Intramembranous Ossification

During intramembranous ossification, compact and spongy bone develops directly from sheets of connective tissue. The flat bones of the face, most of the cranial bones, and the clavicles (collarbones) are formed via intramembranous ossification.

Osteoblasts secrete osteoid, uncalcified matrix consisting of collagen precursors and other organic proteins, which calcifies (hardens) within a few days as mineral salts are deposited on it, thereby entrapping the osteoblasts within. Once entrapped, the osteoblasts become osteocytes (Figure 6.4.1b). As osteoblasts transform into osteocytes, osteogenic cells in the surrounding connective tissue differentiate into new osteoblasts at the edges of the growing bone.

Several clusters of osteoid unite around the capillaries to form a trabecular matrix, while osteoblasts on the surface of the newly formed spongy bone become the cellular layer of the periosteum (Figure 6.4.1c). The periosteum then secretes compact bone superficial to the spongy bone. The spongy bone crowds nearby blood vessels, which eventually condense into red bone marrow (Figure 6.4.1d). The new bone is constantly also remodeling under the action of osteoclasts (not shown).

Intramembranous ossification begins in utero during fetal development and continues on into adolescence. At birth, the skull and clavicles are not fully ossified nor are the junctions between the skull bone (sutures) closed. This allows the skull and shoulders to deform during passage through the birth canal. The last bones to ossify via intramembranous ossification are the flat bones of the face, which reach their adult size at the end of the adolescent growth spurt.

Endochondral Ossification

In endochondral ossification, bone develops by replacing hyaline cartilage. Cartilage does not become bone. Instead, cartilage serves as a template to be completely replaced by new bone. Endochondral ossification takes much longer than intramembranous ossification. Bones at the base of the skull and long bones form via endochondral ossification.

As more and more matrix is produced, the cartilaginous model grow in size. Blood vessels bring osteoblasts to the edges of the structure and these arriving osteoblasts deposit bone in a ring around the diaphysis – this is called a bone collar (Figure 6.4.2b). The bony edges of the developing structure prevent nutrients from diffusing into the center of the hyaline cartilage. This results in chondrocyte death and disintegration in the center of the structure. Without cartilage inhibiting blood vessel invasion, blood vessels penetrate the resulting spaces, not only enlarging the cavities but also carrying osteogenic cells with them, many of which will become osteoblasts. These enlarging spaces eventually combine to become the medullary cavity. Bone is now deposited within the structure creating the primary ossification center (Figure 6.4.2c).

While these deep changes are occurring, chondrocytes and cartilage continue to grow at the ends of the structure (the future epiphyses), which increases the structure’s length at the same time bone is replacing cartilage in the diaphyses. This continued growth is accompanied by remodeling inside the medullary cavity (osteoclasts were also brought with invading blood vessels) and overall lengthening of the structure (Figure 6.4.2d). By the time the fetal skeleton is fully formed, cartilage remains at the epiphyses and at the joint surface as articular cartilage.

After birth, this same sequence of events (matrix mineralization, death of chondrocytes, invasion of blood vessels from the periosteum, and seeding with osteogenic cells that become osteoblasts) occurs in the epiphyseal regions, and each of these centers of activity is referred to as a secondary ossification center (Figure 6.4.2e). Throughout childhood and adolescence, there remains a thin plate of hyaline cartilage between the diaphysis and epiphysis known as the growth or epiphyseal plate (Figure 6.4.2f). Eventually, this hyaline cartilage will be removed and replaced by bone to become the epiphyseal line.

How Bones Grow in Length

The epiphyseal plate is the area of elongation in a long bone. It includes a layer of hyaline cartilage where ossification can continue to occur in immature bones. As cartilage grows, the entire structure grows in length and then is turned into bone. Once cartilage cannot grow further, the structure cannot elongate more.

Bones continue to grow in length until early adulthood. The rate of growth is controlled by hormones, which will be discussed later. When the chondrocytes in the epiphyseal plate cease their proliferation and bone replaces all the cartilage, longitudinal growth stops. All that remains of the epiphyseal plate is the ossified epiphyseal line (Figure 6.4.4).

How Bones Grow in Diameter

While bones are increasing in length, they are also increasing in diameter; growth in diameter can continue even after longitudinal growth ceases. This growth can occur at the endosteum or peristeum where osteoclasts resorb old bone that lines the medullary cavity, while osteoblasts produce new bone tissue. The erosion of old bone along the medullary cavity and the deposition of new bone beneath the periosteum not only increase the diameter of the diaphysis but also increase the diameter of the medullary cavity. This remodeling of bone primarily takes place during a bone’s growth. However, in adult life, bone undergoes constant remodeling, in which resorption of old or damaged bone takes place on the same surface where osteoblasts lay new bone to replace that which is resorbed. Injury, exercise, and other activities lead to remodeling. Those influences are discussed later in the chapter, but even without injury or exercise, about 5 to 10 percent of the skeleton is remodeled annually just by destroying old bone and renewing it with fresh bone.