In the early stages of development, the skeleton consists of fibrous membranes and hyaline cartilage. By the sixth or seventh week of life in the womb, the actual process of bone development, ossification (osteogenesis), begins. There are two pathways that osteogenesis can take:
Intramembranous Ossification
Endochondral Ossification
In either case, compact and spongy bone is the same regardless of the pathway that produces it.
Bone is a replacement tissue; that is, it uses a model tissue on which to lay down its mineral matrix. For skeletal development, the most common template is cartilage. During development, a framework is laid down that determines where bones will form. This framework is a flexible, semi-solid matrix produced by chondroblasts. Recall that chondroblasts are the cells from cartilage that produce the extracellular matrix. As the matrix surrounds and isolates chondroblasts, they are called chondrocytes.
key concept
Unlike most connective tissues, cartilage is avascular, meaning that it has no blood vessels supplying nutrients and removing metabolic wastes. All of these functions are carried on by diffusion through the matrix. This is why damaged cartilage does not repair itself as readily as most tissues do.
Up through childhood growth and development, bone forms from a cartilage model. By birth, 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 forever.
term to know
Ossification
The process of bone formation.
2. Intramembranous Ossification
During intramembranous ossification, compact and spongy bone develops directly from sheets of undifferentiated connective tissue (intra, inside; membranous, membrane). The flat bones of the face, most of the skull bones, and the collarbones (clavicles) are formed via intramembranous ossification. These bones form in four steps.
step by step
1. Form ossification center. The cells in the embryonic skeleton gather together and begin to differentiate (specialize). Some will differentiate into capillaries, while others will become osteogenic cells and then osteoblasts. Although they will ultimately be spread out by the formation of bone tissue, early osteoblasts appear in a cluster called an ossification center.
2. Form osteocytes. The osteoblasts secrete osteoid, uncalcified bone matrix which calcifies (hardens) within a few days as mineral salts are deposited on it and thereby entrapping the osteoblasts within. Once entrapped, the osteoblasts become osteocytes. As osteoblasts transform into osteocytes, osteogenic cells in the surrounding connective tissue differentiate into new osteoblasts.
3. Form trabeculae and periosteum. Osteoid (unmineralized bone matrix) secreted around the capillaries results in a trabecular matrix, while osteoblasts on the surface of the spongy bone become the periosteum.
4. Form compact bone and red bone marrow. The periosteum then creates a protective layer of compact bone superficial to the trabecular bone. The trabecular bone crowds nearby blood vessels, which eventually condense into red bone marrow.
Intramembranous Ossification - Intramembranous ossification follows four steps. (a) Undifferentiated connective tissue cells group into clusters and ossification centers form. (b) Secreted osteoid traps osteoblasts, which then become osteocytes. (c) Trabecular matrix and periosteum form. (d) Compact bone develops superficial to the trabecular bone, and crowded blood vessels condense into red bone marrow.
Intramembranous ossification begins in utero (in the uterus) during early development and continues on into adolescence. At birth, the skull and clavicles are not fully ossified nor are the sutures of the skull closed. This allows the skull and shoulders to deform during passage through the birth canal. The last bones to ossify by intramembranous ossification are the flat bones of the face, which reach their adult size at the end of the adolescent growth spurt.
terms to know
Intramembranous Ossification
The process of bone formation from undifferentiated connective tissue.
Ossification Center
A cluster of early osteoblasts.
Osteoid
Uncalcified bone matrix produced and secreted by osteoblasts.
3. Endochondral Ossification
In endochondral ossification, bone develops by replacing hyaline cartilage (endo, inside; chondral, cartilage). Cartilage does not become bone, but instead 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. These bones form in 4 steps.
step by step
a. Form chondrocytes and perichondrium. In a long bone, for example, at about 6 to 8 weeks after conception, some of the cells differentiate into chondrocytes that form the early skeleton. Soon after, the perichondrium, a membrane that covers the cartilage (peri, around), appears.
b. Form medullary cavity. As more matrix is produced, the chondrocytes in the center of the tissue grow in size. As the matrix calcifies, nutrients can no longer reach the chondrocytes. This results in their death and the disintegration of the surrounding cartilage. These enlarging spaces eventually combine to become the medullary cavity.
c. Form primary ossification center. As the cartilage grows, blood vessels penetrate it, initiating two transformations. First, the perichondrium becomes the bone-producing periosteum (osseous, bone). Here, osteogenic cells transported in by the blood vessels turn into osteoblasts and form a periosteal collar of compact bone around the cartilage of the diaphysis. Second, by the second or third month of life in the womb, bone production ramps up deep inside forming the primary ossification center. This region of ossification expands to convert the diaphysis to osseous (bone) tissue and reaches out to both epiphyses (singular, epiphysis).
d. Form secondary ossification center. After birth, the same sequence of events (matrix mineralization, death of chondrocytes, invasion of blood vessels, and seeding with osteogenic cells that become osteoblasts) occurs in the epiphyseal region as what is called the secondary ossification center. Cartilage will then remain in two locations. Between the diaphysis and epiphysis, the epiphyseal cartilage or plate is responsible for bone growth in length but converts to bone tissue during puberty. At the joint (articular) surface, articular cartilage smooths joint movement for life or until damaged or diseased.
Endochondral Ossification - Endochondral ossification follows four steps. (a) Cells differentiate into chondrocytes. (b) The cartilage model of the future bony skeleton and the perichondrium form. (c1) Capillaries penetrate cartilage. Perichondrium transforms into periosteum. Primary ossification center develops. (c2) Cartilage and chondrocytes continue to grow at the ends of the bone. (d1) Secondary ossification centers develop. (d2) Cartilage remains at the epiphyseal (growth) plate and at the joint surface as articular cartilage.
terms to know
Endochondral Ossification
The process of bone formation by replacement of hyaline cartilage.
Perichondrium
A membrane that covers the surface of cartilage.
Primary Ossification Center
The initial site of osteogenesis during endochondral ossification, located in the diaphysis.
Secondary Ossification Center
The second site of osteogenesis during endochondral ossification, located in the future epiphyses.
4. How Bones Grow in Length
The epiphyseal (growth) plate is responsible for the longitudinal growth (growth in length) of a long bone, called interstitial growth. In this border between the diaphysis and an epiphysis, a layer of hyaline cartilage is present. On the epiphyseal side of the epiphyseal plate, cartilage is formed by division of chondrocytes and continued production of matrix. On the diaphyseal side, cartilage is ossified. Together, these two processes work at similar paces, continually shifting the epiphysis and epiphyseal plate. Since this process occurs at both ends of the bone—both the proximal and distal epiphysis—the result is the lengthening of the diaphysis and bone.
The epiphyseal plate is composed of four zones of cells and activity. Each zone represents changes that occur in the cartilage prior to bone matrix being deposited.
The reserve zone is the region closest to the epiphyseal end of the plate and contains small chondrocytes within the matrix. These chondrocytes do not participate in bone growth but function like glue, securing the epiphyseal plate to the osseous tissue of the epiphysis so they don’t separate from each other.
The proliferative zone is the next layer toward the diaphysis. This layer contains stacks of slightly larger chondrocytes and is proliferative, meaning it undergoes mitosis (cell division) to produce new chondrocytes. The chondrocytes this layer produces will replace those that die at the diaphyseal end of the plate.
The zone of maturation and hypertrophy contains older chondrocytes that are able to mature (no longer undergo mitosis). Additionally, these cells begin to calcify (harden with calcium deposits) the matrix around them.
The zone of calcified matrix contains calcified matrix and dead chondrocytes.
Longitudinal Bone Growth - The epiphyseal plate is responsible for longitudinal bone growth.
Blood vessels penetrate the calcified matrix, delivering osteogenic cells which turn into osteoblasts and secrete bone tissue. This region is called the zone of ossification. As the cartilage expands on the epiphyseal side and the zone of ossification continues to deposit bone matrix into the calcified matrix, the diaphysis continues to grow in length.
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 zones of the epiphyseal plate, longitudinal growth stops. The epiphyseal plate then completely converts to bone, becoming the epiphyseal line, a dense region of osseous tissue separating the diaphysis and epiphysis. An X-ray of this region shows the presence of an epiphyseal plate or line and can be used to determine whether a bone is done growing or not as well as its approximate age.
Progression from Epiphyseal Plate to Epiphyseal Line - As a bone matures, the epiphyseal plate progresses to an epiphyseal line. (a) Epiphyseal plates are visible in a growing bone. (b) Epiphyseal lines are the remnants of epiphyseal plates in a mature bone. (c) Epiphyseal plates show up on X-rays as dark gaps in the bone. (d) Epiphyseal lines show up on X-rays as bright bone.
terms to know
Interstitial Growth
Growth of a long bone in length.
Reserve Zone
The zone of an epiphyseal plate closest to the epiphysis which contains small, non-proliferative chondrocytes.
Proliferative Zone
The zone of an epiphyseal plate next to the reserve zone which contains expanding, proliferative chondrocytes.
Zone of Maturation and Hypertrophy
The zone of an epiphyseal plate which contains large, non-proliferative chondrocytes.
Zone of Calcified Matrix
The zone of an epiphyseal plate closest to the diaphysis which contains calcified matrix and dead chondrocytes.
Zone of Ossification
The region of a growing diaphysis where bone matrix is being deposited.
5. How Bones Grow in Diameter
While bones are increasing in length, they are also increasing in diameter, called appositional growth. Growth in diameter can continue even after longitudinal growth ceases.
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.
Appositional Growth - Appositional growth is the growth of a bone in width. Osseous (bone) tissue from the center of the bone is removed on the inside by osteoclasts while new osseous tissue is added on the outside by osteoblasts.
terms to know
Appositional Growth
Growth of a long bone in width.
Modeling
The process, during bone growth, by which bone is resorbed on one surface of a bone and deposited on another.
6. Bone Remodeling
Bone modeling primarily takes place during a bone’s growth—during development. 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. Even without injury or exercise, about 5 to 10% of the skeleton is remodeled annually just by destroying old bone and renewing it with fresh bone.
term to know
Remodeling
The process, after bone growth, by which bone is resorbed and deposited on the same surface.
summary
In this lesson, you learned about how bones are formed and developed. You learned that bones are initially formed as cartilage templates and how bones are formed by either intramembranous ossification or endochondral ossification. You also learned about how bones grow in length and diameter. Lastly, you learned how bones undergo bone remodeling after development is complete.
