there’s NO cartilage template
- bone will be initially deposited woven, then remodeled into compact & spongy bone as needed
- have important difference in terms of bone building, but once Intramembranous bone is BUILT, it’s remodeled in the exact same way as Endochondral bone

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- see condensation of mesenchyme & cells differentiating into osteoblasts
- bone is initially made as woven spongy bone
- if the bone is supposed to become compact, the white spaces will be filled in, followed by remodeling to Haversian systems
- if the bone is supposed to stay spongey, then the marrow spaces would persist
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periosteal vs. endosteal lamellae
periosteal (outer) lamellae lie beneath the periosteum while endosteal (inner) lamellae lie beneath the endosteum
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endosteum
- a thin layer of connective tissue that lines the medullary cavity
- endosteum have osteogenic capability (stem cells are available on all surfaces of bone tissue)
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periosteum
- a tough dense connective tissue that surrounds the outer surface of bone organs EXCEPT at articular surfaces
- it's anchored to the underlying bone tissue by bundles of collagen fibers (Sharpey fibers) which penetrate perpendicularly into the bone
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intramembranous ossification (bone formation)
- when primitive mesenchymal cells differentiate immediately into bone
- early on, mesenchymal cells differentiate into osteoblasts and lay down bone matrix
- as it is initially laid down, the bone is spongy & woven
- mesenchyme --> bone
- how flat bones of skull/jaw form
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endochondral ossification (bone formation)
- when primitive mesenchymal cells differentiate first into chrondrocytes of hyaline cartilage
- they enlarge then die and leave behind cartilage matrix that becomes calcified (calcified MATRIX)
- this calcified matrix induces other mesenchymal cells to differentiate into osteoblasts
- these secrete bone matrix over the surface of calcified cartilage spicules
- mesenchyme --> hyaline cartilage --> bone
- how the long bones form
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How can one differentiate endochondral bone from intramembranous bone?
endochondral bone spicules have a calcified basophilic cartilage matrix core (it's the hallmark of newly made endocondral bone)
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Are these statements about osteogenesis true or false?
- 1) all compact bone tissue forms first as spongy bone
- 2) all bone tissue forms first as osteoid
- 3) all bone tissue grows by apposition only
- They're all TRUE
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