6.7 bone formation

ossification or osteogenesis

process of bone formation

epiphyseal (growth) plate

a layer of hyaline cartilage in the metaphysis of a growing bone that consists of four zones

During infancy, childhood, and adolescence, bones throughout the body grow in thickness by_______________ _______________ and long bones lengthen by ____________________ ___________________.

appositional growth and interstitial growth

intramembranous ossification

bone forms directly within condensed mesenchyme, which is arranged in sheetlike layers that resemble membranes. (More simpler), the flat bones of the skull, most of the facial bones, mandible (lower jawbone), and the medial part of the clavicle (collar bone) are formed in this way

endochondral ossification

bone forms within hyaline cartilage that develops from mesenchyme.

soft spots

that help the fetal skull pass through the birth canal later harden as they undergo intramembranous ossification

remodeling of bone:

. Bone remodeling is the ongoing replacement of old bone tissue by new bone tissue. It involves bone resorption, the removal of minerals and collagen fibers from bone by osteoclasts, and bone deposition, the addition of minerals and collagen fibers to bone by osteoblasts. Thus, bone resorption results in the breakdown of bone extracellular matrix, and bone deposition results in its formation. About 5-10 percent of the total bone mass in the body is remodeled each year. The renewal rate for compact bone tissue is about 4 percent per year and for spongy bone tissue it is about 20 percent per year. Remodeling also takes place at different rates in different regions of the body. The distal portion of the femur is replaced about every four months. By contrast, bone in certain areas of the shaft of the femur will not be replaced completely during an individual's life. Even after bones have reached their adult shapes and sizes, old bone is continually destroyed and new bone is formed in its place. Remodeling also removes injured bone, replacing it with new bone tissue. Remodeling may be triggered by factors such as exercise, lifestyle modifications, and changes in diet.

Bone formation occurs in four principal situations:

(1) the initial formation of bones in an embryo and fetus, (2) the growth of bones during infancy, childhood, and adolescence until their adult sizes are reached, (3) the remodeling of bone (replacement of old bone by new bone tissue throughout life), and (4) the repair of fractures (breaks in bones) throughout life

remodeling bone benefits:

Remodeling has several other benefits. Since the strength of bone is related to the degree to which it is strained, if newly formed bone is subjected to heavy loads, it will grow thicker and therefore be stronger than the old bone. Also, the shape of a bone can be altered for proper support based on the strain patterns experienced during the remodeling process. Finally, new bone is more resistant to fracture than old bone.

remedies/medication for osteoporosis

Treatment options for osteoporosis are varied. With regard to nutrition, a diet high in calcium is important to reduce the risk of fractures. Vitamin D is necessary for the body to utilize calcium. In terms of exercise, regular performance of weight-bearing exercises has been shown to maintain and build bone mass. These exercises include walking, jogging, hiking, climbing stairs, playing tennis, and dancing. Resistance exercises, such as weight lifting, also build bone strength and muscle mass. Medications used to treat osteoporosis are generally of two types: (1) antireabsorptive drugs slow down the progression of bone loss, and (2) bone-building drugs promote increasing bone mass. Among the antireabsorptive drugs are (1) bisphosphonates, which inhibit osteoclasts (Fosamax®, Actonel®, Boniva®, and calcitonin); (2) selective estrogen receptor modulators, which mimic the effects of estrogens without unwanted side effects (Raloxifene®, Evista®); and (3) estrogen replacement therapy (ERT), which replaces estrogens lost during and after menopause (Premarin®), and hormone replacement therapy (HRT), which replaces estrogens and progesterone lost during and after menopause (Prempro®). ERT helps maintain and increase bone mass after menopause. Women on ERT have a slight increased risk of stroke and blood clots. HRT also helps maintain and increase bone mass. Women on HRT have increased risks of heart disease, breast cancer, stroke, blood clots, and dementia. Among the bone-building drugs is parathyroid hormone (PTH), which stimulates osteoblasts to produce new bone (Forteo®). Others are under development.

Paget's disease

here is an excessive proliferation of osteoclasts so that bone resorption occurs faster than bone deposition. In response, osteoblasts attempt to compensate, but the new bone is weaker because it has a higher proportion of spongy to compact bone, mineralization is decreased, and the newly synthesized extracellular matrix contains abnormal proteins. The newly formed bone, especially that of the pelvis, limbs, lower vertebrae, and skull, becomes enlarged, hard, and brittle and fractures easily. •

growth in length of a long bone:

involves (1) interstitial growth of cartilage on the epiphyseal side of the epiphyseal plate and (2) replacement of cartilage with bone by endochondral ossification on the diaphyseal side of the epiphyseal plate

The embryonic "skeleton" is at first composed of

mesenchyme in the general shape of bones; These become the sites where subsequent cartilage formation and then ossification occurs. (Recall that mesenchyme is a connective tissue found mostly in an embryo and is the tissue from which most other connective tissues develop.) This begins during the sixth week of embryonic development and follows one of two patterns.

Growth in thickness (appositional growth) steps

1. At the bone surface, periosteal cells differentiate into osteoblasts, which secrete the collagen fibers and other organic molecules that form bone extracellular matrix. The osteoblasts become surrounded by extracellular matrix and develop into osteocytes. This process forms bone ridges on either side of a periosteal blood vessel. The ridges slowly enlarge and create a groove for the periosteal blood vessel. 2. Eventually, the ridges fold together and fuse, and the groove becomes a tunnel that encloses the blood vessel. The former periosteum now becomes the endosteum that lines the tunnel. 3. Osteoblasts in the endosteum deposit bone extracellular matrix, forming new concentric lamellae. The formation of additional concentric lamellae proceeds inward toward the periosteal blood vessel. In this way, the tunnel fills in, and a new osteon is created. 4. As an osteon is forming, osteoblasts under the periosteum deposit new circumferential lamellae, further increasing the thickness of the bone. As additional periosteal blood vessels become enclosed as in step 1, the growth process continues.

endochondral ossification processes

1. Development of the cartilage model. At the site where the bone is going to form, specific chemical messages cause the cells in mesenchyme to crowd together in the general shape of the future bone, and then develop into chondroblasts. The chondroblasts secrete cartilage extracellular matrix, producing a cartilage model (future diaphysis) consisting of hyaline cartilage. A mesenchymal covering called the perichondrium (per-i-KON-drē-um) develops around the cartilage model. 2. Growth of the cartilage model.Once chondroblasts become deeply buried in the cartilage extracellular matrix, they are called chondrocytes. The cartilage model grows in length by continual cell division of chondrocytes, accompanied by further secretion of the cartilage extracellular matrix. This type of cartilaginous growth, called interstitial (endogenous) growth (growth from within), results in an increase in length. In contrast, growth of the cartilage in thickness is due mainly to the deposition of extracellular matrix material on the cartilage surface of the model by new chondroblasts that develop from the perichondrium in a process called appositional (exogenous) growth (a-pō-ZISH-i-nal), meaning growth of the outer surface (described shortly). As the cartilage model continues to grow, chondrocytes in its midregion hypertrophy (increase in size), and the surrounding cartilage extracellular matrix begins to calcify. Other chondrocytes within the calcifying cartilage die because nutrients can no longer diffuse quickly enough through the extracellular matrix. As these chondrocytes die, the spaces left behind by the dead chondrocytes merge into small cavities called lacunae. 3. Development of the primary ossification center. Primary ossification proceeds inward from the external surface of the bone. A nutrient artery penetrates the perichondrium and the calcifying cartilage model through a nutrient foramen in the midregion of the cartilage model, stimulating osteoprogenitor cells in the perichondrium to differentiate into osteoblasts. Once the perichondrium starts to form bone, it is known as the periosteum. Near the middle of the model, periosteal capillaries grow into the disintegrating calcified cartilage, inducing growth of a primary ossification center, a region where bone tissue will replace most of the cartilage. Osteoblasts then begin to deposit bone extracellular matrix over the remnants of calcified cartilage, forming spongy bone trabeculae. Primary ossification spreads from this central location toward both ends of the cartilage model. 4. Development of the medullary (marrow) cavity. As the primary ossification center grows toward the ends of the bone, osteoclasts break down some of the newly formed spongy bone trabeculae. This activity leaves a cavity, the medullary (marrow) cavity, in the diaphysis (shaft). Eventually, most of the wall of the diaphysis is replaced by compact bone. 5. Development of the secondary ossification centers. When branches of the epiphyseal artery enter the epiphyses, secondary ossification centers develop, usually around the time of birth. Bone formation is similar to what occurs in primary ossification centers. However, in the secondary ossification centers spongy bone remains in the interior of the epiphyses (no medullary cavities are formed here). In contrast to primary ossification, secondary ossification proceeds outward from the center of the epiphysis toward the outer surface of the bone. 6.Formation of articular cartilage and the epiphyseal (growth) plate. The hyaline cartilage that covers the epiphyses becomes the articular cartilage. Prior to adulthood, hyaline cartilage remains between the diaphysis and epiphysis as the epiphyseal (growth) plate, the region responsible for the lengthwise growth of long bones that you will learn about next

intramembranous ossification process

1. Development of the ossification center. At the site where the bone will develop, specific chemical messages cause the mesenchymal cells to cluster together and differentiate, first into osteoprogenitor cells and then into osteoblasts. The site of such a cluster is called an ossification center. Osteoblasts secrete the organic extracellular matrix of bone until they are surrounded by it. 2. Calcification. Next, the secretion of extracellular matrix stops and the cells, now called osteocytes, lie in lacunae and extend their narrow cytoplasmic processes into canaliculi that radiate in all directions. Within a few days, calcium and other mineral salts are deposited and the extracellular matrix hardens or calcifies (calcification). 3. Formation of trabeculae. As the bone extracellular matrix forms, it develops into trabeculae that fuse with one another to form spongy bone around the network of blood vessels in the tissue. Connective tissue that is associated with the blood vessels in the trabeculae differentiates into red bone marrow. 4. Development of the periosteum. In conjunction with the formation of trabeculae, the mesenchyme at the periphery of the bone condenses and develops into the periosteum. Eventually, a thin layer of compact bone replaces the surface layers of the spongy bone, but spongy bone remains in the center. Much of the newly formed bone is remodeled (destroyed and reformed) as the bone is transformed into its adult size and shape.

epiphyseal (growth) plate 4 zones and descriptions

1. Zone of resting cartilage. This layer is nearest the epiphysis and consists of small, scattered chondrocytes. The term resting is used because the cells do not function in bone growth. Rather, they anchor the epiphyseal plate to the epiphysis of the bone. 2. Zone of proliferating cartilage. Slightly larger chondrocytes arranged like stacks of coins undergo interstitial growth as they divide and secrete extracellular matrix. The chondrocytes in this zone divide to replace those that die at the diaphyseal side of the epiphyseal plate. 3. Zone of hypertrophic cartilage (hī-per-TRŌ-fik). This layer consists of large, maturing chondrocytes arranged in columns. 4 Zone of calcified cartilage. The final zone of the epiphyseal plate is only a few cells thick and consists mostly of chondrocytes that are dead because the extracellular matrix around them has calcified. Osteoclasts dissolve the calcified cartilage, and osteoblasts and capillaries from the diaphysis invade the area. The osteoblasts lay down bone extracellular matrix, replacing the calcified cartilage by the process of endochondral ossification. As a result, the zone of calcified cartilage becomes "new diaphysis" that is firmly cemented to the rest of the diaphysis of the bone.

intramembranous and endochondral ossification

The two methods of bone formation, which both involve the replacement of a preexisting connective tissue with bone, do not lead to differences in the structure of mature bones, but are simply different methods of bone development

orthodontics

is the branch of dentistry concerned with the prevention and correction of poorly aligned teeth. The movement of teeth by braces places a stress on the bone that forms the sockets that anchor the teeth. In response to this artificial stress, osteoclasts and osteoblasts remodel the sockets so that the teeth align properly.

Osteoporosis

iterally a condition of porous bones, affects 10 million people a year in the United States. In addition, 18 million people have low bone mass (osteopenia), which puts them at risk for osteoporosis. The basic problem is that bone resorption (breakdown) outpaces bone deposition (formation). In large part this is due to depletion of calcium from the body—more calcium is lost in urine, feces, and sweat than is absorbed from the diet. Bone mass becomes so depleted that bones fracture, often spontaneously, under the mechanical stresses of everyday living. For example, a hip fracture might result from simply sitting down too quickly. In the United States, osteoporosis causes more than one and a half million fractures a year, mainly in the hips, wrists, and vertebrae. Osteoporosis afflicts the entire skeletal system. In addition to fractures, osteoporosis causes shrinkage of vertebrae, height loss, hunched backs, and bone pain. Osteoporosis primarily affects middle-aged and elderly people, 80 percent of them women. Older women suffer from osteoporosis more often than men for two reasons: (1) Women's bones are less massive than men's bones, and (2) production of estrogens in women declines dramatically at menopause, whereas production of the main androgen, testosterone, in older men wanes gradually and only slightly. Estrogens and testosterone stimulate osteoblast activity and synthesis of bone matrix. Besides gender, risk factors for developing osteoporosis include a family history of the disease, European or Asian ancestry, thin or small body build, an inactive lifestyle, cigarette smoking, a diet low in calcium and vitamin D, more than two alcoholic drinks a day, and the use of certain medications. Osteoporosis is diagnosed by taking a family history and undergoing a bone mineral density (BMD) test. Performed like x-rays, BMD tests measure bone density. They can also be used to confirm a diagnosis of osteoporosis, determine the rate of bone loss, and monitor the effects of treatment. There is also a relatively new tool called FRAX® that incorporates risk factors besides bone mineral density to accurately estimate fracture risk. Patients fill out an online survey of risk factors such as age, gender, height, weight, ethnicity, prior fracture history, parental history of hip fracture, use of glucocorticoids (for example, cortisone), smoking, alcohol intake, and rheumatoid arthritis. Using the data, FRAX® provides an estimate of the probability that a person will suffer a fracture of the hip or other major bone in the spine, shoulder, or forearm due to osteoporosis within ten years.