Fetal bone formation occurs by either endochondral ossification (i.e., from a cartilage template) or by intra-membranous ossification (i.e., without a cartilage precursor). Most mammalian fetal bone is formed via endo-chondral ossification, but intramembranous ossification forms bones of the skull. The fetal skull is developed when osteoblasts in connective tissue begin producing collagen fibers and bone matrix. The osteoblasts ultimately differentiate into osteocytes and produce bone. The cartilage template of the axial and appendicular skeleton formed during the embryonic phase is gradually replaced by ossification of the cartilage model. The chondrocytes die as the cartilage matrix becomes ossified by activity of chondrocytes themselves, as well as by osteoblasts and osteocytes of developing bone. Ossification of the diaphysis (shaft) of long bones begins in the center and progresses toward each end to form compact bone. Ossification of the epiphysis (head) of long bones and in the axial skeleton is less extensive, resulting in spongy bone. At birth, most of the cartilage has been replaced by bone. However, cartilage remains in the intervertebral disks, dorsal surfaces of the vertical processes of vertebrae, articular surfaces, and the epiphyseal plate of long bones.
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