Chapter 7 - Skeletal System: Bone Structure and Function

Appositional growth of cartilage

Appositional growth is an increase in width along the cartilage's outside edge, or periphery. The following three steps occur in this process (figure 7.9b): • 1 Undifferentiated stem cells at the internal edge of the perichondrium begin to divide. (Note the perichondrium contains mesenchymal cells as well as these stem cells.) • 2 New undifferentiated stem cells and committed cells that differentiate into chondroblasts are formed. These chondroblasts are located at the periphery of the old cartilage, where they begin to produce and secrete new cartilage matrix. • 3 The chondroblasts, as a result of matrix formation, push apart and become chondrocytes, with each occupying its own lacuna. The cartilage continues to grow at the periphery as chondrocytes continue to produce more matrix. During early embryonic development, both interstitial and appositional cartilage growth occur simultaneously. Note that interstitial growth declines rapidly as the cartilage matures because the cartilage becomes semirigid, and it is no longer able to expand. Further growth can occur only at the periphery of the tissue, so later growth is primarily appositional. Once the cartilage is fully mature, new cartilage growth typically stops. Thereafter, cartilage growth usually occurs only after injury to the cartilage, yet this growth is limited due to the lack of blood vessels in the tissue.

the five zones of the epiphyseal plate, describe how growth in length occurs there

As with cartilage growth, a long bone's growth in length is called interstitial growth, and its growth in diameter or thickness is termed appositional growth. Interstitial Growth Interstitial growth is dependent upon growth of cartilage within the epiphyseal plate. The epiphyseal plate exhibits five distinct microscopic zones that are continuous from the first zone nearest the epiphysis to the last zone nearest the diaphysis (figure 7.12): • 1. Zone of resting cartilage. This zone is farthest from the medullary cavity of the diaphysis and nearest the epiphysis. It is composed of small chondrocytes distributed throughout the cartilage matrix. It resembles mature and healthy hyaline cartilage. This region secures the epiphysis to the epiphyseal plate. • 2. Zone of proliferating cartilage. Chondrocytes in this zone undergo rapid mitotic cell division, enlarge slightly, and become aligned like a stack of coins into longitudinal columns of flattened lacunae. These columns are parallel to the diaphysis. • 3. Zone of hypertrophic cartilage. Chondrocytes cease dividing and begin to hypertrophy (enlarge in size) in this zone. The walls of the lacunae become thin because the chondrocytes resorb matrix as they hypertrophy. • 4. Zone of calcified cartilage. This zone usually is composed of 2 to 3 layers of chondrocytes. Minerals are deposited in the matrix between the columns of lacunae; this calcification destroys the chondrocytes and makes the matrix appear opaque. • 5. Zone of ossification. The walls break down between lacunae in the columns, forming longitudinal channels. These spaces are invaded by capillaries and osteoprogenitor cells from the medullary cavity. New matrix of bone is deposited on the remaining calcified cartilage matrix.

Bone Matrix: Its Formation and Resorption

Bone Matrix: Its Formation and Resorption • Bone formation begins when osteoblasts secrete the initial semisolid organic form of bone matrix called osteoid. • Calcification, or mineralization, subsequently occurs to the osteoid when hydroxyapatite crystals deposit in the bone matrix. • Calcification is initiated when the concentration of calcium ions and phosphate ions reach critical levels and precipitate out of solution, thus forming the hydroxyapatite crystals that deposit in and around the collagen fibers. • The entire process of bone formation requires a number of substances, including vitamin D (which enhances calcium absorption from the gastrointestinal tract) and vitamin C (which is required for collagen formation), as well as calcium and phosphate for calcification. • Bone resorption is a process whereby bone matrix is destroyed by substances released from osteoclasts into the extracellular space adjacent to the bone. • Proteolytic enzymes released from lysosomes within the osteoclasts chemically digest the organic components (collagen fibers and proteoglycans) of the matrix, while hydrochloric acid (HCl) dissolves the mineral parts (calcium and phosphate) of the bone matrix. • The liberated calcium and phosphate ions enter the blood. Bone resorption may occur when blood calcium levels are low (described in detail in section 7.6b).

Compact Bone Microscopic Anatomy Compact bone

Comparison of Compact and Spongy Bone Microscopic Anatomy • Compact bone and spongy bone have unique and differing microscopic architecture (figure 7.7). Compact Bone Microscopic Anatomy Compact bone is composed of small cylindrical structures called osteons, or Haversian systems. An osteon is the basic functional and structural unit of mature compact bone (figure 7.7a, b). Osteons are oriented parallel to the diaphysis of the long bone. When an osteon is viewed in cross section, it has the appearance of a bull's-eye target. An osteon has several components as follows: • The central (Haversian) canal is a cylindrical channel that lies in the center of the osteon and runs parallel to it. Extending through the central canal are the blood vessels and nerves that supply the bone. • Concentric lamellae are rings of bone connective tissue that surround the central canal and form the bulk of the osteon. The numbers of concentric lamellae vary among osteons. Each lamella contains collagen fibers oriented at an angle in one direction; adjacent lamellae contain collagen fibers oriented at an angle that is 90 degrees different from both the previous and next lamellae. This alternating pattern of collagen fiber direction gives bone part of its strength and resilience. • Osteocytes are mature bone cells found in small spaces (see next) between adjacent concentric lamellae. These cells maintain the bone matrix. • Lacunae are the small spaces that each house an osteocyte. • Canaliculi are tiny, interconnecting channels within the bone connective tissue that extend from each lacuna, travel through the lamellae, and connect to other lacunae and the central canal. Canaliculi house osteocyte cytoplasmic projections that permit intercellular contact and communication. Nutrients, minerals, gases, and wastes are transported through the cytoplasmic extensions within these passageways, allowing their exchange between the blood vessels of the central canal and the osteocytes. Figure 7.8 shows cross sections of osteons as viewed through a light microscope and a scanning electron microscope. Several other structures occur in compact bone, but are not part of the osteon proper, including the following (see figure 7.7a): • Perforating (Volkmann) canals resemble central canals in that they also contain blood vessels and nerves. However, perforating canals run perpendicular to the central canals and help connect multiple central canals within different osteons, thus forming a vascular and innervation connection among the multiple osteons. • Circumferential lamellae are rings of bone immediately internal to the periosteum of the bone (external circumferential lamellae) or internal to the endosteum (internal circumferential lamellae). Both external and internal circumferential lamellae run the entire circumference of the bone itself (hence, their name). • Interstitial lamellae (interstitial systems) are either the components of compact bone that are between osteons or are the leftover parts of osteons that have been partially resorbed—thus they often look like a "bite" has been taken out of them. The interstitial lamellae are incomplete and typically have no central canal.

Composition of the Bone Matrix

Composition of the Bone Matrix • The matrix of bone connective tissue has both organic and inorganic components. • The organic component is osteoid, which is produced by osteoblasts. • Osteoid is composed of both collagen protein plus a semisolid ground substance of proteoglycans (including chondroitin sulfate) and glycoproteins that suspends and supports the collagen fibers. • These organic components give bone tensile strength by resisting stretching and twisting, and contribute to its overall flexibility. • The inorganic portion of the bone matrix is made up of salt crystals that are primarily calcium phosphate, Ca3(PO4)2. • Calcium phosphate and calcium hydroxide interact to form crystals of hydroxyapatite, which is Ca10(PO4)6(OH)2. • The crystals also incorporate other salts (e.g., calcium carbonate) and ions (e.g., sodium, magnesium, sulfate, and fluoride) during the process of calcification. • These crystals deposit around the long axis of collagen fibers in the extracellular matrix. • The crystals harden the matrix and account for the rigidity or relative inflexibility of bone that provide its compressional strength. • The correct proportion of organic and inorganic substances in the matrix of bone allows it to function optimally. • A loss of protein, or the presence of abnormal protein, results in brittle bones; insufficient calcium results in soft bones.

four main steps in intramembranous ossification

It begins when mesenchyme becomes thickened and condensed with a dense supply of blood capillaries, and it continues in the following steps (figure 7.10): • 1 Ossification centers form within thickened regions of mesenchyme beginning at the eighth week of development. Some cells in the thickened, condensed mesenchyme divide, and the committed cells that are formed then differentiate into osteoprogenitor cells. Some osteoprogenitor cells become osteoblasts and begin to secrete osteoid. Multiple ossification centers develop within the thickened mesenchyme as the number of osteoblasts increases. • 2 Osteoid undergoes calcification. Osteoid formation is quickly followed by calcification, as calcium salts are deposited onto the osteoid and then they crystallize (solidify). When calcification entraps osteoblasts within lacunae in the matrix, the entrapped cells become osteocytes. • 3 Woven bone and its surrounding periosteum form. Initially, the newly formed bone connective tissue is immature and not well organized, a type called woven bone, or primary bone. Eventually woven bone is replaced by lamellar bone, or secondary bone (see next). The mesenchyme that still surrounds the woven bone begins to thicken and eventually organizes to form the periosteum. Mesenchymal cells grow and develop to produce additional osteoblasts. Newly formed blood vessels also branch throughout this region. The calcified trabeculae and intertrabecular spaces are composed of spongy bone. • 4 Lamellar bone replaces woven bone, as compact bone and spongy bone form. Lamellar bone replaces the trabeculae of woven bone. On the internal and external surfaces, spaces between the trabeculae are filled and the bone becomes compact bone. Internally, the trabeculae are modified slightly and produce spongy bone. The typical structure of a flat cranial bone is composed of two external layers of compact bone with a layer of spongy bone in between (see figure 7.4).

how parathyroid hormone and calcitriol function together to regulate blood calcium levels

PTH and calcitriol interact with selected major organs as follows: • Bone connective tissue of the skeleton. PTH and calcitriol act synergistically (their combined effect is greater than the sum of their individual effects) to increase the release of calcium from the bone into the blood, by increasing osteoclast activity. • Kidneys. PTH and calcitriol act synergistically to stimulate the kidney to excrete less calcium in the urine (and thus retain more calcium in the blood). This occurs by increasing calcium reabsorption in the tubules in the kidney (see section 24.6). • Small intestine. A function unique to calcitriol is to increase absorption of calcium from the small intestine into the blood. The removal of calcium from bone, the decrease in loss of calcium from the kidney, and increase in calcium absorption from the gastrointestinal tract result in elevating blood calcium and returning it to within the normal homeostatic range. Subsequently, the release of additional PTH is inhibited by negative feedback.

Spongy Bone Microscopic Anatomy

Spongy Bone Microscopic Anatomy • Unlike compact bone, spongy bone contains no osteons (figures 7.7c, 7.8c) • Instead, its structure is an open lattice of narrow rods and plates of bone, called trabeculae. • Bone marrow (when present) fills in between the trabeculae. • When a segment of spongy bone is examined microscopically, you can see parallel lamellae composed of bone matrix. • Between adjacent lamellae are osteocytes resting in lacunae, with numerous canaliculi radiating from the lacunae. • Nutrients reach the osteocytes by diffusion through cytoplasmic processes within the canaliculi that open onto the surfaces of the trabeculae. • Note that the trabeculae often form a meshwork of crisscrossing bars and plates of small bone pieces. • This structure provides great resistance to stresses applied in many directions by distributing the stress throughout the entire framework. • As an analogy, visualize the jungle gym climbing apparatus on a children's playground. • It is capable of supporting the weight of numerous children whether they are distributed throughout its structure or all localized in one area. • This is accomplished because stresses and forces are distributed throughout the structure.

activation of vitamin D to calcitriol

To effectively describe the actions of calcitriol and parathyroid hormone we first describe the enzymatic pathway of activating vitamin D to calcitriol. The three steps are as follows (figure 7.14): • 1 Ultraviolet light converts the precursor molecule in keratinocytes of the skin (7-dehydrocholesterol, a modified cholesterol molecule) to vitamin D3 (cholecalciferol), which is released into the blood. Vitamin D3 also is absorbed from the small intestine into the blood from the diet. • 2 Vitamin D3 circulates throughout the blood. As it passes through the blood vessels of the liver, it is converted by liver enzymes to calcidiol by the addition of a hydroxyl group (—OH). Both steps 1 and 2 occur continuously with limited regulation. • 3 Calcidiol circulates in the blood: As it passes through blood vessels of the kidney, it is converted to calcitriol by kidney enzymes (when another —OH group is added). Calcitriol is the active form of Vitamin D3. The presence of parathyroid hormone increases the rate of this final enzymatic step in the kidney. Thus, greater amounts of calcitriol are formed when PTH is present. Vitamin D in its active form of calcitriol hormone has the unique function of stimulating absorption of calcium ions (Ca2+) from the small intestine into the blood.

how age influences bone structure

• Aging affects bone connective tissue in two ways. • First, the tensile strength of bone decreases due to a reduced rate of protein synthesis by osteoblasts. • Consequently, the relative amount of inorganic minerals in the bone matrix increases (due to decreased matrix protein), and the bones of the skeleton become brittle and susceptible to fracture. • Second, bone loses calcium and other minerals (demineralization). • The bones of the skeleton become thinner and weaker, resulting in insufficient ossification, a condition called osteopenia. • Aging causes all people to become slightly osteopenic. • This reduction in bone mass may begin as early as 35-40 years of age, when osteoblast activity declines, while osteoclast activity continues at previous levels. • Different parts of the skeleton are affected unequally. • Vertebrae, jaw bones, and epiphyses lose large amounts of mass, resulting in reduced height, loss of teeth, and fragile limbs. • Every decade, women lose roughly more of their skeletal mass than do men. • A significant percentage of older women and a smaller proportion of older men suffer from osteoporosis, a condition characterized by reduction in bone mass sufficient to compromise normal function. • In addition, vitamin D and numerous hormones including growth hormone, estrogen, and testosterone decrease with age. • This decrease in hormone levels contributes to reduction in bone mass.

Appositional Growth

• Appositional growth occurs within the periosteum (figure 7.13). • In this process, osteoblasts in the inner cellular layer of the periosteum produce and deposit bone matrix within layers parallel to the surface, called external circumferential lamellae. • These lamellae are analogous to tree rings: As they increase in number, the structure increases in diameter. • Thus, the bone becomes wider as new bone is laid down at its periphery. • As this new bone is being laid down, osteoclasts along the medullary cavity resorb bone matrix, creating an expanding medullary cavity. • The combined effects of bone growth at the periphery and bone resorption within the medullary cavity transform an infant bone into a larger version called an adult bone.

four steps by which fractures heal

• Bone has great mineral strength, but it may break as a result of unusual stress or a sudden impact. • Breaks in bones are called fractures and are classified in several ways. • A stress fracture is a thin break caused by increased physical activity in which the bone experiences repetitive loads (e.g., as seen in some runners). • A pathologic fracture usually occurs in bone that has been weakened by disease. • In a simple fracture, the broken bone does not penetrate the skin, whereas in a compound fracture, one or both ends of the broken bone pierce the overlying skin. • Figure 7.16 shows the different classifications of fractures. • The healing of a simple fracture takes about 2 to 3 months, whereas a compound fracture takes longer to heal. • Fractures heal much more quickly in young children (average healing time, 3 weeks) and become slower to heal as we age. • In the elderly, the normal thinning and weakening of bone increases the incidence of fractures, and some complicated fractures require surgical intervention to heal properly. Bone fracture repair can be described as a series of four steps (figure 7.17): • 1 A fracture hematoma forms. A bone fracture tears blood vessels inside the bone and within the periosteum, causing bleeding. This bleeding results in a fracture hematoma that forms from the clotted blood. • 2 A fibrocartilaginous (soft) callus forms. Regenerated blood capillaries infiltrate the fracture hematoma. First, the fracture hematoma is reorganized into an actively growing connective tissue called a procallus. Fibroblasts within the procallus produce collagen fibers that help connect the broken ends of the bones. Chondroblasts in the newly growing connective tissue form a dense regular connective tissue associated with the cartilage. Eventually, the procallus becomes a fibrocartilaginous (soft) callus (kal′u˘ s; hard skin). The fibrocartilaginous callus stage lasts at least 3 weeks. • 3 A hard (bony) callus forms. Within a week after the injury, osteoprogenitor cells in areas adjacent to the fibrocartilaginous callus become osteoblasts and produce trabeculae of primary bone. The fibrocartilaginous callus is then replaced by this bone, which forms a hard (bony) callus. The trabeculae of the hard callus continue to grow and thicken for several months. • 4 The bone is remodeled. Remodeling is the final phase of fracture repair. The hard callus persists for at least 3 to 4 months, as osteoclasts remove excess bony material from both exterior and interior surfaces. Compact bone replaces primary bone. The fracture usually leaves a slight thickening of the bone (as detected by x-ray); however, in some instances healing occurs with no persistent obvious thickening.

Blood Supply and Innervation of Bone

• Bone is highly vascularized (meaning it is supplied by many blood vessels), especially in regions containing spongy bone (see figure 7.3a). • Blood vessels enter bones from the periosteum. • Typically, only one nutrient artery enters and one nutrient vein exits the bone via a small opening or hole in the bone called a nutrient foramen. • Blood vessels supply nutrients and oxygen required by cells and remove waste products from bone cells. • Nerves that supply bones accompany blood vessels through the nutrient foramen and innervate the bone as well as its periosteum, endosteum, and marrow cavity. • These are mainly sensory nerves that signal injuries of the skeleton.

structure and location of the two types of bone marrow

• Bone marrow is the soft connective tissue of bone that includes red bone marrow and yellow bone marrow ( figure 7.5). • Red bone marrow (myeloid tissue) is hemopoietic (blood cell forming) and contains reticular connective tissue, immature blood cells, and fat. • The locations of red bone marrow differ between children and adults. • In children, red bone marrow is located in the spongy bone of most of the bones of the body as well as the medullary cavity of long bones. • Much of the red bone marrow degenerates as children mature into adults, and the marrow primarily in the medullary cavities of long bones turns into a fatty substance called yellow bone marrow. • As a result, adults have red bone marrow only in selected portions of the axial skeleton, such as the flat bones of the skull, the vertebrae, the ribs, the sternum, and the ossa coxae (hip bone). • Adults also have red bone marrow in the proximal epiphyses of each humerus and femur. • Note that severe anemia—a condition in which erythrocyte (red blood cell) numbers are lower than normal, resulting in insufficient oxygen reaching the cells of the body—may trigger conversion of yellow bone marrow back to red bone marrow, a change that facilitates the production of additional erythrocytes. • (See Clinical View: "Anemia", on page 714.)

major classes of bones as determined by shape

• Bones appear in various shapes and sizes, depending upon their function. The four classes of bone as determined by shape are: o long bones, o short bones, o flat bones, and o irregular bones (figure 7.2).

Bones of the skeleton

• Bones of the skeleton are the primary organs of the skeletal system. • They form the rigid framework of the body and perform other functions described shortly. • Two types of bone connective tissue are present in most of the bones of the body: o compact bone and o spongy bone (see section 5.2d).

general functions of bone

• Bones perform several basic functions: o support and protection, o movement, o hemopoiesis, and o storage of mineral and energy reserves.

Support and Protection

• Bones provide structural support and serve as a framework for the entire body. • Bones also protect many delicate tissues and organs from injury and trauma. • The rib cage protects the heart and lungs; the cranial bones enclose and protect the brain; the vertebrae enclose the spinal cord; and the pelvis cradles urinary and reproductive organs, as well as the terminal end of the gastrointestinal tract.

Movement

• Bones serve as attachment sites for skeletal muscles, other soft tissues, and some organs. • Muscles attached to the bones of the skeleton contract and exert a pull on the skeleton that then functions as a system of levers. • The bones of the skeleton can alter the direction and magnitude of the forces generated by the skeletal muscles. • Potential movements range from powerful contractions needed for running and jumping to delicate and precise movements required to remove a splinter from the finger.

the homeostatic system involving the hormone calcitonin and its effect on blood calcium levels

• Calcitonin is another hormone that aids in regulating blood calcium levels—however, it has a less significant role than either PTH or calcitriol. • Calcitonin is released from the thyroid gland—specifically, from its parafollicular cells in response to high blood calcium levels; it is also secreted in response to stress from exercise. • Although the entire function of calcitonin is unclear, it is known that calcitonin primarily inhibits osteoclast activity. • In addition, calcitonin stimulates the kidneys to increase the loss of calcium in the urine. The result is a reduction in blood calcium levels. The following limitations are observed with calcitonin: • Calcitonin seems to have the greatest effect under conditions where there is the greatest turnover of bone, such as in growing children. • If high doses of calcitonin are administered, blood calcium levels decrease only temporarily. Thus, therapeutic injections of calcitonin cannot provide long-term decrease in blood calcium.

Cartilage

• Cartilage is a semirigid connective tissue that is more flexible than bone. • Recall from section 5.2d that there are three subtypes of cartilage; the two most common subtypes are described below (figure 7.1).

Compact bone

• Compact bone (also called dense or cortical bone) is a relatively dense connective bone tissue that appears white, smooth, and solid. It makes up approximately 80% of the total bone mass.

endochondral ossification of a long bone

• Endochondral ossification begins with a hyaline cartilage model and produces most bones of the skeleton, including those of the upper and lower limbs, the pelvis, the vertebrae, and the ends of the clavicle. • Long bone development in the limb is a good example of this process, which takes place in the following six steps (figure 7.11): • 1 The fetal hyaline cartilage model develops. During the eighth to twelfth week of development, chondroblasts secrete cartilage matrix and a hyaline cartilage model forms. Chondrocytes are trapped within lacunae, and a perichondrium surrounds the cartilage. • 2 Cartilage calcifies, and a periosteal bone collar forms. Within the center of the cartilage model (future diaphysis), chondrocytes start to hypertrophy (enlarge) and resorb (eat away) some of the surrounding cartilage matrix, producing larger holes in the matrix. As these chondrocytes enlarge, the cartilage matrix begins to calcify. Chondrocytes in this region die and disintegrate because nutrients cannot diffuse to them through this calcified matrix. The result is a calcified cartilage shaft with large holes where living chondrocytes had been. As the cartilage in the shaft is calcifying, blood vessels grow toward the cartilage and start to penetrate the perichondrium around the shaft. Stem cells within the perichondrium divide to form osteoblasts. The osteoblasts develop as this supporting connective tissue becomes highly vascularized, and the perichondrium becomes a periosteum. The osteoblasts within the internal layer of the periosteum start secreting a layer of osteoid around the calcified cartilage shaft. The osteoid hardens and forms a periosteal bone collar around this shaft. • 3 The primary ossification center forms in the diaphysis. A growth of capillaries and osteoblasts, called a periosteal bud, extends from the periosteum into the core of the cartilage shaft, invading the spaces where the living chondrocytes had been. The remains of the calcified cartilage serve as a template on which osteoblasts begin to produce osteoid. This region is called the primary ossification center because it is the first major center of bone formation. Bone development extends in both directions toward the epiphyses from the primary ossification center. Healthy bone connective tissue quickly displaces the calcified, degenerating cartilage in the shaft. Most, but not all, primary ossification centers have formed by the twelfth week of development. • 4 Secondary ossification centers form in the epiphyses. The same basic process that formed the primary ossification center occurs later in the epiphyses. Beginning around the time of birth, the hyaline cartilage in the center of each epiphysis calcifies and begins to degenerate. Epiphyseal blood vessels and osteoprogenitor cells enter each epiphysis. Secondary ossification centers form as bone displaces calcified cartilage. Note that not all secondary ossification centers form at birth; some form later in childhood. As the secondary ossification centers form, osteoclasts resorb some bone matrix within the diaphysis, creating a hollow medullary cavity. • 5 Bone replaces almost all cartilage, except the articular cartilage and epiphyseal cartilage. By late bone development, almost all of the hyaline cartilage is displaced by bone. Hyaline cartilage remains as articular cartilage only on the articular surface of each epiphysis and at the epiphyseal plates. • 6 Lengthwise growth continues until the epiphyseal plates ossify and form epiphyseal lines. Lengthwise bone growth continues into puberty until the epiphyseal plate is converted to the epiphyseal line, indicating that the bone has reached its adult length. Depending upon the bone, most epiphyseal plates ossify to become epiphyseal lines between the ages of 10 and 25. (The last epiphyseal plates to ossify are those of the clavicle in the late 20s.)

bone remodeling, and give examples of how it varies in different bones and different portions of the same bone

• Even when adult bone size has been reached, the bone continues to renew and reshape itself throughout a person's lifetime. • This constant, dynamic process of continual addition of new bone tissue (bone deposition) and removal of old bone tissue (bone resorption) is a process called bone remodeling. • This ongoing process occurs at both the periosteal and endosteal surfaces of a bone. • It is estimated that about 20% of the adult human skeleton is replaced yearly. • However, bone remodeling does not occur at the same rate everywhere in the skeleton. • For example, the compact bone in our skeleton is replaced at a slower rate than the spongy bone. • The distalpart of the femur (thigh bone) is replaced every 4 to 6 months, whereas the diaphysis of this bone may not be completely replaced during an individual's lifetime. • Clearly, bone remodeling is dependent upon the coordinated activities of osteoblasts, osteocytes, and osteoclasts. • The relative activities of these cells is influenced by two primary factors: hormones (described in the next section) and mechanical stress to the bone.

Fibrocartilage

• Fibrocartilage is a weight-bearing cartilage that withstands compression. • It forms the intervertebral discs, the pubic symphysis (cartilage between bones of the pelvis), and cartilage pads of the knee joints (menisci).

Flat bones

• Flat bones are so named because they have flat, thin surfaces that may be slightly curved. • They provide extensive surfaces for muscle attachment and protect underlying soft tissues. • Flat bones form the roof of the skull, the scapulae (shoulder blades), the sternum (breastbone), and the ribs.

Glucocorticoids (influence on bone growth and bone remodeling)

• Glucocorticoids are a group of steroid hormones that are released from the adrenal cortex and regulate blood glucose levels. • High amounts increase bone loss and, in children, impairs growth at the epiphyseal plate. • It is because of this relationship that a child's growth is monitored if receiving high doses of glucocorticoids as an anti-inflammatory, such as a treatment for children with severe asthma.

Interstitial growth in the epiphyseal plate

• Growth in bone length occurs specifically within both zone 2 as chondrocytes undergo mitotic cell division, and in zone 3 as chondrocytes hypertrophy. • These activities combine to push the zone of resting cartilage toward the epiphysis. • Note that it is the flexible matrix of hyaline cartilage, and not the hard, calcified matrix of bone, that permits this growth. • Once growth in length has occurred, new bone connective tissue is then produced at the same rate in zone 5. • Thus, growth in length is due to growth in hyaline cartilage connective tissue that is later replaced with bone. • This process is similar to the endochondral ossification process that occurs during bone development. • The epiphyseal plate maintains its thickness during childhood as it is pushed away from the center of the shaft. • At maturity, the rate of epiphyseal cartilage production slows, and the rate of osteoblast activity accelerates. • As a result, the epiphyseal plate continues to narrow until it ultimately disappears, and interstitial growth completely stops. • Eventually, the only remnant of each epiphyseal plate is an internal thin line of compact bone called an epiphyseal line. • The loss of the hyaline cartilage and the appearance of the remnant epiphyseal line signals the end of interstitial growth.

Hemopoiesis

• Hemopoiesis is the process of blood cell production. • It occurs in red bone marrow connective tissue that contains stem cells that form blood cells and platelets. • (The process of hemopoiesis is described in greater detail in section 18.3a.)

Growth hormone (influence on bone growth and bone remodeling)

• Hormones are defined as molecules released from one cell into the blood, and travel throughout the body to affect other cells (see chapter 17). • Certain hormones influence bone composition and growth patterns by altering the rates of chondrocyte, osteoblast, and osteoclast activity (table 7.2). • Growth hormone (aka somatotropin) is produced by the anterior pituitary gland (see section 17.8a). • It affects bone growth by stimulating the liver to form another hormone called insulin-like growth factor (IGF) aka somatomedin. • Both growth hormone and IGF directly stimulate growth of cartilage in the epiphyseal plate.

Hyaline cartilage

• Hyaline cartilage attaches ribs to the sternum (costal cartilage), covers the ends of some bones (articular cartilage), and is the cartilage within growth plates (epiphyseal plates). • Hyaline cartilage also provides a model for the formation of most of the bones in the body.

the structure of hyaline cartilage and the cells in its matrix

• Hyaline cartilage contains a population of cells scattered throughout a glassy-appearing matrix of protein fibers (primarily collagen) embedded within a gel-like ground substance (see section 5.2d). • This ground substance is similar to that of bone in that it includes proteoglycans, such as chondroitin sulfate, but it differs from bone because its inorganic salts do not include calcium. • This makes hyaline cartilageboth resilient and flexible. • Additionally, cartilage also contains a high percentage of water (60% to 70% by weight). • The high water content makes it highly compressible, allowing hyaline cartilage to function as a good shock absorber. • Chondroblasts: • are derived from mesenchymal cells and they produce the cartilage matrix. • Once chondroblasts become encased within the matrix they have produced and secreted, the cells are called chondrocytes and occupy small spaces called lacunae. • These mature cartilage cells maintain the matrix. • Hyaline cartilage— except the articular cartilage— is covered by a dense irregular connective tissue sheet called the perichondrium that helps maintain its shape. • Mature cartilage is avascular (not penetrated by blood vessels) and contains no nerves. • Nutrients and oxygen are supplied to the cartilage by diffusion from blood vessels in the perichondrium. • Several important differences between bone connective tissue and hyaline cartilage connective tissue are summarized in table 7.1.

bones that are produced by intramembranous ossification

• Intramembranous ossification literally means "bone growth within a membrane." • It is so named because the thin layer of mesenchyme in these areas is sometimes referred to as a membrane. • Intramembranous ossification also is called dermal ossification because the mesenchyme that is the source of these bones is in the area of the future dermis. • Recall from section 5.2 that mesenchyme is an embryonic connective tissue that has mesenchymal cells and abundant ground substance. • Intramembranous ossification produces the flat bones of the skull, some of the facial bones (zygomatic bone, maxilla), the mandible (lower jaw), and the central part of the clavicle (collarbone).

Irregular bones

• Irregular bones have elaborate, sometimes complex shapes and do not fit into any of the preceding categories. • The vertebrae; ossa coxae (hip bones); and several bones in the skull, such as the ethmoid, sphenoid, and sutural bones, are examples of irregular bones.

Long bones

• Long bones are greater in length than width. • These bones have an elongated, cylindrical shaft (diaphysis). • This is the most common bone shape. • Long bones are found in the upper limbs (namely, the arm, forearm, palm, and fingers) and lower limbs (thigh, leg, sole of the foot, and toes). • Long bones vary in size. • The small bones in the fingers and toes are long bones, as are the larger tibia and fibula of the lower limb.

Gross Anatomy of a Long Bone

• Long bones are the most common bone shape in the body and thus serve as a useful model of • bone structure (figure 7.3a). • Regions of a Long Bone One of the principal gross features of a long bone is its shaft, which is called the diaphysis. • The elongated, usually cylindrical, diaphysis provides for the leverage and major weight support of a long bone. • Extending inward from the compact bone along the length of the diaphysis are spicules (think spike-like structures) of spongy bone. • The hollow, cylindrical space within the diaphysis is called the medullary (marrow) cavity. • In children, this cavity contains red bone marrow, which later is replaced by yellow bone marrow in adults. • An expanded knobby region called the epiphysis is at each end of a long bone. • A proximal epiphysis is the end of the bone closest to the body trunk, and a distal epiphysis is the end farthest from the trunk. • An epiphysis is composed of an outer thin layer of compact bone and an inner, more extensive region of spongy bone. • Spongy bone within the epiphysis resists stress that is applied from many directions. • Covering the joint surface of an epiphysis is a thin layer of hyaline cartilage called the articular cartilage. • This cartilage helps reduce friction and absorb shock in moveable joints. • The metaphysis is the region in a mature bone sandwiched between the diaphysis and the epiphysis. • This region contains the epiphyseal, or growth, plate in a growing bone. • It is a thin layer of hyaline cartilage that provides for the continued lengthwise growth of the bone. • The remnant of the epiphyseal plate in adults is a thin, defined area of compact bone called the epiphyseal line. • Coverings and Linings of Bone • A tough sheath called periosteum covers the outer surface of the bone except for the areas covered by articular cartilage (figure 7.3a, c). • The periosteum consists of two layers. • The outer fibrous layer of dense irregular connective tissue protects the bone from surrounding structures, anchors blood vessels and nerves to the surface of the bone, and serves as an attachment site for ligaments and tendons. • The inner cellular layer includes osteoprogenitor cells, osteoblasts, and osteoclasts. • The function of these cells is described shortly. • The periosteum is anchored to the bone by numerous collagen fibers called perforating fibers, o Sharpey's fibers, which run perpendicular to the diaphysis. • The endosteum is an incomplete layer of cells that covers all internal surfaces of the bone within the medullary cavity (figure 7.3a, b). • The endosteum, like the periosteum, contains osteoprogenitor cells, osteoblasts, and osteoclasts.

effect of mechanical stress on bone remodeling

• Mechanical stress occurs in the form of weight-bearing movement and exercise, and it is required for normal bone remodeling. • Stress is detected by osteocytes and communicated to osteoblasts. • Osteoblasts increase synthesis of osteoid, and this is followed by deposition of mineral salts. • Bone strength increases over a period of time in response to mechanical stress. • Mechanical stresses that significantly affect bone result from skeletal muscle contraction and gravitational forces. • Typically, the bones of athletes become noticeably thicker as a result of repetitive and stressful exercise. • Weight-bearing activities, such as weight lifting, walking, or running help build and retain bone mass. • Research has shown that regular weight-bearing exercise can increase total bone mass in adolescents and young adults prior to its inevitable reduction later in life. • In fact, research suggests that even 70- and 80-year-olds who perform moderate weight training can increase their bone mass. • In contrast, removal or significant decrease of mechanical stress weakens bone through both reduction of collagen formation and demineralization. • When a person has a fractured bone and wears a cast or is bedridden, the strength of the unstressed bone decreases in the immobilized limb. • While in space, astronauts must exercise so that the lack of gravity won't cause their bones to lose mass.

Ossification

• Ossification, or osteogenesis, refers to the formation and development of bone connective tissue. • Ossification begins in the embryo and continues as the skeleton grows during childhood and adolescence. • By the eighth through twelfth weeks of embryonic development, the skeleton begins forming from either thickened condensations of mesenchyme (intramembranous ossification) or a hyaline cartilage model of bone (endochondral ossification).

Osteoblasts

• Osteoblasts are formed from osteoprogenitor stem cells. • Often, osteoblasts are positioned side by side on bone surfaces. • Active osteoblasts exhibit a somewhat cuboidal shape and have abundant rough endoplasmic reticulum and Golgi apparatus, reflecting the activity of these cells. • Osteoblasts perform the important function of synthesizing and secreting the initial semisolid organic form of bone matrix called osteoid. • Osteoid later calcifies as a result of salt crystal deposition. • As a consequence of this mineral deposition on osteoid, osteoblasts become entrapped within the matrix they produce and secrete, and thereafter they differentiate into osteocytes.

Osteoclasts

• Osteoclasts are large, multinuclear, phagocytic cells. • They are derived from fused bone marrow cells similar to those that produce monocytes (described in section 18.3c). • These cells exhibit a ruffled border where they contact the bone, which increases their surface area exposure to the bone. • An osteoclast is often located within or adjacent to a depression or pit on the bone surface called a resorption lacuna (Howship's lacuna). • Osteoclasts are involved in breaking down bone in an important process called bone resorption (described shortly).

Osteocytes

• Osteocytes are mature bone cells derived from osteoblasts that have lost their bone-forming ability when enveloped by calcified osteoid. • Connections between the original neighboring osteoblasts are maintained as they become osteocytes. • Osteocytes maintain the bone matrix and detect mechanical stress on a bone. • If stress is detected, osteoblasts are signaled, and it may result in the deposition of new bone matrix at the surface.

Osteoprogenitor cells

• Osteoprogenitor cells are stem cells derived from mesenchyme (see section 5.2c). • When they divide through the process of cellular division, another stem cell is produced along with a "committed cell" that matures to become an osteoblast. • As previously described, these stem cells are located in both the periosteum and the endosteum.

the release of parathyroid hormone

• Parathyroid hormone (PTH) is secreted and released by the parathyroid glands (see section 17.10b) in response to reduced blood calcium levels ( figure 7.15). • The final enzymatic step converting calcidiol to calcitriol in the kidney occurs more readily in the presence of PTH.

Serotonin (influence on bone growth and bone remodeling)

• Serotonin was previously discussed in section 1.6. • Researchers have discovered that most bone cells have serotonin receptors, and specifically that when levels of circulating serotonin are too high, osteoprogenitor cells are prevented from differentiating into osteoblasts. • Thus, serotonin appears to play a role in the rate and regulation of normal bone remodeling because it affects osteoblast differentiation. • Further research is ongoing to see if abnormally high levels of serotonin are linked to low bone density disorders. • Three additional hormones—parathyroid hormone, calcitriol, and calcitonin—participate in both regulating bone remodeling and regulating blood calcium levels. • These hormones are discussed in detail in the next section.

Sex hormones - Estrogen / Testosterone (influence on bone growth and bone remodeling)

• Sex hormones (estrogen and testosterone), which begin to be secreted in relatively large amounts at puberty (see section 28.1b), dramatically accelerate bone growth. • Sex hormones increase the rate of both cartilage growth and bone formation within the epiphyseal plate. • Ironically, the appearance of high levels of sex hormones at puberty also signals the beginning of the end for growth at the epiphyseal plate. • This happens because the rate of bone formation occurs at a faster rate than the rate of cartilage growth. • Bone growth eventually overcomes the region of cartilage, replacing all cartilage with bone at the epiphyseal plates.

Short bones

• Short bones have a length nearly equal to their width. • Examples of short bones include the carpals (wrist bones) and tarsals (bones in the foot). • Sesamoid bones, which are small, sesame seed-shaped bones along the tendons of some muscles, are also classified as short bones. • The patella (kneecap) is the largest sesamoid bone.

Gross Anatomy of Other Bone Classes

• Short, flat, and irregular bones differ in their gross anatomic structure from long bones. • The external surface generally is composed of compact bone, the interior is composed entirely of spongy bone, and there is no medullary cavity. • Figure 7.4 shows the compact and spongy bone arrangement in the skull bone. • Observe the roughly parallel compact bone with a layer of internally placed spongy bone. • In a flat bone of the skull, the spongy bone is also called diploë.

Spongy bone

• Spongy bone (also called cancellous or trabecular bone) is located internal to compact bone, appears porous, and makes up approximately 20% of the total bone mass.

Storage of Mineral and Energy Reserves

• Storage of Mineral and Energy Reserves • Most of the body's reserves of the minerals calcium and phosphate are stored within and then released from bone. • Calcium is an essential mineral for such body functions as muscle contraction (see section 10.3), blood clotting (see section 18.4), and release of neurotransmitter from nerve cells (section 12.8d). • Phosphate is a structural component of ATP, nucleotides, and phospholipids (see chapter 2), and is an important component of the plasma membrane (see section 4.2). • When calcium or phosphate is needed by the body, some bone connective tissue is broken down, and the minerals are released into the blood. • In addition, potential energy in the form of lipids is stored in yellow bone marrow in the shafts of some adult bones.

the four types of bone cells and their functions

• The primary component of bone is bone connective tissue, also called osseous connective tissue. • Bone is composed of both cells and extracellular matrix, like all connective tissue. • We now describe the cells and matrix that compose bone connective tissue, how the matrix is formed and resorbed, and then the two microscopic arrangements (compact bone and spongy bone). Four types of cells are found in bone connective tissue: • osteoprogenitor cells, • osteoblasts, • osteocytes, • and osteoclasts (figure 7.6).

Thyroid hormone (influence on bone growth and bone remodeling)

• Thyroid hormone is secreted by the thyroid gland and stimulates bone growth by influencing the basal metabolic rate of bone cells (see section 17.8b). • If maintained in proper balance, growth hormone and thyroid hormone regulate and maintain normal activity at the epiphyseal plates until puberty.

interstitial and appositional growth of cartilage

• We focus on the process of cartilage growth before discussing bone growth because certain types of bone formation and bone growth are dependent upon the growth of hyaline cartilage. • Cartilage development and growth begins during embryologic development. • Cartilage can grow both in length through the process of interstitial growth, or can grow in width by appositional growth (figure 7.9). • Interstitial growth occurs within the internal regions of cartilage through the following series of four steps (figure 7.9a): • 1 Chondrocytes housed within lacunae are stimulated to undergo mitotic cell division. • 2 Following cell division, two cells occupy a single lacuna; they are now called chondroblasts. • 3 As chondroblasts begin to synthesize and secrete new cartilage matrix, they are pushed apart. These cells now reside in their own lacuna and are called chondrocytes. • 4 The cartilage continues to grow in the internal regions as chondrocytes continue to produce more matrix.