Growth and Development of Bones

Growth and Development of Bones

Bones begin to form in utero during the first eight weeks after fertilization. Intramembranous bones originate between layers of connective tissues that are sheet-like in appearance. Examples of intramembranous bones are the flat, broad bones of the skull. These bones, also called dermal bones, begin development when unspecialized connective tissues form at the sites where future bones will be developed. Bone-forming cells (osteoblasts) develop, depositing bony matrix around them. When extracellular matrix has sur-rounded the osteoblasts, they are termed osteocytes. The surrounding membranous tissues begin to form the periosteum of a bone. Inside the periosteum, the osteoblasts form a compact bone layer over the new spongy bone.

Endochondral bones begin as cartilaginous masses that are eventually replaced by bone tissue. These bones develop from hyaline cartilage that is shaped similarly to the bones they will become (­FIGURE 7-6). They grow rapidly at first, and then begin to change in appearance. When spongy bone begins to replace the original cartilage, a primary ossification center is created, with bone tissue developing outward toward the ends of the structure. Eventually, secondary ossifi-cation centers appear in the epiphyses, forming more spongy bone.

During the first eight weeks of development, the skeleton is cartilaginous. The bones increase greatly in size as the fetus develops and throughout childhood (FIGURE 7-7). Bone growth continues through adoles-cence. The process of replacing other tissues with bone is called ossification, which involves the deposition of calcium salts. In embryos, ossification (as well as osteogenesis) leads to formation of the skeleton. Later in development, bone growth occurs until early adult-hood. Throughout life, the bones can become thicker. Osteogenesis is defined as the formation of bone.

The skeleton of a human embryo, before week eight of gestation, is made of fibrous membranes and hyaline cartilage. At week 8, bone tissue begins to develop, replacing most existing cartilage or fibrous structures over time. For example, the long bones are first formed of hyaline cartilage and later replaced by bony tissue that becomes compact bone. This process begins with the diaphysis and ends with the epiphyses of each long bone. This process of bone formation is called ­endochondral ossification. Cartilage is also referred to as endochondral bone.

Nearly all bones below the base of the skull (except the clavicles) are formed by endochondral ossification. At month two of gestation, hyaline cartilages previously formed are used as models for actual bones. Endochon-dral ossification is more complicated than intramem-branous ossification, because hyaline cartilage is broken down while ossification is occurring. For long bones, the center of a hyaline cartilage shaft (the primary ossification center) is where ossification begins. Blood vessels­ form in the perichondrium that covers the ­hyaline ­cartilage bone model and convert it to a vascu-larized periosteum. As nutrients become more plenti-ful, underlying mesenchymal cells specialize to become osteoblasts. This becomes the basis for ossification.

Bone collars form around the diaphysis of the hyaline cartilage models, as osteoblasts secrete osteoid against the hyaline cartilage diaphysis. They enclose it in a collar-like structure known as the periosteal bone collar. In the center of the diaphysis, the cartilage cal-cifies, developing cavities. Chondrocytes in the shaft enlarge (hypertrophy), which leads to the surrounding cartilage matrix to calcify. Because this matrix cannot be penetrated by diffusing nutrients, chondrocytes die. The matrix deteriorates, opening up cavities. The bone collar stabilizes the hyaline cartilage model. In other locations, the cartilage is still healthy and grow-ing quickly, which lengthens the cartilage model.

By the third month, the cavities are invaded by elements, collectively known as the periosteal bud. This contains a nutrient artery and vein, red marrow elements, nerve fibers, osteoclasts, and osteogenic cells. The calcified cartilage matrix is partially eroded by the osteoclasts. The osteogenic cells become osteo-blasts, secreting osteoid around calcified fragment of hyaline cartilage. This forms a bone-covered cartilage trabeculae. Therefore, an early version of spongy bone develops in the long bone.

Osteoclasts break down the new spongy bone as the primary ossification center enlarges. A med-ullary cavity is opened in the center of the diaphy-sis. From week nine until birth, the quickly growing epiphyses are made only of cartilage. The hyaline car-tilage models continue lengthening via the division of viable cartilage cells at the epiphyses. Down the length of the shaft, cartilage calcifies, erodes, and is replaced by spiked bone structures on epiphyseal surfaces that face the medullary cavity.

At birth, most long bones have a bony diaphysis that surrounds spongy bone remnants, a medullary cavity that is widening, and two epiphyses made of cartilage. Secondary ossification centers develop in one or both epiphyses just before or just after birth. Usually, secondary centers form in both epiphyses of larger long bones, and in smaller long bones, usually only one secondary ossification center forms. The cen-tral cartilage of the epiphysis calcifies and deteriorates. Cavities open, allowing a periosteal bud to enter. Bone trabeculae appear similar to how they appeared in the primary ossification center. Short bones develop dif-ferently in that only the primary ossification center is formed, and most irregular bones have several distinct ossification centers from which they develop.

Secondary ossification is very similar to primary ossification, except for interior spongy bone being retained and the lack of a medullary cavity being formed in the epiphyses. Hyaline cartilage remains only on the epiphyseal surfaces (as articular cartilages) and at the junction of diaphyses and epiphyses (forming epiphy-seal plates) when secondary ossification is complete.

Flat bones are not formed in the same way as long bones. Flat bones develop from fibrous connective tissue membranes (formed by mesenchymal cells) that are replaced by spongy bone, and then compact bone in a process is called intramembranous ossifica-tion. The produced bones are also referred to as mem-brane bones. In the embryonic skeleton, membranes and cartilages allow for mitosis. Examples of flat bones formed via intramembranous ossification include the frontal, parietal, occipital, and temporal bones of the skull and the clavicles. Ossification begins at about week eight of gestation.

When the bones are growing, the diaphyses meet the epiphyses at a structure called the epiphyseal plate. It is made of four cartilage layers: reserve cartilage, prolifer-ating (hyperplastic) cartilage, hypertrophic cartilage, and the calcified matrix. Growth of long bones depends on good nutrition and several hormones, including human growth hormone. Interstitial growth of the epiphyseal plate cartilage and then replacement by bone is responsi-ble for all long bone growth after birth. All bones grow in thickness by appositional growth. The other hormones involved in long bone growth include thyroid hormone, estrogen, and testosterone. Once the epiphyseal plate experiences closure, the long bones can no longer grow (­FIGURE 7-8). Length of bone is balanced by increased bone width. Osteoblast and osteoclast activity is balanced in the body, so bones grow with uniformity. Most bone growth stops during adolescence, although the bones of the nose and lower jaw (as well as other facial bones) may continue to grow in only tiny increments throughout life.

Bone development, growth, and repair are influenced by nutrition, hormones, and exercise. ­Vitamin D is required for the absorption of calcium in the small intestine. Without it, calcium is not absorbed well, softening bones and potentially causing defor-mity. Growth hormone from the anterior pituitary gland stimulates cell division in the epiphyseal plates. During infancy and childhood, growth hormone from the anterior pituitary gland determines epiphyseal plate growth activity. This hormone is modulated by thyroid hormones, so the skeleton develops the proper proportions during growth. Calcitriol, syn-thesized from another steroid called cholecalciferol (vitamin D₃), is made by the kidneys. It is essential for normal phosphate and calcium ion absorption in the digestive tract. Cholecalciferol is produced in the skin or absorbed from the diet. Vitamin C must also be present in the diet, because it is needed for import-ant enzyme reactions in collagen synthesis and to stimulate osteoblast differentiation. Vitamin A stimulates osteoblast activity and vitamins C, K, and B₁₂ are essential for synthesis of normal bone proteins.

At puberty, male and female sex hormones (testosterone and estrogen, respectively) stimulate ossification of these plates. Thyroid hormone modulates the activity of growth hormone. Exercise stresses the bones, stimulating them to become these hormones. If growth hormone is excessively secreted, gigantism occurs. Similarly, hormone deficits result in various forms of dwarfism.

1. Explain how bones begin to form.

2. Describe the location of the primary and secondary ossification centers in long bones.

3. What is the role of mesenchymal cells?

4. What types of nutrition and hormones influence bone development and growth?