Bone is a replacement tissue; that is, it uses a model tissue as a template on which to lay down its mineral matrix. In the early stages of embryonic development, the embryo’s skeleton consists of fibrous membranes (made out of sheets of mesenchymal (undifferentiated) connective tissue) and hyaline cartilage. By the sixth or seventh week of embryonic life, the actual process of bone development, ossification, begins in which the fibrous membranes and hyaline cartilage are replaced by bone.

By the time a fetus is born, all fibrous membranes and most of the cartilage has been replaced with bone. Some additional cartilage will be replaced throughout childhood, and some cartilage remains in the adult skeleton.

There are two bone development pathways — intramembranous ossification and endochondral ossification — but bone is the same regardless of the pathway that produces it.

Intramembranous Ossification

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

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.

In a long bone, for example, at about 6 to 8 weeks after conception, some of the mesenchymal cells differentiate into chondrocytes (cartilage cells) that form the cartilaginous skeletal precursor of the bones (Figure 5.13 a).

As more matrix is produced, the chondrocytes in the center of the cartilaginous model grow in size. As the matrix calcifies, nutrients can no longer reach the chondrocytes (Figure 5.13 b). This results in their death and the disintegration of the surrounding cartilage. Blood vessels (capillaries) invade 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.

The penetration of capillaries initiates the transformation of the perichondrium into the bone-producing periosteum. Here, the osteoblasts form a periosteal collar of compact bone around the cartilage of the diaphysis. By the second or third month of fetal life, bone cell development and ossification ramps up and creates the primary ossification center, a region deep in the periosteal collar where ossification begins (Figure 5.13 c).

While these deep changes are occurring, chondrocytes and cartilage continue to grow at the ends of the bone (the future epiphyses), which increases the bone’s length at the same time bone is replacing cartilage in the diaphyses (Figure 5.13 d). By the time the fetal skeleton is fully formed, cartilage only remains at the joint surface as articular cartilage and between the diaphysis and epiphysis as the epiphyseal plate, the latter of which is responsible for the longitudinal growth of bones. 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 5.13 e).

How Bones Grow in Length

The epiphyseal plate is the area of growth in a long bone. It is a layer of hyaline cartilage where ossification occurs in immature bones. On the epiphyseal side of the epiphyseal plate, cartilage is formed. On the diaphyseal side, cartilage is ossified, and the diaphysis grows in length. Bones continue to grow in length until early adulthood. When the chondrocytes in the epiphyseal plate cease their proliferation and bone replaces the cartilage, longitudinal growth stops. All that remains of the epiphyseal plate is the epiphyseal line (Figure 5.14).

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 is called appositional growth. Osteoclasts resorb old bone that lines the medullary cavity, while osteoblasts, via intramembranous ossification, produce new bone tissue beneath the periosteum. 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 process is called modeling.

Bone Remodeling

The process in which matrix is resorbed on one surface of a bone and deposited on another is known as bone modeling. Modeling primarily takes place during a bone’s growth. However, in adult life, bone undergoes 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. 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.

Section Summary

All bone formation is a replacement process. Embryos develop a cartilaginous skeleton and various membranes. During development, these are replaced by bone during the ossification process. In endochondral ossification, bone develops by replacing hyaline cartilage. Activity in the epiphyseal plate enables bones to grow in length. Modeling allows bones to grow in diameter. Remodeling occurs as bone is resorbed and replaced by new bone. Osteogenesis imperfecta is a genetic disease in which collagen production is altered, resulting in fragile, brittle bones.