My question is, for long bones like the femur, when exactly compact bone (cortical bone) starts to form and appear, before or after birth? In other words, it seems that compact bone formation occurs in parallel with development of secondary ossification centers as shown in the attached figure (Stage 4). Is this stage happening after birth or before that?
https://www.ncbi.nlm.nih.gov/books/NBK10056/
Chapter Bone Structure, Development and Bone Biology: Bone Pathology
Endochondral ossification involves the formation of cartilage tissue from aggregated mesenchymal cells and the subsequent replacement of this cartilage tissue by bone tissue. All of the skeletal components of the vertebral column, the pelvis, and the appendicular skeleton (limbs) develop via endochondoral ossification. The process of endochondral ossification is divided into five stages. First, the mesenchymal stem cells are committed to become cartilage cells through expression of two transcription factors, Pax1 and Scleraxis. These factors are thought to activate cartilage-specific genes. During the second phase of endochondral ossification, the committed mesenchymal stem cells condense into compact nodules and differentiate into chondrocytes. N-cadherin appears to be crucial for the initiation and maintenance of these condensations. In humans, the SOX9 gene (sex reversal Y-related high-mobility group box protein) and chondrocyte commitment, that encodes a DNA-binding protein, is expressed in the precartilaginous condensations. Mutation of the SOX9 gene alters skeletal development and results in deformities of most of bones of the body. Infants with specific mutations of the SOX9 gene die from respiratory failure due to poorly formed tracheal and rib cartilages. During the third phase of endochondral ossification, chondrocytes proliferate rapidly to form the cartilage model that will eventually be replaced by bone tissue. As they divide, chondrocytes secrete a cartilage-specific extracellular matrix. In the fourth phase, the chondrocytes stop dividing and become hypertrophic. Hypertrophic chondrocytes have increased production of collagen type X and fibronectin, thus altering the remaining cartilage matrix so that it can be mineralized by calcium carbonate. Finally, in the fifth phase, blood vessels begin the invasion of the cartilage model. The hypertrophic chondrocytes undergo apoptosis and the spaces are invaded by ingrowing blood vessels. As the cartilage cells die, osteoprogenitor cells differentiate into osteoblasts and begin to lay down bone matrix on the partially-degraded, mineralized cartilage remnants. The site at the center of the cartilaginous model where ossification first occurs is known as the primary center of ossification (the eventual diaphysis of the long bone). Eventually, all the cartilage is replaced by bone so the cartilage tissue serves as an intervening model for the bone that will eventually replace it. In experimental models, the precise sequence of events has been worked out reasonably well . In the long bones of mammals, this process of endochondral ossification spreads along the vertical axis of the developing bone in both directions from the primary ossification center. As the bones grow in length, secondary centers of ossification form at the ends of each bone. Once these secondary ossification centers form, there remains an area of cartilage between the primary and secondary ossifcation centers. The secondary ossification center becomes the epiphysis and the primary center becomes the diaphysis. The intervening cartilage is the epiphyseal growth plate and it is here that continued growth in length occurs at both ends of the developing bone. The epiphyseal plates contain three regions: a region of chondrocyte proliferation, a region of chondrocyte maturation, and a region of hypertrophic chondrocytes. A complex series of events occur in the growth plate as the resting chondrocytes proliferate, mature and become oriented in columns. As the cells hypertrophy at the expense of the intervening cartilaginous matrix, the cartilage matrix becomes calcified. It is these calcified cartilage remnants that then serve as a scaffold for the deposition of bone matrix by osteoblasts. The spaces left behind by the apopototic hypertrophic chondrocytes are invaded by blood vessels, a critical event in the formation of new bone tissue. Abnormalities in chondrocyte function can disrupt this sequence and produce abnormally short and misshapen bones. One illustration of this is achondroplasia, a condition causing short stature and thought to be caused by a mutation in fibroblast growth factor (FGF). Without the normal cellular processing of the signal from the fibroblast growth factor, the chondrocytes do not proliferate normally. This results in a disorganized and malfunctioning growth plate.
Thank you so much Sedat for the references and Entedhar for mentioning the related section.
I don't have much information in this area, but after looking at the references, it seems that mostly the process and sequences were explained and I could not find any clear timeline regarding cortical bone formation and whether it happens during embryonic development or after birth.
Briefly, I want to know, is there any cortical bone in the long bones right before birth?
None shows up on Xray from long bones in a human infant at birth, so based on this observation, I would say no not before birth.
Thanks Lenard for your answer.
Just to make sure, is this timeline the same for compact bone formation in both diaphysis and epiphysis of the femur? In other words, are they both forming after birth? And do you know any reference in which I can find this information?
Hi,
if I understand your question correctly, the answer is that there is a cortical bone present before birth; see attached screenshot for the femur from Juvenile osteology: a laboratory field manual by Schaefer, Black and Scheuer (2009).
This book can be useful starting point because it contains a lot of references and tables with dry bone measurements for age estimation for fetal, infant and juvenile skeletons. Hope it helps
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