How does the perichondral bone collar form?

Intramembranously by periosteal osteoblasts

By transformation of hypertrophic cartilage

From the secondary ossification centre

What characterises the hypertrophic zone?

Large vesicular chondrocytes and calcifying matrix

Multinucleated osteoclasts in the marrow cavity

No. 28 Cartilage & bone

Endochondral ossification

Fetal phalanx · trichrome

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Fetal finger, trichrome, overview with cartilaginous phalanges, joint cleft and ossification centre — Overview Fetal finger at low power: two cartilaginous skeletal elements separated by a joint cleft; ossification has already begun in the middle of the diaphysis. Micrograph: © AnatomyProf

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In endochondral (indirect) ossification a model of hyaline cartilage is laid down first and then gradually replaced by bone. Almost all bones of the axial and limb skeleton develop this way. The fetal phalanx shows all zones within a small area – from the resting cartilage of the epiphysis to the primary marrow cavity of the diaphysis.

How to recognise it

Cartilage model with transition from resting cartilage to bone
Columnar cartilage: cells in longitudinal rows
Hypertrophic cartilage: large, vesicular chondrocytes with calcified septa
Zone of erosion with capillaries, red blood cells and mesenchyme
Perichondral bone collar beneath the periosteum
Primary trabeculae with a cartilage core

Structures to find

Epiphysis (cartilaginous) and diaphysis
Reserve zone (hyaline cartilage)
Columnar cartilage
Hypertrophic (vesicular) cartilage
Zone of erosion
Primary marrow cavity
Perichondral bone collar
Periosteum and perichondrium

Process

First the perichondral bone collar forms around the middle of the diaphysis: the perichondrium becomes periosteum, whose osteoblasts lay down a bony sleeve around the cartilage by direct ossification. The enclosed cartilage hypertrophies and calcifies. Vessels with mesenchyme and osteoclasts (chondroclasts) then invade, resorb the cartilage and open the primary marrow cavity (primary ossification centre).

Osteoblasts deposit bone on the remaining calcified cartilage septa, forming primary trabeculae with a cartilage core. Ossification advances towards both epiphyses; later, secondary ossification centres appear there, and the epiphyseal plate remains between them as the growth zone.

Zones of the growth plate

Reserve zone (resting hyaline cartilage): small, irregularly scattered chondrocytes.
Proliferative zone (columnar cartilage): flattened cells that divide and stack into longitudinal columns.
Hypertrophic zone (vesicular cartilage): greatly enlarged, bubble-like chondrocytes; the matrix between the columns calcifies.
Zone of erosion (opening zone): capillaries and chondroclasts open the cartilage lacunae from the diaphyseal side; the chondrocytes die.
Zone of ossification: osteoblasts deposit bone on the calcified longitudinal septa.

Microscopy tips

In the trichrome stain used here, cartilage matrix appears pale turquoise, bone and calcified septa dark green to reddish-brown, and red blood cells bright red. Start at the cartilaginous epiphysis at low power and follow the long axis towards the diaphysis: cells first flatten and line up in columns, then become large and vesicular, until the lacunae are finally open and contain blood and mesenchyme. Laterally you will find the dark bone collar beneath the periosteum – it extends further towards the epiphysis than the endochondral ossification front.

Clinical relevance

In achondroplasia (activating mutation of the FGFR3 gene) proliferation in the columnar zone is inhibited – long bones remain short while the intramembranously formed skull grows normally. In rickets (vitamin D deficiency) the hypertrophic cartilage fails to calcify properly, the erosion zone is irregular and the growth plates widen. Fractures through the growth plate in children (Salter–Harris classification) can lead to growth disturbances.

Slide images

Fetal finger, trichrome, overview with ossifying skeletal element, marrow space and skin — **Overview:** Section of a fetal finger with a darkly stained, ossifying skeletal element and a small marrow space; connective tissue and skin outside.

Fetal phalanx, trichrome, zones of endochondral ossification from reserve zone to zone of erosion — **Medium magnification:** All zones in one image: from resting cartilage (bottom right) via columnar and hypertrophic cartilage to the zone of erosion with marrow space (top left).

Ossification front of fetal phalanx, trichrome, with cartilage zones, marrow cavity and bone collar — **Medium magnification:** Longitudinal section through the ossification front: hyaline cartilage on the left, then columnar and hypertrophic cartilage, primary marrow cavity with blood on the right; bone collar above and below.

Reserve zone of fetal phalanx, hyaline cartilage, trichrome, medium magnification — **Medium magnification:** Resting hyaline cartilage of the epiphysis (reserve zone): small, evenly distributed chondrocytes in pale turquoise matrix.

Bone collar, hypertrophic cartilage and primary marrow cavity, fetal phalanx, trichrome, medium magnification — **Medium magnification:** Beneath the periosteum lies the dark perichondral bone collar; below it hypertrophic cartilage with calcified septa and the primary marrow cavity with blood cells and trabeculae.

Bone trabeculae and marrow space at the edge of the fetal diaphysis, trichrome, medium magnification — **Medium magnification:** Peripheral diaphysis with bone trabeculae, marrow space with red blood cells and adjacent dense connective tissue; cartilage still visible at top left.

Hypertrophic cartilage and zone of erosion with calcified septa, fetal phalanx, trichrome, high magnification — **High magnification:** Transition from hypertrophic cartilage to the zone of erosion: lacunae are opened, and mesenchymal cells and red blood cells lie between dark green calcified septa.

Hypertrophic chondrocytes and calcified cartilage matrix, fetal phalanx, trichrome, very high magnification — **High magnification:** Hypertrophic cartilage at very high power: large chondrocytes; on the right the matrix between the cells has already calcified and stains darker.

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Assign the correct number in the image to each term.

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Multiple-choice questions on structure and function.

Frequently asked questions

Is the bone collar formed endochondrally or intramembranously?

Intramembranously: the periosteal osteoblasts form it directly without a cartilage stage. Endochondral ossification of a long bone therefore always involves both mechanisms side by side.

Why do hypertrophic chondrocytes die?

The surrounding matrix calcifies and impedes diffusion of nutrients; they are also actively driven into programmed cell death. Before that they secrete VEGF and thereby attract blood vessels.

When do the growth plates close?

At the end of puberty, controlled mainly by oestrogens. Bone then replaces the growth-plate cartilage and longitudinal growth stops; an epiphyseal scar often remains visible on X-ray.