© The McGraw-Hill Companies.
As the main constituent of the
adult skeleton, bone tissue supports fleshy structures, protects vital
organs such as those in the cranial and thoracic cavities, and harbors
the bone marrow, where blood cells are formed. Bone also serves as a
reservoir of calcium, phosphate, and other ions that can be released or
stored in a controlled fashion to maintain constant concentrations of
these important ions in body fluids.
In addition, bones form a system of levers that
multiply the forces generated during skeletal muscle
contraction and transform them into bodily movements. This mineralized
tissue therefore confers mechanical and metabolic functions to the
Bone is a specialized connective tissue composed of
calcified intercellular material, the bone matrix,
and three cell types:
Osteocytes (Gr. osteon, bone + kytos,
cell), which are found in cavities (lacunae) between layers
(lamellae) of bone matrix (Figure 8–1)
Osteoblasts (osteon + Gr. blastos,
germ), which synthesize the organic components of the matrix
Osteoclasts (osteon + Gr. klastos,
broken), which are multi-nucleated giant cells involved in the resorption
and remodeling of bone tissue.
Because metabolites are unable to diffuse through the calcified matrix of bone, the exchanges between
osteocytes and blood capillaries depend on communication through the canaliculi
(L. canalis, canal), which are very thin, cylindrical spaces that
perforate the matrix (Figure 8–1).
All bones are lined on both
internal and external surfaces by layers of connective tissue containing
osteogenic cells—endosteum on the internal surface and periosteum
on the external surface.
Because of its hardness, bone cannot be sectioned
with the microtome, and special steps must be taken
to study it histologically. A common technique that permits the
observation of the cells and the organic part of the matrix is based on
the decalcification of bone preserved by standard fixatives. The mineral
is removed by immersion in a solution containing a calcium-chelating
substance such as ethylenediaminetetraacetic acid (EDTA). The decalcified
tissue is then embedded, sectioned, and stained as usual.
Osteoblasts are responsible for
the synthesis of the organic components of bone matrix, consisting of
type I collagen fibers, proteoglycans, and several glycoproteins
including osteonectin. Deposition of the inorganic components of bone
also depends on viable osteoblasts. Osteoblasts are located exclusively
at the surfaces of bone matrix, usually side by side in a layer somewhat
resembling a simple epithelium (Figure 8–2). When they are actively
engaged in matrix synthesis, osteoblasts have a cuboidal to columnar shape
and basophilic cytoplasm. When their synthesizing activity declines, they
flatten and cytoplasmic basophilia is reduced. Osteoblast activity is
stimulated by parathyroid hormone (PTH).
During matrix synthesis,
osteoblasts have the ultrastructure of cells actively synthesizing
proteins for secretion. Osteoblasts are polarized cells: matrix
components are secreted at the cell surface in contact with older bone
matrix, producing a layer of new (but not yet calcified) material called osteoid
between the osteoblast layer and the bone formed earlier (Figure 8–2).
This process of bone appositional growth is completed by subsequent
deposition of calcium salts into the newly formed matrix.
Calcification of the matrix is not completely
understood, but basic aspects of the process are
shown in Figure 8–3. Prominent among the noncollagen proteins secreted by
osteoblasts is the small, vitamin K-dependent polypeptide osteocalcin,
which together with various glycoproteins binds Ca2+ ions and
raises their concentration locally. Osteoblasts also release
membrane-enclosed vesicles rich in alkaline phosphatase and other enzymes
whose activity raises the local concentration of PO4-
ions. With high concentrations of both ions, these matrix vesicles
serve as foci for the formation of hydroxyapatite [Ca10(PO4)6(OH)2]
crystals, the first visible step in calcification. These crystals grow
rapidly by accretion of more mineral and eventually form a confluent mass
of calcified material embedding the collagen fibers and proteoglycans.
Individual osteoblasts are gradually surrounded by
their own secretion and become osteocytes enclosed
singly within spaces called lacunae. In the transition from
osteoblasts to osteocytes the cells extend many long cytoplasmic
processes, which also become surrounded by calcifying matrix. An
osteocyte and its processes occupy each lacuna and the canaliculi
radiating from it (Figures 8–4 and 8–1).
Processes of adjacent cells make contact via gap
junctions, and molecules are passed via these structures from cell to
cell. The exchange via gap junctions can provide
nourishment for a chain of about ten cells. Some molecular exchange
between osteocytes and blood vessels also takes place through the small
amount of extracellular fluid located between osteocytes and the bone
When compared with osteoblasts,
the flat, almond-shaped osteocytes exhibit a significantly reduced RER
and Golgi apparatus and more condensed nuclear chromatin (Figure 8–4a).
These cells are involved in maintaining the bony matrix and their death
is followed by resorption of this matrix.
The fluorescent antibiotic tetracycline
interacts with great affinity with recently deposited mineralized bone
matrix. Based on this interaction, a method was developed to measure the
rate of bone apposition—an important parameter in the
study of bone growth and the diagnosis of bone growth diseases.
Tetracycline is administered twice to patients, with an interval of 5
days between injections. A bone biopsy is then performed, and the
sections are studied by means of fluorescence microscopy. The distance
between the two fluorescent layers is proportional to the rate of bone
apposition. This procedure is of diagnostic importance in such diseases
as osteomalacia, in which mineralization is impaired, and osteitis
fibrosa cystica, in which increased osteoclast activity results in
removal of bone matrix and fibrous degeneration.
Osteoclasts are very large, motile cells with
multiple nuclei (Figure 8–5). The large size and multinucleated condition
of osteoclasts is due to their origin from the fusion
of bone marrow-derived cells. In areas of bone undergoing resorption,
osteoclasts lie within enzymatically etched depressions or crypts in the
matrix known as resorption bays (formerly called Howship
In active osteoclasts, the surface
against the bone matrix is folded into irregular projections, which form
a ruffled border. Formation of the ruffled borders is related to
the activity of osteoclasts. Surrounding the ruffled border is a clear
cytoplasmic zone rich in actin filaments which is the site of adhesion to
the bone matrix. This circumferential adhesion zone creates a
microenvironment between the osteoclast and the matrix in which bone
resorption occurs (Figure 8–5).
Into this subcellular pocket the osteoclast secretes
collagenase and other enzymes and pumps protons,
forming an acidic environment locally for dissolving hydroxyapatite and
promoting the localized digestion of collagen. Osteoclast activity is
controlled by local signaling factors and hormones. Osteoclasts have
receptors for calcitonin, a thyroid hormone, but not for parathyroid
hormone. Osteoblasts activated by PTH produce a cytokine called
osteoclast stimulating factor. Thus, activity of these two cells is
coordinated and both are essential in bone remodeling.
Inorganic material represents about 50% of the dry
weight of bone matrix. Hydroxyapatite is most abundant, but bicarbonate,
citrate, magnesium, potassium, and sodium are also found. Significant
quantities of amorphous (noncrystalline) CaPO4
are also present. The surface ions of hydroxyapatite are hydrated and a
layer of water and ions forms around this crystal. This layer, the hydration
shell, facilitates the exchange of ions between the crystal and the
In the genetic disease
osteopetrosis, which is characterized by dense, heavy bones
("marble bones"), the osteoclasts lack ruffled borders, and
bone resorption is defective.
The organic matter embedded in the calcified matrix
is type I collagen and ground substance, which
contains proteoglycan aggregates and several specific multiadhesive
glycoproteins, including osteonectin. Calcium-binding
glycoproteins, notably osteocalcin, and the phosphatases released in
matrix vesicles by osteoblasts promote calcification of the matrix. Other
tissues containing type I collagen do not contain these glycoproteins or
matrix vesicles and are not normally calcified. Because of its high
collagen content, decalcified bone matrix is usually acidophilic.
The association of minerals with collagen
fibers is responsible for the hardness and resistance of bone tissue.
After a bone is decalcified, its shape is preserved, but it becomes as
flexible as a tendon. Removal of the organic part of the matrix—which is
mainly collagenous—also leaves the bone with its original shape; however,
it becomes fragile, breaking and crumbling easily when handled.
Periosteum & Endosteum
External and internal surfaces of bone are covered
by layers of bone-forming cells and vascularized
connective tissue called periosteum and endosteum.
The periosteum consists
of a dense fibrous outer layer of collagen bundles and fibroblasts
(Figures 8–1 and 8–6). Bundles of periosteal collagen fibers, called perforating(or
Sharpey's) fibers, penetrate the bone matrix, binding the periosteum
to bone. The innermost cellular layer of the periosteum contains
mesenchymal stem cells called osteoprogenitor cells, with the
potential to divide by mitosis and differentiate into osteoblasts. Osteoprogenitor
cells play a prominent role in bone growth and repair.
The large internal marrow cavities of bone are lined
by endosteum (Figures 8–1 and 8-6). Endosteum
is a single very thin layer of connective tissue, containing flattened
osteoprogenitor cells and osteoblasts, which covers the small spicules or
trabeculae of bone that project into these cavities. The endosteum is
therefore considerably thinner than the periosteum.
The principal functions of periosteum and endosteum
are nutrition of osseous tissue and provision of a
continuous supply of new osteoblasts for repair or growth of bone.
Types of Bone
Gross observation of bone
in cross section shows dense areas generally without
cavities—corresponding to compact bone—and areas with numerous
interconnecting cavities—corresponding to cancellous (spongy)
bone (Figure 8–7). Under the microscope, however, both compact
bone and the trabeculae separating the cavities of cancellous bone have
the same basic histologic structure.
In long bones, the bulbous
ends—called epiphyses (Gr. epiphysis, an excrescence)—are
composed of spongy bone covered by a thin layer of compact bone. The
cylindrical part—the diaphysis (Gr. diaphysis, a growing
between)—is almost totally composed of compact bone, with a thin
component of spongy bone on its inner surface around the bone marrow
cavity. Short bones usually have a core of spongy bone surrounded
completely by compact bone. The flat bones that form the calvaria
(skullcap) have two layers of compact bone called plates (tables),
separated by a thicker layer of spongy bone called the diploë.
of bone shows two types: immature primarybone and mature secondarybone
Primary Bone Tissue
Primary bone is the first bone tissue to appear in
embryonic development and in fracture repair. It is characterized by
random disposition of fine collagen fibers and is
therefore often called woven bone (Figure 8–8). Primary bone
tissue is usually temporary and is replaced in adults by secondary bone
tissue except in a very few places in the body, eg, near the sutures of
the calvaria, in tooth sockets, and in the insertions of some tendons.
In addition to the irregular array of collagen
fibers, other characteristics of primary bone tissue are a lower mineral
content (it is more easily penetrated by x-rays) and a higher proportion
of osteocytes than that in secondary bones.
Secondary Bone Tissue
Secondary bone tissue is the type usually found in
adults. It characteristically shows multiple layers of calcified matrix
(each 3–7 m thick) and is
often referred to as lamellar bone. The lamellae are quite
organized, either parallel to each other or concentrically around a
vascular canal. Each complex of concentric bony lamellae surrounding a
small canal containing blood vessels, nerves, and loose connective tissue
is called an osteon (formerly known as an haversian system)
(Figures 8–1 and 8–9). Lacunae with osteocytes are found between the
lamellae, interconnected by canaliculi which allow all cells to be in
contact with the source of nutrients and oxygen in the osteonic canal
(Figure 8–9). The outer boundary of each osteon is a more collagen-rich
layer called the cement line.
In each lamella, type I collagen
fibers are aligned in parallel and follow a helical course. The pitch of
the helix is, however, different for different lamellae, so that at any
given point, fibers from adjacent lamellae intersect at approximately
right angles (Figure 8–1). The specific organization of collagen fibers
in successive lamellae of each osteon is highly important for the great
strength of secondary bone.
In compact bone (eg, the diaphysis of long bones)
besides forming osteons, the lamellae also exhibit a
typical organization consisting of multiple external circumferential
lamellae (Figure 8–1) and often some inner circumferential
lamellae. Inner circumferential lamellae are located around the
marrow cavity and external circumferential lamellae are located
immediately beneath the periosteum.
Each osteon is a long, often bifurcated cylinder
generally parallel to the long axis of the diaphysis. It consists of a
central canal surrounded by 4–10 concentric lamellae. Each
endosteum-lined canal contains blood vessels, nerves,
and loose connective tissue. The central canals communicate with the
marrow cavity and the periosteum and with one another through transverse
or oblique perforating canals (formerly known as Volkmann canals)
(Figures 8–1 and 8–10). The transverse canals do not have concentric
lamellae; instead, they perforate the lamellae. All osteonic and
perforating canals in bone tissue come into existence when matrix is laid
down around preexisting blood vessels.
Among the osteons between the
two circumferential systems are numerous irregularly shaped groups of
parallel lamellae called interstitial lamellae. These structures
are lamellae remaining from osteons partially destroyed by osteoclasts
during growth and remodeling of bone (Figure 8–10).
Bone remodeling is
continuous throughout life and involves a combination of bone synthesis
and removal. In compact bone, remodeling resorbs parts of old osteons and
produces new ones. Resorption involves the actions of osteoclasts, often
working in groups to remove old bone in tunnel-like cavities having the
approximate diameter of new osteons. Such tunnels are quickly invaded by
many osteoprogenitor cells and sprouting loops of blood capillaries, both
derived from the endosteum or periosteum. Osteoblasts develop, line the
wall of the tunnels, and begin to secrete osteoid in a cyclic manner,
forming concentric lamellae of bone with trapped osteocytes (Figure
8–11). In healthy adults 5–10% of the bone turns over annually.
Variations in the remodeling activity produce great
variability in the sizes of osteons, osteonic canals, and interstitial
lamellae. As osteons form by successive deposition of
lamellae by osteoblasts, moving inward from the periphery, younger
osteons usually have larger canals. In mature osteons the most recently
formed lamella is the one closest to the central canal.
Bone can be formed initially by either of two ways:
Intramembranous ossification, in which
osteoblasts differentiate directly from mesenchyme and begin secreting
Endochondral ossification, in which the
matrix of preexisting hyaline cartilage is eroded and replaced by
osteoblasts producing osteoid.
In both processes, the bone tissue that appears
first is primary or woven. Primary bone is a temporary and is soon
replaced by the definitive secondary lamellar bone. During bone growth,
areas of primary bone, areas of resorption, and areas
of secondary bone all appear side by side.
Intramembranous ossification, by which most flat
bones are produced, is so called because it takes place within
condensations of embryonic mesenchymal tissue. The
frontal and parietal bones of the skull—as well as parts of the occipital
and temporal bones and the mandible and maxilla—are formed by
intramembranous ossification. The process is summarized in Figure 8–12.
In the mesenchymal condensation
layer or "membrane," the starting point for bone formation is
called an ossification center. The process begins when groups of
mesenchymal cells differentiate into osteoblasts. Osteoblasts produce
osteoid matrix and calcification follows, resulting in the encapsulation
of some osteoblasts, which then become osteocytes. These islands of
developing bone form walls that delineate elongated cavities containing
capillaries, bone marrow cells, and undifferentiated cells. Several such
groups arise almost simultaneously at the ossification center, and their
fusion between the walls gives the bone a spongy appearance. The
connective tissue that remains among the bone walls is penetrated by
growing blood vessels and additional undifferentiated mesenchymal cells,
giving rise to the bone marrow. The ossification centers of a bone grow
radially and finally fuse together, replacing the original connective
tissue (Figures 8–12 and 8–13).
In cranial flat bones there is a marked predominance
of bone formation over bone resorption at both the internal and external
surfaces. Thus, two layers of compact bone (internal and external plates)
arise, while the central portion (diploë) maintains
its spongy nature. The fontanelles or "soft spots" on the heads
of newborn infants are areas in the skull that correspond to parts of the
connective tissue that are not yet ossified. The portions of the connective
tissue layer that do not undergo ossification give rise to the endosteum
and the periosteum of the new bone.
Endochondral (Gr. endon,
within, + chondros, cartilage) ossification takes place within a
piece of hyaline cartilage whose shape resembles a small version, or
model, of the bone to be formed. This type of ossification is principally
responsible for the formation of short and long bones.
Endochondral ossification of a long bone consists of
the sequence of events shown schematically in Figure
8–14. Initially, the first bone tissue appears as a collar surrounding
the diaphysis of the cartilage model. This bone collar is produced
by local osteoblast activity within the surrounding perichondrium. The
collar now impedes diffusion of oxygen and nutrients into the underlying
cartilage, promoting degenerative changes there. The chondrocytes begin
to produce alkaline phosphatase and swell up (hypertrophy), enlarging
their lacunae. These changes both compress the matrix into narrower trabeculae
and lead to calcification in these structures. Death of the chondrocytes
results in a porous three-dimensional structure formed by the remnants of
the calcified cartilage matrix (Figure 8–15). Blood vessels from the
former perichondrium now the periosteum penetrate through the bone collar
previously perforated by osteoclasts, bringing osteoprogenitor cells to
the porous central region. Next, osteoblasts adhere to the calcified
cartilage matrix and produce continuous layers of primary bone that
surround the cartilaginous matrix remnants. At this stage, the calcified
cartilage appears basophilic, and the primary bone is eosinophilic
This process in the diaphysis
forms the primary ossification center (Figure 8–14). Secondary
ossification centers appear slightly later at the epiphyses of the
cartilage model and develop in a similar manner. During their expansion
and remodeling, the primary and secondary ossification centers produce
cavities that are gradually filled with bone marrow.
In the secondary ossification centers, cartilage
remains in two regions: the articular cartilage
(Figure 8–14), which persists throughout adult life and does not
contribute to bone growth in length, and the epiphyseal cartilage
(also called epiphyseal plate or growth plate), which connects
each epiphysis to the diaphysis (Figures 8–16 and 8–17). The epiphyseal
cartilage is responsible for the growth in length of the bone and
disappears in adults, which is why bone growth ceases in adulthood.
Elimination of the epiphyseal plates ("epiphyseal closure")
occurs at different times with different bones and is complete in all
bones by about age twenty. In forensics or through X-ray examination of
the growing skeleton, it is possible to determine the "bone
age" of a young person, noting which epiphyses are open and which
are closed. Once the epiphyses have closed, growth in length of bones
becomes impossible, although bone widening may still occur.
A plate of epiphyseal cartilage is divided into five
zones (Figure 8–16), starting from the epiphyseal side of cartilage:
zone consists of hyaline cartilage with typical chondrocytes.
In the proliferative zone, chondrocytes begin to divide
rapidly and form columns of stacked cells parallel to the long axis of
cartilage zone contains swollen chondrocytes whose cytoplasm has
accumulated glycogen. Hypertrophy compresses the matrix into thin septa
between the chondrocytes.
In the calcified cartilage zone, loss of the
chondrocytes by apoptosis is accompanied by calcification of the septa of
cartilage matrix by the formation of hydroxyapatite crystals (Figure
In the ossification zone, bone tissue first appears.
Capillaries and osteoprogenitor cells originating from the periosteum
invade the cavities left by the chondrocytes. Many of these cavities will
be merged and become the marrow cavity. The osteoprogenitor cells form
osteoblasts, which settle in a discontinuous layer over the septa of
calcified cartilage matrix. The osteoblasts deposit osteoid over the
spicules of calcified cartilage matrix, forming woven bone (Figure 8–17).
In summary, growth in length of a long bone occurs
by proliferation of chondrocytes in the epiphyseal
plate adjacent to the epiphysis. At the same time, chondrocytes in the
diaphyseal side of the plate hypertrophy, their matrix becomes calcified,
and the cells die. Osteoblasts lay down a layer of primary bone on the
calcified cartilage matrix. Because the rates of these two opposing
events (proliferation and destruction) are approximately equal, the
epiphyseal plate does not change thickness. Instead, it is displaced away
from the middle of the diaphysis, resulting in growth in length of the
Bone Growth, Remodeling, &
Bone growth is generally associated with partial
resorption of preformed tissue and the simultaneous laying down of new
bone (exceeding the rate of bone loss). This process
permits the shape of the bone to be maintained as it grows. The rate of
bone remodeling (bone turnover) is very active in young children,
where it can be 200 times faster than that in adults. Bone remodeling in
adults is a dynamic physiologic process that occurs simultaneously in
multiple locations of the skeleton and is not always related to bone
Despite its hardness, the constant remodeling makes
bone very plastic and capable of internal structural changes according to
the various stresses to which it is subjected. A
well-known example of bone plasticity is the ability of the positions of
teeth in the jawbone to be modified by the lateral pressures produced by
orthodontic appliances. Bone is formed on the side where traction is
applied and is resorbed on the opposite side where pressure is exerted.
In this way, teeth are moved within the jaw while the bone is being
Cranial bones grow mainly because of the formation
of bone tissue by the periosteum between the sutures
and on the external bone surface. At the same time, resorption takes
place on the internal surface. The plasticity of bone allows it to
respond to the growth of the brain and form a skull of adequate size. The
skull will be small if the brain does not develop completely and will be
larger than normal in a person suffering from hydrocephalus, a disorder
characterized by abnormal accumulation of spinal fluid and dilatation of
the cerebral ventricles.
Because it contains osteoprogenitor stem cells throughout the endosteum and periosteum and has an extensive
blood supply, bone has an excellent capacity for repair and regeneration.
Bone fractures and other damage are repaired efficiently using cells and
processes already active in bone remodeling. Surgically created gaps in
bone can be filled with new bone, especially when periosteal tissue
When a bone is fractured, blood vessels
are disrupted and bone cells adjoining the fracture die. The damaged
blood vessels produce a localized hemorrhage and form
a blood clot.
Soon the blood clot is removed by
macrophages and the adjacent matrix of bone is resorbed by osteoclasts.
The periosteum and the endosteum at the site of the fracture respond with
intense proliferation producing a soft callus of
fibrocartilage-like tissue that surrounds the fracture and covers the
extremities of the fractured bone (Figure 8–18).
Primary bone is then formed by a
combination of endochondral and intramembranous ossification. Further
repair produces irregularly formed trabeculae of
primary bone that temporarily unite the extremities of the fractured
bone, forming a hard bone callus (Figure 8–18).
Stresses imposed on the bone during repair
and during the patient's gradual return to activity serve to remodel the bone callus. The primary bone of the callus is
gradually resorbed and replaced by secondary bone, remodeling and
restoring the original bone structure. Unlike other connective tissues,
bone tissue heals without forming a scar.
Metabolic Role of Bone
Calcium ions are required for the activity of many
enzymes and other proteins mediating cell adhesion,
cytoskeletal movements, exocytosis, membrane permeability, and other
functions in cells throughout the body. The skeleton serves as the
calcium reservoir and contains 99% of the body's total calcium in
crystals of hydroxyapatite. The concentration of calcium in the blood and
tissues is generally quite stable because of a continuous interchange
between blood calcium and bone calcium.
The principal mechanism for raising blood calcium
levels is the mobilization of ions from hydroxyapatite
crystals to interstitial fluid. This takes place mainly in cancellous
bone. The younger, more lightly calcified lamellae that exist even in
adult bone (because of continuous remodeling) receive and lose calcium
more readily. These lamellae are more important for the maintenance of
calcium concentration in the blood than are the older, more densely
calcified lamellae, whose role is mainly that of support and protection.
The action of two key hormones on cells in bone
regulates the process of calcium mobilization from
hydroxyapatite. Parathyroid hormone (PTH) from the parathyroid
glands raises low blood calcium levels. The principal target cells of
this polypeptide are osteoblasts, which stop production of osteoid and
matrix vesicles and instead secrete a paracrine protein, osteoclast
stimulating factor. This factor promotes osteoclastic resorption of the
bone matrix, liberating calcium. Osteoclast activity is inhibited by
another hormone, calcitonin, which is synthesized by the
parafollicular cells of the thyroid gland. This slows matrix resorption
and thereby gradually lowers blood calcium levels.
Because the concentration of calcium in
tissues and blood must be kept constant, nutritional deficiency of
calcium results in decalcification of bones. Severely
decalcified bones are more likely to fracture.
Decalcification of bone may also be caused
by excessive production of PTH (hyperparathyroidism), which can cause
increased osteoclastic activity, intense resorption of bone, elevation of
blood Ca2+ and PO3– 4
levels, and abnormal deposits of calcium in the kidneys and arterial
The opposite occurs in osteopetrosis
(L. petra, stone), a disease caused by defective osteoclast function that
results in overgrowth, thickening, and hardening of bones. This process
can obliterate the bone marrow cavities, depressing blood cell formation
and causing anemia and the loss of white blood cells.
Nutritional Deficiencies and Bone
growth, bone is sensitive to nutritional factors. Calcium deficiency,
which leads to incomplete calcification of the organic bone matrix, can
be due either to a lack of calcium in the diet or a failure to produce
the steroid prohormone vitamin D, which is important for the absorption
of Ca2+ and> PO3–4 by the small
Calcium deficiency in children causes rickets, a disease in which the bone matrix does
not calcify normally and the epiphyseal plate becomes distorted by the
normal strains of body weight and muscular activity. Ossification
processes at this level are consequently hindered, and the bones not only
grow more slowly but also become deformed.
Calcium deficiency in adults gives rise to
osteomalacia (osteon + Gr. malakia,
softness), which is characterized by deficient calcification of recently
formed bone and partial decalcification of already calcified matrix.
Osteomalacia should not be confused with osteoporosis. In
osteomalacia, there is a decrease in the amount of calcium per unit of
bone matrix. Osteoporosis, frequently found in immobilized patients and
in postmenopausal women, is an imbalance in skeletal turnover so that
bone resorption exceeds bone formation.
Hormones Acting on Bone Tissue
In addition to PTH and calcitonin, several other hormones act on bone. The anterior lobe of
the pituitary synthesizes growth hormone (GH or somatotropin), which
stimulates the liver to produce insulin-like growth factor-1 (IGF-1 or
somatomedin). IGF has an overall growth effect, especially on the
epiphyseal cartilage. Consequently, lack of growth hormone during the
growing years causes pituitary dwarfism; an excess of growth
hormone causes excessive growth of the long bones, resulting in gigantism.
Adult bones cannot increase in length even with excess IGF because they
lack epiphyseal cartilage, but they do increase in width by periosteal
growth. In adults, an increase in GH causes acromegaly, a disease
in which the bones—mainly the long ones—become very thick.
The sex hormones, both male (androgens) and female (estrogens), have a complex effect
on bones and are, in a general way, stimulators of bone formation. They
influence the time of appearance and development of ossification centers
and accelerate the closure of epiphyses.
directly from bone cells is fairly uncommon (0.5% of all cancer deaths)
but a form called osteosarcoma can arise in osteoblasts. The
skeleton is often the site of metastases from tumors originating from
malignancies in other organs, most commonly from breast, lung, prostate,
kidney, and thyroid tumors.
Joints are regions where bones are capped and
surrounded by connective tissues that firmly hold the bones together and
determine the type and degree of movement between
them. Joints may be classified as diarthroses, which permit free
bone movement, and synarthroses (Gr. syn, together, + arthrosis,
articulation), in which very limited or no movement occurs. There are
three types of synarthroses, based on the type of tissue uniting the bone
Synostoses, in which bones are united by bone
tissue and no movement takes place. In older adults, synostoses unite the
skull bones, which, in children and young adults, are united only by
dense connective tissue
Synchondroses, in which the bones are joined by
hyaline cartilage. The epiphyseal plates of growing bones are one example
and in adults a synchondrosis unites the first rib to the sternum, with
Syndesmoses, in which bones are joined by an
interosseous ligament of dense connective tissue or fibrocartilage (eg,
the pubic symphysis, Figure 7–1), again with very limited movement.
Diarthroses (Figure 8–19) are joints that generally
unite long bones and have great mobility, such as the elbow and knee joints. In a diarthrosis, ligaments and a
capsule of dense connective tissue maintain proper alignment of the
bones. The capsule encloses a sealed joint cavity that contains synovial
fluid, a colorless, transparent, viscous fluid. The joint cavity is
not lined by epithelium, but by a specialized connective tissue called
the synovial membrane which extends folds and villi into the
cavity and secretes the lubricant synovial fluid. Synovial fluid is
derived from blood plasma, but with a high concentration of hyaluronic
acid produced by cells of the synovial membrane.
The synovial membrane or layer
may have prominent regions with various types of connective tissue
(areolar, fibrous, or adipose) in different diarthrotic joints. At the
surface contacting the synovial fluid the tissue is usually
well-vascularized, with many porous (fenestrated) capillaries, and
contains two specialized cells (synoviocytes) with distinctly different
functions and origins (Figure 8–20). Rounded synoviocytes in contact with
the synovial cavity are phagocytic and remove wear-and-tear debris from
the synovial fluid. Among the capillaries are many more fibroblastic
synoviocytes specialized to produce the long, nonsulfated
glycosaminoglycan (GAG) hyaluronic acid and secrete other components of
ground substance. These GAGs along with plasma from the capillaries leave
the synovial membrane, oozing into the synovial fluid. This viscous,
gel-like fluid lubricates the joint, reducing friction on all internal
surfaces, and supplies nutrients and oxygen to the articular cartilage.
The collagen fibers of the
hyaline articular cartilage are disposed as arches with their tops at the
exposed surface, which unlike most cartilage is not covered by
perichondrium (Figure 8–21). This arrangement of collagen helps to
distribute more evenly the forces generated by pressure on joints. The
resilient articular cartilage is also an efficient absorber of the
intermittent mechanical pressures to which many joints are subjected.
A similar mechanism is seen in intervertebral
disks (Figure 8–22) which are thick disks of fibrocartilage between
the articular surfaces of successive bony vertebrae. The annulus
fibrosus of each disk has an external layer of dense connective
tissue, but is mainly composed of overlapping laminae of fibrocartilage
in which collagen bundles are orthogonally arranged in adjacent layers.
The multiple lamellae, with the 90-degree registration of type I collagen
fibers in adjacent layers, provide the disk with unusual resilience that
enables it to withstand the pressures generated by the impinging
The nucleus pulposus is
situated in the center of the annulus fibrosus. It may contain a few
scattered cells derived from the embryonic notochord, but is largely composed
of viscous, gel-like matrix rich in hyaluronic acid and fibers of type II
collagen. The nucleus pulposus is large in children, but gradually
becomes smaller with age and is partially replaced by fibrocartilage. The
nucleus pulposus allows each intervertebral disk to function as a shock
absorber within the spinal column.
Rupture of the annulus fibrosus, which
most frequently occurs in the posterior region where there are fewer
collagen bundles, results in expulsion of the nucleus
pulposus and a concomitant flattening of the disk. As a consequence, the
disk frequently dislocates or slips from its position between the
vertebrae. If it moves toward the spinal cord, it can compress the nerves
and result in severe pain and neurologic disturbances. The pain
accompanying a slipped disk may be perceived in areas innervated by the
compressed nerve fibers—usually the lower lumbar region.