Bone Tissue and Homeostasis
,Bone tissue is a complex and dynamic living tissue. It continually
engages in a process called bone remodeling—the building of new bone
tissue and breaking down of old bone tissue. In the early days of space
exploration, young, healthy men in prime physical shape returned from
their space flights only to alarm their physicians. Physical examinations
of the astronauts revealed that they had lost up to 20% of their total bone
density during their extended stay in space. The zero-gravity (weightless)
environment of space, coupled with the fact that the astronauts traveled
in small capsules that greatly limited their movement for extended
periods of time, placed minimal strain on their bones. In contrast, athletes
subject their bones to great forces, which place significant strain on the
bone tissue. Accomplished athletes show an increase in overall bone
density. How is bone capable of changing in response to the diff erent
mechanical demands placed on it? Why do high activity levels that strain
bone tissue greatly improve bone health? This chapter surveys the various
components of bones to help you understand how bones form, how they
age, and how exercise aff ects their density and strength.
Functions of Bone and
the Skeletal System
,A bone is an organ made up of several diff erent tissues working
together: bone (osseous) tissue, cartilage, dense connective tissue,
epithelium, adipose tissue, and nervous tissue. The entire framework
of bones and their cartilages constitute the skeletal system. The study
of bone structure and the treatment of bone disorders is referred to as
osteology (os-tē-OL-o-jē; osteo- = bone; -logy = study of).
The skeletal system performs several basic functions:
1. Support. The skeleton serves as the structural framework for the
body by supporting soft tissues and providing attachment points
for the tendons of most skeletal muscles.
2. Protection. The skeleton protects the most important internal
organs from injury. For example, cranial bones protect the brain,
and the rib cage protects the heart and lungs.
3. Assistance in movement. Most skeletal muscles attach to bones;
when they contract, they pull on bones to produce movement. This
function is discussed in detail in Chapter 10.
4. Mineral homeostasis (storage and release). Bone tissue makes
up about 18% of the weight of the human body. It stores several
minerals, especially calcium and phosphorus, which contribute to
the strength of bone. Bone tissue stores about 99% of the body’s
calcium. On demand, bone releases minerals into the blood to
maintain critical mineral balances (homeostasis) and to distribute
the minerals to other parts of the body.
5. Blood cell production. Within certain bones, a connective tissue
called red bone marrow produces red blood cells, white blood
cells, and platelets, a process called hemopoiesis (hēm-ō-poy-ē-sis;
hemo- = blood; -poiesis = making). Red bone marrow consists of
developing blood cells, adipocytes, fibroblasts, and macrophages
within a network of reticular fibers. It is present in developing bones
of the fetus and in some adult bones, such as the hip (pelvic) bones,
ribs, sternum (breastbone), vertebrae (backbones), skull, and ends
of the bones of the humerus (arm bone) and femur (thigh bone). In
a newborn, all bone marrow is red and is involved in hemopoiesis.
With increasing age, much of the bone marrow changes from red to
yellow. Blood cell production is considered in detail in Section 19.2.
6. Triglyceride storage. Yellow bone marrow consists mainly of adi-
pose cells, which store triglycerides. The stored triglycerides are a
potential chemical energy reserve.
Structure of Bone
OBJECTIVE
• Describe the structure and functions of each part of a long
bone.
We will now examine the structure of bone at the macroscopic level.
Macroscopic bone structure may be analyzed by considering the
parts of a long bone, such as the humerus (the arm bone) shown in
Figure 6.1a. A long bone is one that has greater length than width.
A typical long bone consists of the following parts:
1. The diaphysis (dī-AF-i-sis = growing between) is the bone’s shaft
or body—the long, cylindrical, main portion of the bone.
2. The epiphyses (e-PIF-i-sēz = growing over; singular is epiphysis)
are the proximal and distal ends of the bone.
3. The metaphyses (me-TAF-i-sēz; meta- = between; singular is
metaphysis) are the regions between the diaphysis and the epi-
physes. In a growing bone, each metaphysis contains an epiphy-
seal (growth) plate (ep′-i-FIZ-ē-al), a layer of hyaline cartilage that
allows the diaphysis of the bone to grow in length (described later
in the chapter). When a bone ceases to grow in length at about
ages 14–24, the cartilage in the epiphyseal plate is replaced by
bone; the resulting bony structure is known as the epiphyseal line.
4. The articular cartilage is a thin layer of hyaline cartilage covering
the part of the epiphysis where the bone forms an articulation (joint)
with another bone. Articular cartilage reduces friction and absorbs
shock at freely movable joints. Because articular cartilage lacks a
perichondrium and lacks blood vessels, repair of damage is limited.
5. The periosteum (per-ē-OS-tē-um; peri- = around) is a tough con-
nective tissue sheath and its associated blood supply that surrounds
the bone surface wherever it is not covered by articular cartilage. It is
composed of an outer fibrous layer of dense irregular connective tis-
sue and an inner osteogenic layer that consists of cells. Some of the
cells enable bone to grow in thickness, but not in length. The perios-
teum also protects the bone, assists in fracture repair, helps nourish
bone tissue, and serves as an attachment point for ligaments and
tendons. The periosteum is attached to the underlying bone by per-
forating fibers or Sharpey’s fibers, thick bundles of collagen that
extend from the periosteum into the bone extracellular matrix.
6. The medullary cavity (MED-ul-er-ē; medulla- = marrow, pith), or
marrow cavity, is a hollow, cylindrical space within the diaphysis that
contains fatty yellow bone marrow and numerous blood vessels in
adults. This cavity minimizes the weight of the bone by reducing the
dense bony material where it is least needed. The long bones’ tubu-
lar design provides maximum strength with minimum weight.
Histology of Bone Tissue
OBJECTIVES
،
• Explain why bone tissue is classified as a connective tissue.
• Describe the cellular composition of bone tissue and the
functions of each type of cell.
• Compare the structural and functional diff erences between
compact and spongy bone tissue.
We will now examine the structure of bone at the microscopic level.
Like other connective tissues, bone, or osseous tissue (OS-ē-us), con-
tains an abundant extracellular matrix that surrounds widely sepa-
rated cells. The extracellular matrix is about 15% water, 30% collagen
fibers, and 55% crystallized mineral salts. The most abundant mineral
salt is calcium phosphate [Ca3(PO4)2]. It combines with another min-
eral salt, calcium hydroxide [Ca(OH)2], to form crystals of hydroxyapa-
tite [Ca10(PO4)6(OH)2] (hī-drok-sē-AP-a-tīt). As the crystals form, they
combine with still other mineral salts, such as calcium carbonate
(CaCO3), and ions such as magnesium, fluoride, potassium, and sul-
fate. As these mineral salts are deposited in the framework formed by
the collagen fibers of the extracellular matrix, they crystallize and the
tissue hardens. This process, called calcification (kal′-si-fi-KA-
-shun), is
initiated by bone-building cells called osteoblasts (described shortly).
It was once thought that calcification simply occurred when
enough mineral salts were present to form crystals. We now know
that the process requires the presence of collagen fibers. Mineral salts
first begin to crystallize in the microscopic spaces between collagen
fibers. Aft er the spaces are filled, mineral crystals accumulate around
the collagen fibers. The combination of crystallized salts and collagen
fibers is responsible for the characteristics of bone.
Although a bone’s hardness depends on the crystallized inorganic
mineral salts, a bone’s flexibility depends on its collagen fibers. Like
reinforcing metal rods in concrete, collagen fibers and other organic
molecules provide tensile strength, resistance to being stretched or
torn apart. Soaking a bone in an acidic solution, such as vinegar,
dissolves its mineral salts, causing the bone to become rubbery and
flexible. As you will see shortly, when the need for particular minerals
arises or as part of bone formation or breakdown, bone cells called
osteoclasts secrete enzymes and acids that break down both the min-
eral salts and the collagen fibers of the extracellular matrix of bone.
Four types of cells are present in bone tissue: osteoprogenitor
cells, osteoblasts, osteocytes, and osteoclasts (Figure 6.2).
1. Osteoprogenitor cells (os′-tē-ō-prō-JEN-i-tor; -genic = producing)
are unspecialized bone stem cells derived from mesenchyme, the
tissue from which almost all connective tissues are formed. They
are the only bone cells to undergo cell division; the resulting cells
develop into osteoblasts. Osteoprogenitor cells are found along
the inner portion of the periosteum, in the endosteum, and in the
canals within bone that contain blood vessels.
2. Osteoblasts (OS-tē-ō-blasts′; -blasts = buds or sprouts) are
bone-building cells. They synthesize and secrete collagen fibers and
other organic components needed to build the extracellular matrix
of bone tissue, and they initiate calcification (described shortly).
As osteoblasts surround themselves with extracellular matrix, they
become trapped in their secretions and become osteocytes. (Note:
The ending -blast in the name of a bone cell or any other connective
tissue cell means that the cell secretes extracellular matrix.)
3. Osteocytes (OS-tē-ō-sīts′; -cytes = cells), mature bone cells, are the
main cells in bone tissue and maintain its daily metabolism, such
as the exchange of nutrients and wastes with the blood. Like osteo-
blasts, osteocytes do not undergo cell division. (Note: The ending
-cyte in the name of a bone cell or any other tissue cell means that
the cell maintains and monitors the tissue.)
4. Osteoclasts (OS-tē-ō-klasts′; -clast = break) are huge cells derived
from the fusion of as many as 50 monocytes (a type of white blood
cell) and are concentrated in the endosteum. On the side of the cell
that faces the bone surface, the osteoclast’s plasma membrane is
deeply folded into a ruffled border. Here the cell releases powerful lys-
osomal enzymes and acids that digest the protein and mineral com-
ponents of the underlying extracellular bone matrix. This breakdown
of bone extracellular matrix, termed bone resorption (rē-SORP-
shun), is part of the normal development, maintenance, and repair of
bone. (Note: The ending -clast means that the cell breaks down extra-
cellular matrix.) As you will see later, in response to certain hormones,
osteoclasts help regulate blood calcium level (see Section 6.7). They
are also target cells for drug therapy used to treat osteoporosis (see
Disorders: Homeostatic Imbalances at the end of this chapter).
You may find it convenient to use an aid called a mnemonic
device (ne-MON-ik = memory) to learn new or unfamiliar informa-
tion. One such mnemonic that will help you remember the diff erence
between the function of osteoblasts and osteoclasts is as follows:
osteoBlasts Build bone, while osteoClasts Carve out bone.
Bone is not completely solid but has many small spaces between
its cells and extracellular matrix components. Some spaces serve as
channels for blood vessels that supply bone cells with nutrients.
Other spaces act as storage areas for red bone marrow. Depending on
the size and distribution of the spaces, the regions of a bone may be
categorized as compact or spongy (see Figure 6.1). Overall, about
80% of the skeleton is compact bone and 20% is spongy bone.
Compact Bone Tissue
,
Compact bone tissue contains few spaces (Figure 6.3a) and is the
strongest form of bone tissue. It is found beneath the periosteum of
all bones and makes up the bulk of the diaphyses of long bones. Com-
pact bone tissue provides protection and support and resists the
stresses produced by weight and movement.
Compact bone tissue is composed of repeating structural units
called osteons, or haversian systems (ha-VER-shan). Each osteon con-
sists of concentric lamellae arranged around an osteonic (haversian
or central) canal. Resembling the growth rings of a tree, the concen-
tric lamellae (la-MEL-ē) are circular plates of mineralized extracellu-
lar matrix of increasing diameter, surrounding a small network of
blood vessels and nerves located in the central canal (Figure 6.3a).
These tubelike units of bone generally form a series of parallel cylin-
ders that, in long bones, tend to run parallel to the long axis of the
bone. Between the concentric lamellae are small spaces called lacu-
nae (la-KOO-nē = little lakes; singular is lacuna), which contain oste-
ocytes. Radiating in all directions from the lacunae are tiny canaliculi
(kan-a-LIK-ū-lī = small channels), which are filled with extracellular
fluid. Inside the canaliculi are slender fingerlike processes of osteo-
cytes (see inset at right of Figure 6.3a). Neighboring osteocytes com-
municate via gap junctions (see Section 4.2). The canaliculi connect
lacunae with one another and with the central canals, forming an
intricate, miniature system of interconnected canals throughout the
bone. This system provides many routes for nutrients and oxygen to
reach the osteocytes and for the removal of wastes.
Osteons in compact bone tissue are aligned in the same direction
and are parallel to the length of the diaphysis. As a result, the shaft of
a long bone resists bending or fracturing even when considerable
force is applied from either end. Compact bone tissue tends to be
thickest in those parts of a bone where stresses are applied in rela-
tively few directions. The lines of stress in a bone are not static. They
change as a person learns to walk and in response to repeated strenu-
ous physical activity, such as weight training. The lines of stress in a
bone also can change because of fractures or physical deformity.
Thus, the organization of osteons is not static but changes over time
in response to the physical demands placed on the skeleton.
The areas between neighboring osteons contain lamellae called
interstitial lamellae (in′-ter-STISH-al), which also have lacunae with os-
teocytes and canaliculi. Interstitial lamellae are fragments of older osteons
that have been partially destroyed during bone rebuilding or growth.
Blood vessels and nerves from the periosteum penetrate the com-
pact bone through transverse interosteonic (Volkmann’s or perforat-
ing) canals. The vessels and nerves of the interosteonic canals connect
with those of the medullary cavity, periosteum, and central canals.
Arranged around the entire outer and inner circumference of
the shaft of a long bone are lamellae called circumferential lamellae
(ser′-kum-fer-EN-shē-al). They develop during initial bone formation.
The circumferential lamellae directly deep to the periosteum are
called external circumferential lamellae. They are connected to the
periosteum by perforating (Sharpey’s) fibers. The circumferential
lamellae that line the medullary cavity are called internal circumferen-
tial lamellae (Figure 6.3a).
Spongy Bone Tissue
,
In contrast to compact bone tissue, spongy bone tissue, also referred
to as trabecular or cancellous bone tissue, does not contain osteons
(Figure 6.3b, c). Spongy bone tissue is always located in the interior of
a bone, protected by a covering of compact bone. It consists of lamel-
lae that are arranged in an irregular pattern of thin columns called
trabeculae (tra-BEK-ū-lē = little beams; singular is trabecula).
Between the trabeculae are spaces that are visible to the unaided eye.
These macroscopic spaces are filled with red bone marrow in bones
that produce blood cells, and yellow bone marrow (adipose tissue) in
other bones. Both types of bone marrow contain numerous small
blood vessels that provide nourishment to the osteocytes. Each tra-
becula consists of concentric lamellae, osteocytes that lie in lacunae,
and canaliculi that radiate outward from the lacunae.
Spongy bone tissue makes up most of the interior bone tissue of
short, flat, sesamoid, and irregularly shaped bones. In long bones it
forms the core of the epiphyses beneath the paper-thin layer of com-
pact bone, and forms a variable narrow rim bordering the medullary
cavity of the diaphysis. Spongy bone is always covered by a layer of
compact bone for protection.
At first glance, the trabeculae of spongy bone tissue may appear
to be less organized than the osteons of compact bone tissue. How-
ever, they are precisely oriented along lines of stress, a characteristic
that helps bones resist stresses and transfer force without breaking.
Spongy bone tissue tends to be located where bones are not heavily
stressed or where stresses are applied from many directions. The tra-
beculae do not achieve their final arrangement until locomotion is
completely learned. In fact, the arrangement can even be altered as
lines of stress change due to a poorly healed fracture or a deformity.
Spongy bone tissue is diff erent from compact bone tissue in two
respects. First, spongy bone tissue is light, which reduces the overall
weight of a bone. This reduction in weight allows the bone to move
more readily when pulled by a skeletal muscle. Second, the trabecu-
lae of spongy bone tissue support and protect the red bone marrow.
Spongy bone in the hip bones, ribs, sternum (breastbone), vertebrae,
and the proximal ends of the humerus and femur is the only site where
red bone marrow is stored and, thus, the site where hemopoiesis
(blood cell production) occurs in adults.,Blood and Nerve Supply
of Bone
OBJECTIVE
• Describe the blood and nerve supply of bone.
Bone is richly supplied with blood. Blood vessels, which are especially
abundant in portions of bone containing red bone marrow, pass into
bones from the periosteum. We will consider the blood supply of a
long bone such as the mature tibia (shin bone) shown in Figure 6.4.
Periosteal arteries (per-ē-OS-tē-al), small arteries accompanied
by nerves, enter the diaphysis through many interosteonic
(Volkmann’s or perforating) canals and supply the periosteum and
outer part of the compact bone (see Figure 6.3a). Near the center of the
diaphysis, a large nutrient artery passes through a hole in compact
bone called the nutrient foramen (foramina is plural). On entering
the medullary cavity, the nutrient artery divides into proximal and
distal branches that course toward each end of the bone. These
branches supply both the inner part of compact bone tissue of the
diaphysis and the spongy bone tissue and red bone marrow as far as
the epiphyseal plates (or lines). Some bones, like the tibia, have only
one nutrient artery; others, like the femur (thigh bone), have several.
The ends of long bones are supplied by the metaphyseal and epiphy-
seal arteries, which arise from arteries that supply the associated
joint. The metaphyseal arteries (met-a-FIZ-ē-al) enter the metaphy-
ses of a long bone and, together with the nutrient artery, supply the
red bone marrow and bone tissue of the metaphyses. The epiphyseal
arteries (ep′-i-FIZ-ē-al) enter the epiphyses of a long bone and supply
the red bone marrow and bone tissue of the epiphyses.
Veins that carry blood away from long bones are evident in three
places: (1) One or two nutrient veins accompany the nutrient artery
and exit through the diaphysis; (2) numerous epiphyseal veins and,
metaphyseal veins accompany their respective arteries and exit
through the epiphyses and metaphyses, respectively; and (3) many
small periosteal veins accompany their respective arteries and exit
through the periosteum.
Nerves accompany the blood vessels that supply bones. The peri-
osteum is rich in sensory nerves, some of which carry pain sensations.
These nerves are especially sensitive to tearing or tension, which
explains the severe pain resulting from a fracture or a bone tumor. For
the same reason, there is some pain associated with a bone marrow
needle biopsy. In this procedure, a needle is inserted into the middle
of the bone to withdraw a sample of red bone marrow to examine it
for conditions such as leukemias, metastatic neoplasms, lymphoma,
Hodgkin’s disease, and aplastic anemia. As the needle penetrates the
periosteum, pain is felt. Once it passes through, there is little pain.
Bone Formation
،
OBJECTIVES
• Describe the steps of intramembranous and endochondral
ossification.
• Explain how bone grows in length and thickness.
• Describe the process involved in bone remodeling.
The process by which bone forms is called ossification (os′-i-fi-KA-
–
shun; ossi- = bone; -fication = making) or osteogenesis (os′-tē-ō-JEN-
e-sis). 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.
Initial Bone Formation in an Embryo
and Fetus
We will first consider the initial formation of bone in an embryo and
fetus. The embryonic “skeleton,” initially composed of mesenchyme
in the general shape of bones, is the site where cartilage formation
and ossification occur during the sixth week of embryonic develop-
ment. Bone formation follows one of two patterns.
The two patterns of bone formation, which both involve the re-
placement of a preexisting connective tissue with bone, do not lead to
diff erences in the structure of mature bones, but are simply diff erent
methods of bone development. In the first type of ossification, called
intramembranous ossification (in′-tra-MEM-bra-nus; intra- = within;
-membran- = membrane), bone forms directly within mesenchyme,
which is arranged in sheetlike layers that resemble membranes. In the
second type, endochondral ossification (en′-dō-KON-dral; endo- =
within; -chondral = cartilage), bone forms within hyaline cartilage
that develops from mesenchyme.
Intramembranous Ossification Intramembranous ossifi-
cation is the simpler of the two methods of bone formation. 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.
Also, the “soft spots” that help the fetal skull pass through the birth
canal later harden as they undergo intramembranous ossification,
which occurs as follows (Figure 6.5):
1 Development of the ossification center. At the site where the
bone will develop, specific chemical messages cause the cells
of the mesenchyme to cluster together and diff erentiate, 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 associated with the blood vessels in the
trabeculae diff erentiates into red bone marrow.
4 Development of the periosteum. In conjunction with the formation
of trabeculae, the mesenchyme condenses at the periphery of
the bone 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.
Endochondral Ossification The replacement of cartilage
by bone is called endochondral ossification. Although most bones of
the body are formed in this way, the process is best observed in a long
bone. It proceeds as follows (Figure 6.6):
1 Development of the cartilage model. At the site where the bone
is going to form, specific chemical messages cause the cells in
