Parathyroid Hormone and Calcitonin and Calcium and Phosphate pdf - Endocrinology and Reproduction

interstitial fluids (citrate and phosphate, for instance) in such a manner that it

(2) About 9 per cent of the calcium (0.2 mmol/L) is diffusible through the cap-

proteins and in this form is nondiffusible through the capillary membrane.

(1) About 41 per cent (1 mmol/L) of the calcium is combined with the plasma

The calcium in the plasma is present in three forms, as shown in Figure 79–1.

Calcium in the Plasma and Interstitial Fluid

ulated as calcium concentration, phosphate serves several important functions

15 per cent is in the cells, and less than 1 per cent is in the extracellular fluid.

Approximately 85 per cent of the body’s phosphate is stored in bones, 14 to

as large reservoirs, releasing calcium when extracellular fluid concentration

cent is in the cells, and the rest is stored in bones. Therefore, the bones can serve

0.1 per cent of the total body calcium is in the extracellular fluid, about 1 per

gressive depression of the nervous system; conversely, decreases in calcium con-

neurons, are very sensitive to changes in calcium ion concentrations, and

and transmission of nerve impulses, to name just a few. Excitable cells, such as

including contraction of skeletal, cardiac, and smooth muscles; blood clotting;

is essential, because calcium plays a key role in many physiologic processes,

9.4 mg/dl, which is equivalent to 2.4 mmol calcium per liter. This precise control

Extracellular fluid calcium concentration normally is regulated very precisely,

Overview of Calcium and Phosphate

homeostasis are closely associated, they are discussed together in this chapter.

ulated by the hormones just noted. Because phosphate homeostasis and calcium

uptake and release of calcium, each of which is reg-

the intestine, renal excretion of calcium, and bone

calcium ion concentration, for example, is deter-

are all closely intertwined. Extracellular

, and

lism, formation of bone and teeth, and regulation of

The physiology of calcium and phosphate metabo-

and Teeth

Metabolism, Vitamin D, Bone,

Parathyroid Hormone, Calcitonin,

978

Calcium and Phosphate

vitamin D, parathyroid hormone (PTH)

calci-

tonin

mined by the interplay of calcium absorption from

Regulation in the Extracellular Fluid
and Plasma

seldom rising or falling more than a few per cent from the normal value of about

increases in calcium ion concentration above normal (hypercalcemia) cause pro-

centration (hypocalcemia) cause the nervous system to become more excited.

An important feature of extracellular calcium regulation is that only about

decreases and storing excess calcium.

Although extracellular fluid phosphate concentration is not nearly as well reg-

and is controlled by many of the same factors that regulate calcium.

illary membrane but is combined with anionic substances of the plasma and

seldom evident in patients, such as marked dilatation

ally be reduced beyond the usual lethal levels, very

In laboratory animals, in which calcium can gradu-

at about 4 mg/dl.

normal calcium concentration, and it is usually lethal

to about 6 mg/dl, which is only 35 per cent below the

tion of calcium falls from its normal level of 9.4 mg/dl

Tetany ordinarily occurs when the blood concentra-

the body. This is called “carpopedal spasm.”

Figure 79–2 shows tetany in the hand, which usually

tetany. It also occasionally causes seizures because of

contraction.

Consequently,

hypocalcemia causes

excitable that they begin to discharge spontaneously,

below normal, the peripheral nerve fibers become so

ions, allowing easy initiation of action potentials. At

progressively more excitable, because this causes

falls below normal, the nervous system becomes

When

Hypocalcemia Causes Nervous System Excitement and Tetany.

bone mineralization, as explained later in the chapter.

immediate physiologic effects. In addition, chronic

body. In contrast, even slight increases or decreases of

Concentrations in the Body Fluids

of Altered Calcium and Phosphate

Non-Bone Physiologic Effects

4 mg/dl in adults and 4 to 5 mg/dl in children.

is about 4 mg/dl, varying between normal limits of 3 to

(100 ml) of blood. The average total quantity of inor-

line. These relations were presented in the discussion

, whereas the oppo-

becomes more acidic, there is a relative increase in

Furthermore, when the pH of the extracellular fluid

quantity of each of these two types of phosphate ions.

of phosphate in the extracellular fluid rises, so does the

is about 0.26 mmol/L. When the total quantity

is about 1.05 mmol/L, and the concentration of

. The concentration of

forms: HPO

Inorganic Phosphate in the

effect of calcium on the heart, the nervous system, and

most functions of calcium in the body, including the

This ionic calcium is the form that is important for

2.4 mEq/L, because it is a divalent ion), a level only

concentration of about 1.2 mmol/L (or

Thus, the plasma and interstitial fluids have a normal

is not ionized. (3) The remaining 50 per cent of the

Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

Chapter 79

979

calcium in the plasma is both diffusible through the
capillary membrane and ionized.

calcium ion

one half the total plasma calcium concentration.

bone formation.

Extracellular Fluids

Inorganic phosphate in the plasma is mainly in two

and H

HPO

and a decrease in HPO

site occurs when the extracellular fluid becomes alka-

of acid-base balance in Chapter 30.

Because it is difficult to determine chemically the

exact quantities of HPO

and H

in the blood,

ordinarily the total quantity of phosphate is expressed
in terms of milligrams of phosphorus per deciliter

ganic phosphorus represented by both phosphate ions

Changing the level of phosphate in the extracellular
fluid from far below normal to two to three times
normal does not cause major immediate effects on the

calcium ion in the extracellular fluid can cause extreme

hypocalcemia or hypophosphatemia greatly decreases

the extracellular fluid concentration of calcium ions

increased neuronal membrane permeability to sodium

plasma calcium ion concentrations about 50 per cent

initiating trains of nerve impulses that pass to the
peripheral skeletal muscles to elicit tetanic muscle

its action of increasing excitability in the brain.

occurs before tetany develops in most other parts of

extreme hypocalcemia can cause other effects that are

Protein-bound calcium

41%

(1.0 mmol/L)

Ionized calcium

50%

(1.2 mmol/L)

Calcium complexed to

anions 9% (0.2 mmol/L)

calcium complexed to anions, and nondiffusible protein-bound

), diffusible but un-ionized

Figure 79–1

Distribution of ionized calcium (Ca

calcium in blood plasma.

Figure 79–2

Hypocalcemic tetany in the hand, called carpopedal spasm.

greatly increase phosphate excretion by the kidneys,

However, as discussed later in the chapter, PTH can

the kidneys.

proportional to the additional increase. Thus, the

centration, the rate of phosphate loss is directly

phate is lost in the urine. But above this critical con-

the critical value of about 1 mmol/L, all the phosphate

as explained in Chapter 29. That is,

flow mechanism,

over-

excretion, is PTH.

nephron, and therefore controlling the rate of calcium

calcium excretion markedly. We shall see later in the

urine. Conversely, even a minute increase in blood

tion is great, so that almost no calcium is lost in the

When calcium concentration is low, this reabsorp-

selective, depending on the calcium ion concentration

ducts, reabsorption of the remaining 10 per cent is very

Then in the late distal tubules and early collecting

tubules, loops of Henle, and early distal tubules.

in the urine. Approximately 90 per cent of the calcium

the filtered calcium, and about 100 mg/day is excreted

Normally, the renal tubules reabsorb 99 per cent of

glomeruli into the renal tubules.

not filtered by the glomerular capillaries. The rest is

excreted in the urine. About 41 per cent of the plasma

10 per cent (100 mg/day) of the ingested calcium is

urine.

calcium, almost all the dietary phosphate is absorbed

easily. Except for the portion of phosphate that is

is excreted in the feces (Figure 79–3).

90 per cent (900 mg/day) of the daily intake of calcium

testinal juices and sloughed mucosal cells. Thus, about

excreted in the feces. An additional 250 mg/day of

absorbed; the calcium remaining in the intestine is

cent (350 mg/day) of the ingested calcium is usually

calcium absorption by the intestines, and about 35 per

However, as discussed later,

calcium ions are poorly absorbed from the intestines.

in 1 liter of milk. Normally, divalent cations such as

each for calcium and phosphorus, about the amounts

The usual rates of intake are about 1000 mg/day

Absorption and Excretion of Calcium

parathyroid poisoning.

tals are likely to precipitate throughout the body; this

about 17 mg/dl in the blood, calcium phosphate crys-

above 15 mg/dl. When the level of calcium rises above

blood level of calcium rises above about 12 mg/dl, and

These depressive effects begin to appear when the

lack of appetite and constipation, probably because of

sluggish. Also, increased calcium ion concentration

above normal, the nervous system becomes depressed

When the level of calcium in the body fluids rises

Hypercalcemia Depresses Nervous System and Muscle Activity.

addition to nerve cells), and impaired blood clotting.

of the heart, changes in cellular enzyme activities,

980

Unit XIV

Endocrinology and Reproduction

increased membrane permeability in some cells (in

and reflex activities of the central nervous system are

decreases the QT interval of the heart and causes

depressed contractility of the muscle walls of the gas-
trointestinal tract.

they can become marked as the calcium level rises

condition is discussed later in connection with

and Phosphate

Intestinal Absorption and Fecal Excretion of Calcium and Phos-
phate.

vitamin D promotes

calcium enters the intestines via secreted gastroin-

Intestinal absorption of phosphate occurs very

excreted in the feces in combination with nonabsorbed

into the blood from the gut and later excreted in the

Renal Excretion of Calcium and Phosphate.

Approximately

calcium is bound to plasma proteins and is therefore

combined with anions such as phosphate (9 per cent)
or ionized (50 per cent) and is filtered through the

in the glomerular filtrate is reabsorbed in the proximal

in the blood.

calcium ion concentration above normal increases

chapter that the most important factor controlling this
reabsorption of calcium in the distal portions of the

Renal phosphate excretion is controlled by an

when phosphate concentration in the plasma is below

in the glomerular filtrate is reabsorbed and no phos-

kidneys regulate the phosphate concentration in the
extracellular fluid by altering the rate of phosphate
excretion in accordance with the plasma phosphate
concentration and the rate of phosphate filtration by

thereby playing an important role in the control of
plasma phosphate concentration as well as calcium
concentration.

Bone and Its Relation
to Extracellular Calcium
and Phosphate

Bone is composed of a tough organic matrix that is
greatly strengthened by deposits of calcium salts.

Cells

(13,000 mg)

Bone

(1,000,000 mg)

Deposition

(500 mg/day)

Absorption

(500 mg/day)

Reabsorption

(9880 mg/day)

Filtration

(9980 mg/day)

Absorption

(350 mg/day)

Calcium

intake

(350 mg/day)

Feces

(900 mg/day)

Urine

(100 mg/day)

Kidneys

Secretion

(250 mg/day)

Extracellular

fluid

(1300 mg)

amounts by reducing tubular reabsorption of calcium.

feces, although the kidneys have the capacity to excrete large

that most of the ingested calcium is normally eliminated in the

ments in a person ingesting 1000 mg of calcium per day. Note

Overview of calcium exchange between different tissue compart-

Figure 79–3

Once the pyrophosphate has been neutralized, the

causing precipitation of calcium salts. The osteoblasts

theory holds that at the time of formation, the colla-

deposited in osteoid is not fully understood. One

The mechanism that causes calcium salts to be

the amorphous form. This is important because

months. A few per cent may remain permanently in

and reprecipitation, these salts are converted into

of substitution and addition of atoms, or reabsorption

O, and others. Then by a process

O, Ca

(noncrystalline), a mixture of salts such as CaHPO

The initial calcium salts to be deposited are not

hydroxyapatite

vals along each collagen fiber, forming minute nidi

collagen fibers. The precipitates first appear at inter-

Within a few days after the osteoid is formed,

and become quiescent. At this stage they are called

readily precipitate in it. As the osteoid is formed, some

, a cartilage-like

. The collagen

The initial stage in bone

ration of the ions.

. Therefore,

pyrophosphate

tation; one such inhibitor is

However, inhibitors are present in almost all tissues of

required to cause precipitation of hydroxyapatite.

The

in Bone—Equilibrium with the

of Calcium and Phosphate

Precipitation and Absorption

have great compressional strength. These combined

have great tensile strength, whereas the calcium salts

The collagen fibers of bone, like those of tendons,

overlap one another, also causing hydroxyapatite crys-

addition, the segments of adjacent collagen fibers

which is essential in providing strength to the bone. In

tals and collagen fibers from slipping out of place,

vents “shear” in the bone; that is, it prevents the crys-

the fiber, bound tightly to it.This intimate bonding pre-

Tensile and Compressional Strength of Bone.

tually develops in most cases.

deposited, an osteogenic sarcoma (bone cancer) even-

of the bone tissues, and if a sufficient amount is

. Deposition of radioactive sub-

the major radioactive products released by explosion of

, and

many ions normally foreign to bone, such as

into distinct crystals of their own. This ability of many

by them. Therefore, they are believed to be conjugated

are also present among the bone salts, although x-ray

, and

tional conditions, the Ca/P ratio on a weight basis

like a long, flat plate. The relative ratio of calcium to

angstroms thick, and 100 angstroms wide—is shaped

Each crystal—about 400 angstroms long, 10 to 30

, is the

hydroxyapatite

crystalline salt, known as

. The formula for the major

The crystalline salts deposited in the

the deposition of calcium salts.

these is not known, although they do help to control

. The precise function of each of

chondroitin sulfate

, especially

The ground substance is composed of extracellular

. The collagen fibers extend primarily along the

, and the remainder is a

The organic matrix of bone is 90

matrix in relation to salts.

per cent matrix and 70 per cent salts.

Average

Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

Chapter 79

981

compact bone contains by weight about 30

Newly formed

bone may have a considerably higher percentage of

Organic Matrix of Bone.

to 95 per cent collagen fibers
homogeneous gelatinous medium called ground sub-
stance
lines of tensional force and give bone its powerful
tensile strength.

fluid plus proteoglycans
and hyaluronic acid

Bone Salts.

organic matrix of bone are composed principally of
calcium and phosphate

following:

(PO

)

(OH)

phosphorus can vary markedly under different nutri-

varying between 1.3 and 2.0.

Magnesium, sodium, potassium

carbonate ions

diffraction studies fail to show definite crystals formed

to the hydroxyapatite crystals rather than organized

types of ions to conjugate to bone crystals extends to

strontium,

uranium, plutonium, the other transuranic elements,
lead, gold, other heavy metals

at least 9 of 14 of

the hydrogen bomb
stances in the bone can cause prolonged irradiation

Each collagen

fiber of compact bone is composed of repeating peri-
odic segments every 640 angstroms along its length;
hydroxyapatite crystals lie adjacent to each segment of

tals to be overlapped like bricks keyed to one another
in a brick wall.

properties plus the degree of bondage between the
collagen fibers and the crystals provide a bony struc-
ture that has both extreme tensile strength and
extreme compressional strength.

Extracellular Fluids

Hydroxyapatite Does Not Precipitate in Extracellular Fluid
Despite Supersaturation of Calcium and Phosphate Ions.

concentrations of calcium and phosphate ions in extra-
cellular fluid are considerably greater than those

the body as well as in plasma to prevent such precipi-

hydroxyapatite crystals fail to precipitate in normal
tissues except in bone despite the state of supersatu-

Mechanism of Bone Calcification.

production is the secretion of collagen molecules
(called collagen monomers) and ground substance
(mainly proteoglycans) by osteoblasts
monomers polymerize rapidly to form collagen fibers;
the resultant tissue becomes osteoid
material differing from cartilage in that calcium salts

of the osteoblasts become entrapped in the osteoid

osteocytes.

calcium salts begin to precipitate on the surfaces of the

that rapidly multiply and grow over a period of days
and weeks into the finished product,
crystals.

hydroxyapatite crystals but amorphous compounds

(PO

)

· 3H

the hydroxyapatite crystals over a period of weeks or

these amorphous salts can be absorbed rapidly when
there is need for extra calcium in the extracellular
fluid.

gen fibers are specially constituted in advance for

supposedly also secrete a substance into the osteoid to
neutralize an inhibitor (believed to be pyrophosphate)
that normally prevents hydroxyapatite crystallization.

Figure 79–5.

, as shown in

remains of the original cavity. Each new area of bone

, is all that

these vessels run, called the

vessels supplying the area. The canal through which

cavity until the tunnel is filled. Deposition of new bone

Bone deposition then continues for several months, the

osteoblasts instead; then new bone begins to develop.

and is several millimeters long. At the end of this time,

eats away at the bone for about 3 weeks, creating a

once a mass of osteoclasts begins to develop, it usually

clasts usually exist in small but concentrated masses, and

that the total mass of bone remains constant. Osteo-

deposition and absorption are equal to each other, so

Normally, except in growing bones, the rates of bone

particles of bone matrix and crystals, eventually also dis-

osteoclastic cells also imbibe by phagocytosis minute

bone, and the acids cause solution of the bone salts. The

The enzymes digest or dissolve the organic matrix of the

released from the mitochondria and secretory vesicles.

and (2) several acids, including citric acid and lactic acid,

enzymes, released from the lysosomes of the osteoclasts,

The villi secrete two types of substances: (1) proteolytic

forming a so-called ruffled border adjacent to the bone.

clasts send out villus-like projections toward the bone,

absorption is believed to be the following: The osteo-

adjacent to the osteoclasts. The mechanism of this

Histologically, bone absorption occurs immediately

osteoclasts.

of the bone surfaces of an adult. Later in the chapter we

monocyte-like cells formed in the bone marrow. The

(as many as 50 nuclei), derivatives of monocytes or

clasts, which are large phagocytic, multinucleated cells

formed constantly.

time in an adult), so that at least some new bone is being

the bones and in the bone cavities. A small amount of

79–4). Osteoblasts are found on the outer surfaces of

are active (Figure

, and it is continually

Deposition and Absorption of

The importance of exchangeable calcium is that it

other amorphous calcium salts.

calcium. This calcium is deposited in the bones in a

exchangeable calcium is in the bone. It normally

and the gastrointestinal tract. However, most of the

the calcium found in all tissue cells, especially in highly

with the calcium ions in the extracellular fluids.

exchangeable

minutes to about 1 hour. These effects result in great

removed from the circulating body fluids, the calcium

normal. Likewise, if large quantities of calcium ions are

or more, the calcium ion concentration returns to

to high levels. However, within 30 minutes to 1 hour

If soluble calcium salts are injected intravenously, the

Calcium Exchange Between Bone and

tissues, thereby allowing precipitation.

in these instances, the inhibitor factors that normally

degenerating tissues or in old blood clots. Presumably,

like tubes. Likewise, calcium salts frequently deposit in

abnormal conditions, they do precipitate. For instance,

never precipitate in normal tissues besides bone, under

Abnormal Conditions.

Precipitation of Calcium in Nonosseous Tissues Under

982

Unit XIV

Endocrinology and Reproduction

natural affinity of the collagen fibers for calcium salts
causes the precipitation.

Although calcium salts almost

they precipitate in arterial walls in the condition called
arteriosclerosis and cause the arteries to become bone-

prevent deposition of calcium salts disappear from the

Extracellular Fluid

calcium ion concentration may increase immediately

ion concentration again returns to normal within 30

part from the fact that the bone contains a type of

calcium that is always in equilibrium

A small portion of this exchangeable calcium is also

permeable types of cells such as those of the liver

amounts to about 0.4 to 1 per cent of the total bone

form of readily mobilizable salt such as CaHPO

and

provides a rapid buffering mechanism to keep the
calcium ion concentration in the extracellular fluids
from rising to excessive levels or falling to very low
levels under transient conditions of excess or
decreased availability of calcium.

Bone—Remodeling of Bone

Deposition of Bone by the Osteoblasts.

Bone is continually

being deposited by osteoblasts
being absorbed where osteoclasts

osteoblastic activity occurs continually in all living
bones (on about 4 per cent of all surfaces at any given

Absorption of Bone—Function of the Osteoclasts.

Bone is also

being continually absorbed in the presence of osteo-

osteoclasts are normally active on less than 1 per cent

see that PTH controls the bone absorptive activity of

soluting these and releasing the products into the blood.

Bone Deposition and Absorption Are Normally in Equilibrium.

tunnel that ranges in diameter from 0.2 to 1 millimeter

the osteoclasts disappear and the tunnel is invaded by

new bone being laid down in successive layers of con-
centric circles (lamellae) on the inner surfaces of the

ceases when the bone begins to encroach on the blood

haversian canal

deposited in this way is called an osteon

Osteoblasts

Osteoclasts

Vein

Bone

Fibrous periosteum

Figure 79–4

Osteoblastic and osteoclastic activity in the same bone.

can increase many times,

plasma, an effect that is shown in Figure 79–7. Note

First, the feedback mechanism precisely regulates

reasons.

inhibitory effect on the conversion reactions. This

this occurs in the liver. The process is a limited one,

The first step in the activation of cholecal-

the Liver.

tical to the cholecalciferol formed in the skin, except

sun prevents vitamin D deficiency. The additional

the sun. Consequently, appropriate exposure to the

stance normally in the skin, by ultraviolet rays from

, a sub-

7-dehydrocholesterol

cholecalciferol

functions. Vitamin D

D family, and they all perform more or less the same

stance from vitamin D. Let us discuss these steps.

. Figure 79–6 shows the suc-

25-dihydroxycholecalciferol

Instead, vitamin D must first be converted through a

the active substance that actually causes these effects.

tion, as discussed later. However, vitamin D itself is not

absorption from the intestinal tract; it also has impor-

Vitamin D has a potent effect to increase calcium

Vitamin D

break and often shortens convalescence.

bones, which accelerates osteoblastic activity at the

This causes stress on the opposed ends of the broken

the patient can continue to use the bone immediately.

stress to accelerate the rate of fracture healing. This is

callus.

bone. This is called a

salts, develops between the two broken ends of the

matrix, followed shortly by the deposition of calcium

“bone membrane.” Therefore, within a short time, a

stem cells in the surface tissue lining bone, called the

, which are bone

intraosseous osteoblasts involved in the break. Also,

Fracture of a bone

remodeling of bone at younger ages.

straight, especially in children because of the rapid

tion on the outer side, the bone can become almost

not compressed. After many years of increased deposi-

increased deposition of bone, and increased absorption

leg breaks in its center and then heals at an angle, the

certain circumstances. For instance, if a long bone of the

tion and calcification of bone.

bone remains thick and normally calcified. Therefore,

decalcified within a few weeks, whereas the opposite

continues to walk on the opposite leg, the bone of the

nonathletes. Also, if a person has one leg in a cast but

that the bone must carry. For instance, the bones of

deposition and absorption are slow.

son with the bones of the elderly, in whom the rates of

absorption are rapid, show little brittleness in compari-

bones of children, in whom the rates of deposition and

normal toughness of bone is maintained. Indeed, the

the old organic matrix degenerates. In this manner, the

tively brittle and weak, new organic matrix is needed as

stress patterns. Third, because old bone becomes rela-

loads. Second, even the shape of the bone can be

Consequently, bones thicken when subjected to heavy

its strength in proportion to the degree of bone stress.

cally important functions. First, bone ordinarily adjusts

The continual deposi-

Value of Continual Bone Remodeling

Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

Chapter 79

983

tion and absorption of bone have several physiologi-

rearranged for proper support of mechanical forces by
deposition and absorption of bone in accordance with

Control of the Rate of Bone Deposition by Bone “Stress.”

Bone

is deposited in proportion to the compressional load

athletes become considerably heavier than those of

leg in the cast becomes thin and as much as 30 per cent

continual physical stress stimulates osteoblastic deposi-

Bone stress also determines the shape of bones under

compression stress on the inside of the angle causes

occurs on the outer side of the angle where the bone is

tion on the inner side of the angulated bone and absorp-

Repair of a Fracture Activates Osteoblasts.

in some way maximally activates all the periosteal and

immense numbers of new osteoblasts are formed almost
immediately from osteoprogenitor cells

large bulge of osteoblastic tissue and new organic bone

Many bone surgeons use the phenomenon of bone

done by use of special mechanical fixation apparatuses
for holding the ends of the broken bone together so that

tant effects on both bone deposition and bone absorp-

succession of reactions in the liver and the kidneys to
the final active product, 1,

also called 1,25(OH)

cession of steps that lead to the formation of this sub-

Cholecalciferol (Vitamin D

) Is Formed in the Skin.

Several

compounds derived from sterols belong to the vitamin

(also called

) is

the most important of these and is formed in the skin
as a result of irradiation of

vitamin D compounds that we ingest in food are iden-

for the substitution of one or more atoms that do not
affect their function.

Cholecalciferol Is Converted to 25-Hydroxycholecalciferol in

ciferol is to convert it to 25-hydroxycholecalciferol;

because the 25-hydroxycholecalciferol has a feedback

feedback effect is extremely important for two

the concentration of 25-hydroxycholecalciferol in the

that the intake of vitamin D

Epiphyseal line

Osteon

Canaliculi

Lacunae

Haversian

canal

Magnified

section

Epiphyseal line

Structure of bone.

Figure 79–5

1,25-dihydroxycholecalciferol. Second, and even more

First, the calcium ion itself has a slight effect in pre-

calcium in the plasma. There are two reasons for this.

Figure 79–8 demonstrates that

ing the functional effects of vitamin D in the body.

Therefore, PTH exerts a potent influence in determin-

erol requires PTH. In the absence of PTH, almost

Note also in Figure 79–6 that the conversion of 25-

effectiveness.

absence of the kidneys, vitamin D loses almost all its

than 1/1000 of the vitamin D effect. Therefore, in the

ous products in the scheme of Figure 79–6 have less

the most active form of vitamin D, because the previ-

. This latter substance is by far

dihydroxycholecalciferol

Figure 79–6

many months.

the vitamin D form, it can be stored in the liver for

it persists in the body for only a few weeks, whereas in

stored in the liver for future use. Once it is converted,

Second, this controlled conversion of vitamin D

is altered over a wide range.

erol remains nearly normal. This high degree of feed-

984

Unit XIV

Endocrinology and Reproduction

and yet the concentration of 25-hydroxycholecalcif-

back control prevents excessive action of vitamin D
when intake of vitamin D

25-hydroxycholecalciferol conserves the vitamin D

Formation of 1,25-Dihydroxycholecalciferol in the Kidneys
and Its Control by Parathyroid Hormone.

also shows the conversion in the proximal tubules
of the kidneys of 25-hydroxycholecalciferol to 1,25-

hydroxycholecalciferol to 1,25-dihydroxycholecalcif-

none of the 1,25-dihydroxycholecalciferol is formed.

Calcium Ion Concentration Controls the Formation of 1,25-
Dihydroxycholecalciferol.

the plasma concentration of 1,25-dihydroxycholecal-
ciferol is inversely affected by the concentration of

venting the conversion of 25-hydroxycholecalciferol to

ATPase

1,25-Dihydroxycholecalciferol

Intestinal absorption of calcium

Plasma calcium ion concentration

25-Hydroxycholecalciferol

Cholecalciferol (vitamin D

)

Calcium-

stimulated

Alkaline

phosphatase

Inhibition

Intestinal
epithelium

Kidney

Liver

Skin

Activation

Calcium-

binding

protein

Parathyroid

hormone

and the role of vitamin D in controlling the plasma calcium

to form 1,25-dihydroxycholecalciferol

Figure 79–6

Activation of vitamin D

concentration.

0.5

1.0

1.5

2.0

1.2

1.0

0.8

0.6

0.4

0.2

2.5

Intake of vitamin D

(times normal)

Normal range

Plasma 25-

hydroxycholecalciferol

(times normal)

of activated vitamin D that is formed.

changes in vitamin D intake have little effect on the final quantity

of 25-hydroxycholecalciferol. This figure shows that tremendous

Effect of increasing vitamin D

Figure 79–7

intake on the plasma concentration

Plasma calcium (mg/100 mL)

Normal

Plasma 1,25-

hydroxycholecalciferol

(times normal)

greatly increased absorption of calcium from the intestine.

increased formation of activated vitamin D, which in turn leads to

slight decrease in calcium concentration below normal causes

tion of 1,25-dihydroxycholecalciferol. This figure shows that a

Effect of plasma calcium concentration on the plasma concentra-

Figure 79–8

transient hypoparathyroidism. But even a small quan-

causes no major physiologic abnormalities. However,

erally recognized, total or subtotal thyroidectomy fre-

reason, before the importance of these glands was gen-

just another lobule of the thyroid gland. For this

fat. The parathyroid glands are difficult to locate

limeters long, 3 millimeters wide, and 2 millimeters

of the thyroid. Each parathyroid gland is about 6 mil-

there are four parathyroid glands in humans; they are

resultant tetany.

, often with

the extracellular fluid; conversely, hypofunction of the

salts from the bones, with resultant

lar fluid and bone of these ions. Excess activity of the

renal excretion, and exchange between the extracellu-

Parathyroid Hormone

osteocytic cell membranes.

through cell membranes—but in this instance, perhaps

again, the mechanism of the effect is unknown, but it

increase, it enhances the mineralization of bone. Here

intestines. However, even in the absence of such

. One of the ways in which it does this is to

Vitamin D in smaller quantities promotes bone cal-

transport through cellular membranes.

is not known, but it is believed to result from the effect

prevented. The mechanism of this action of vitamin D

D, the effect of PTH in causing bone absorption (dis-

. In the absence of vitamin

extreme quantities of vitamin D

both bone absorption and bone deposition. The

Vitamin D plays important roles in

Hormone Activity.

substances.

stances in the urine. However, this is a weak effect

absorption by the epithelial cells of the renal tubules,

Vitamin D also increases calcium and phosphate

Vitamin D Decreases Renal Calcium and Phosphate Excretion.

phosphate.

hormone’s action on calcium absorption, the cal-

enhanced by vitamin D. It is believed that this results

Although phosphate is usually absorbed easily, phos-

details of all these effects are unclear.

line phosphatase in the epithelial cells. The precise

the formation of (1) a calcium-stimulated ATPase in

from the body, thus causing a prolonged effect on

quantity of this calcium-binding protein. Furthermore,

membrane of the cell by facilitated diffusion. The rate

these cells to transport calcium into the cell cytoplasm,

cells. This protein functions in the brush border of

increasing, over a period of about 2 days, formation of

absorption of calcium. It does this principally by

tions as a type of “hormone” to promote intestinal

to feedback regulation of these substances.

ciferol, has several effects on the intestines, kidneys,

The active form of vitamin D, 1,25-dihydroxycholecal-

Actions of Vitamin D

bones, and the renal tubules, thus causing the calcium

the absorption of calcium from the intestines, the

erol is greatly depressed. Lack of this in turn decreases

too high, the formation of 1,25-dihydroxycholecalcif-

When the plasma calcium concentration is already

when PTH is suppressed, the 25-hydroxycholecalcif-

erol in the kidneys. At higher calcium concentrations,

below this level, PTH promotes the conversion of 25-

10 mg/100 ml. Therefore, at calcium concentrations

important, as we shall see later in the chapter, the rate

Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

Chapter 79

985

of secretion of PTH is greatly suppressed when the
plasma calcium ion concentration rises above 9 to

hydroxycholecalciferol to 1,25-dihydroxycholecalcif-

erol is converted to a different compound—24,25-
dihydroxycholecalciferol—that has almost no vitamin
D effect.

ion concentration to fall back toward its normal level.

and bones that increase absorption of calcium and
phosphate into the extracellular fluid and contribute

“Hormonal” Effect of Vitamin D to Promote Intestinal Calcium
Absorption.

1,25-Dihydroxycholecalciferol itself func-

a calcium-binding protein in the intestinal epithelial

and the calcium then moves through the basolateral

of calcium absorption is directly proportional to the

this protein remains in the cells for several weeks after
the 1,25-dihydroxycholecalciferol has been removed

calcium absorption.

Other effects of 1,25-dihydroxycholecalciferol that

might play a role in promoting calcium absorption are

the brush border of the epithelial cells and (2) an alka-

Vitamin D Promotes Phosphate Absorption by the Intestines.

phate flux through the gastrointestinal epithelium is

from a direct effect of 1,25-dihydroxycholecalciferol,
but it is possible that it results secondarily from this

cium in turn acting as a transport mediator for the

thereby tending to decrease excretion of these sub-

and probably not of major importance in regulating
the extracellular fluid concentration of these

Effect of Vitamin D on Bone and Its Relation to Parathyroid

administration of
causes absorption of bone

cussed in the next section) is greatly reduced or even

of 1,25-dihydroxycholecalciferol to increase calcium

cification
increase calcium and phosphate absorption from the

probably also results from the ability of 1,25-dihy-
droxycholecalciferol to cause transport of calcium ions

in the opposite direction through the osteoblastic or

Parathyroid hormone provides a powerful mechanism
for controlling extracellular calcium and phosphate
concentrations by regulating intestinal reabsorption,

parathyroid gland causes rapid absorption of calcium

hypercalcemia in

parathyroid glands causes hypocalcemia

Physiologic Anatomy of the Parathyroid Glands.

Normally

located immediately behind the thyroid gland—one
behind each of the upper and each of the lower poles

thick and has a macroscopic appearance of dark brown

during thyroid operations because they often look like

quently resulted in removal of the parathyroid glands
as well.

Removal of half the parathyroid glands usually

removal of three of the four normal glands causes

tity of remaining parathyroid tissue is usually capable

When large quantities of PTH are injected, the

phate salts from the bone.

bone itself, not merely absorption of the calcium phos-

results from proliferation of the osteoclasts, followed

days or even weeks to become fully developed; it

second phase is a much slower one, requiring several

promote calcium and phosphate absorption. The

already existing bone cells (mainly the osteocytes) to

several hours. This phase results from activation of the

calcium and phosphate. One is a rapid phase that

Phosphate Absorption from the Bone

Parathyroid Hormone Increases Calcium and

increased phosphate absorption from the bone.

of PTH to increase renal phosphate excretion, an

excretion of calcium by the kidneys. The decline in

principally by two effects: (1) an effect of PTH to

2 hours. The rise in calcium concentration is caused

concentration, however, falls more rapidly than the

and reaches a plateau in about 4 hours. The phosphate

uing this for several hours. Note that at the onset of

Figure 79–10 shows the approximate effects on the

Concentrations in the

on Calcium and Phosphate

Effect of Parathyroid Hormone

by the fragments.

hours, a large share of the hormonal activity is caused

full PTH activity. In fact, because the kidneys rapidly

granules in the cytoplasm of the cells. The final

Golgi apparatus, and finally is packaged in secretory

mone with 90 amino acids, then to the hormone itself

of 110 amino acids. This is cleaved first to a prohor-

in the form of a preprohormone, a polypeptide chain

in a pure form. It is first synthesized on the ribosomes

Chemistry of Parathyroid Hormone.

hormone.

cells is not certain, but they are believed to be modi-

most, if not all, of the PTH. The function of the oxyphil

young humans. The chief cells are believed to secrete

, but

oxyphil cells

chief cells

shown in Figure 79–9, contains mainly

The parathyroid gland of the adult human being,

tion of all the glands.

986

Unit XIV

Endocrinology and Reproduction

of hypertrophying satisfactorily to perform the func-

and

a small to moderate number of
oxyphil cells are absent in many animals and in

fied or depleted chief cells that no longer secrete

PTH has been isolated

with 84 amino acids by the endoplasmic reticulum and

hormone has a molecular weight of about 9500.
Smaller compounds with as few as 34 amino acids
adjacent to the N terminus of the molecule have also
been isolated from the parathyroid glands that exhibit

remove the whole 84-amino acid hormone within
minutes but fail to remove many of the fragments for

Extracellular Fluid

blood calcium and phosphate concentrations caused
by suddenly infusing PTH into an animal and contin-

infusion the calcium ion concentration begins to rise

calcium rises and reaches a depressed level within 1 or

increase calcium and phosphate absorption from the
bone and (2) a rapid effect of PTH to decrease the

phosphate concentration is caused by a strong effect

effect that is usually great enough to override

PTH has two effects on bone in causing absorption of

begins in minutes and increases progressively for

by greatly increased osteoclastic reabsorption of the

Rapid Phase of Calcium and Phosphate Absorption—Osteoly-
sis.

calcium ion concentration in the blood begins to rise

Thyroid gland

Red blood cell

Oxyphil cell

Chief cell

Parathyroid gland
(located on posterior
side of the thyroid
gland)

no longer secrete PTH.

is uncertain, but they may be modified or depleted chief cells that

and secreted by the chief cells. The function of the oxyphil cells

gland. Almost all of the parathyroid hormone (PTH) is synthesized

The four parathyroid glands lie immediately behind the thyroid

Figure 79–9

Phosphate

Calcium

2.40

2.35

2.30

0.8

1.2

1.0

Hours

Calcium (mmol/L)

Phosphate (mmol/L)

Begin parathyroid hormone

during the first 5 hours of parathyroid hormone infusion at a mod-

Approximate changes in calcium and phosphate concentrations

Figure 79–10

erate rate.

tration, the concentration of cAMP increases in the

mechanism. Within a few minutes after PTH adminis-

on its target organs is mediated by the cyclic adeno-

vitamin D, as discussed earlier in the chapter.

At this point, we should be reminded again that PTH

Parathyroid Hormone Increases Intestinal

to increase calcium reabsorption, continual loss of

Were it not for the effect of PTH on the kidneys

, the early collecting ducts, and possibly the

, the

affects phosphate. The increased calcium absorption

it decreases the reabsorption of sodium, potassium,

reabsorption. Moreover, it increases the rate of reab-

ions.

Excretion and Increases Phosphate Excretion

Parathyroid Hormone Decreases Calcium

multinucleated osteoclasts.

even development of large cavities filled with large,

on the bones. Prolonged administration or secretion of

fluids, it is impossible to discern any immediate effect

osteoclastic activity. Still, even in the late stages, there

to correct the weakened state. Therefore, the late

After a few months of excess PTH, osteoclastic

osteoclastic system to become well developed, but it

clasts. Several days of excess PTH usually cause the

stages: (1) immediate activation of the osteoclasts that

up the bone over a period of weeks or months.

ondary but unknown “signal” to the osteoclasts,

the activated osteoblasts and osteocytes send a sec-

receptor proteins for PTH. Instead, it is believed that

is much clearer is its activation of the osteoclasts. Yet

Slow Phase of Bone Absorption and Calcium Phosphate

Then the calcium pump on the other side of the cell

osteocytic membrane, thus allowing calcium ions to

those amorphous bone crystals that lie near the cells.

PTH can activate the calcium pump strongly, thereby

osteocytes have receptor proteins for binding PTH.

But where does PTH fit into this picture? First,

matrix. When the pump is inactivated, the bone

without absorption of the bone’s fibrous and gel

, and it occurs

bone. This effect is called

fluid calcium concentration falls even lower, and

cytic pump becomes excessively activated, the bone

third that in the extracellular fluid. When the osteo-

bone fluid into the extracellular fluid, creating a

the osteocytic membrane pumps calcium ions from the

. Experiments suggest that

Between the osteocytic membrane and the bone is

, and it is believed to provide a membrane

This extensive system is called the

connect with the surface osteocytes and osteoblasts.

out the bone structure, and these processes also

processes extend from osteocyte to osteocyte through-

areas adjacent to the osteoclasts. In fact, long, filmy

the osteoblasts and osteocytes form a system of inter-

and its calcification. However, studies have shown that

osteocytes functioning to cause bone salt absorption,

surface.

vicinity of the osteocytes lying within the bone itself

two areas in the bone: (1) from the bone matrix in the

developed. Histological and physiologic studies have

within minutes, long before any new bone cells can be

Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

Chapter 79

987

shown that PTH causes removal of bone salts from

and (2) in the vicinity of the osteoblasts along the bone

One does not usually think of either osteoblasts or

because both these types of cells are osteoblastic in
nature and normally associated with bone deposition

connected cells that spreads all through the bone and
over all the bone surfaces except the small surface

osteocytic mem-

brane system
that separates the bone itself from the extracellular
fluid.

a small amount of bone fluid

calcium ion concentration in the bone fluid only one

calcium phosphate salts are then absorbed from the

osteolysis

fluid calcium concentration rises to a higher level,
and calcium phosphate salts are redeposited in the
matrix.

the cell membranes of both the osteoblasts and the

causing rapid removal of calcium phosphate salts from

PTH is believed to stimulate this pump by increasing
the calcium permeability of the bone fluid side of the

diffuse into the membrane cells from the bone fluid.

membrane transfers the calcium ions the rest of the
way into the extracellular fluid.

Release—Activation of the Osteoclasts.

A much better

known effect of PTH and one for which the evidence

the osteoclasts do not themselves have membrane

causing them to set about their usual task of gobbling

Activation of the osteoclastic system occurs in two

are already formed and (2) formation of new osteo-

can continue to grow for months under the influence
of strong PTH stimulation.

resorption of bone can lead to weakened bones and
secondary stimulation of the osteoblasts that attempt

effect is actually to enhance both osteoblastic and

is more bone absorption than bone deposition in the
presence of continued excess PTH.

Bone contains such great amounts of calcium in

comparison with the total amount in all the extracel-
lular fluids (about 1000 times as much) that even when
PTH causes a great rise in calcium concentration in the

PTH—over a period of many months or years—finally
results in very evident absorption in all the bones and

by the Kidneys

Administration of PTH causes rapid loss of phosphate
in the urine owing to the effect of the hormone to
diminish proximal tubular reabsorption of phosphate

PTH also increases renal tubular reabsorption of

calcium at the same time that it diminishes phosphate

sorption of magnesium ions and hydrogen ions while

and amino acid ions in much the same way that it

occurs mainly in the late distal tubules

collecting

tubules
ascending loop of Henle to a lesser extent.

calcium into the urine would eventually deplete both
the extracellular fluid and the bones of this mineral.

Absorption of Calcium and Phosphate

greatly enhances both calcium and phosphate absorp-
tion from the intestines by increasing the formation in
the kidneys of 1,25-dihydroxycholecalciferol from

Cyclic Adenosine Monophosphate Mediates the Effects of
Parathyroid Hormone.

A large share of the effect of PTH

sine monophosphate (cAMP) second messenger

exchangeable bone calcium salts. This effect is

throughout the bone, thus shifting the balance

osteolytic effect of the osteocytic membrane

1. The immediate effect is to decrease the absorptive

ways.

minutes after injection of the calcitonin, in at least two

calcium ion concentration rapidly, beginning within

some young animals, calcitonin decreases blood

concentration, but one that is relatively weak and

79–11. This provides a second hormonal feedback

citonin, which is shown by the blue line in Figure

and in humans, an increase in plasma calcium concen-

In young animals, but much less so in older animals

This contrasts with PTH secretion, which is stimulated

The primary stimulus for calcitonin secre-

ians, reptiles, and birds. Calcitonin is a 32-amino acid

of lower animals such as fish, amphib-

brachial glands

fluid between the follicles of the thyroid gland. These

, lying in the interstitial

, or

PTH. However, the quantitative role of calcitonin is

tion and, in general, has effects opposite to those of

gland, tends to

Calcitonin, a peptide hormone secreted by the thyroid

body’s extremely potent feedback system for long-

tion can double PTH secretion. This is the basis of the

hypertrophy greatly, is shown by the dashed red line;

of many weeks, thus allowing time for the glands to

The approximate chronic effect that one finds when

changed over a period of a few hours. This shows that

PTH concentration. The solid red curve shows the

Figure 79–11 shows the approximate relation

example, bone absorption caused by disuse of the

diet, (2) increased vitamin D in the diet, and (3) bone

and reduced size of the parathyroid glands. Such con-

Conversely, conditions that increase the calcium ion

the mother’s extracellular fluid is hardly measurable;

, even

calcium is usually depressed only a small amount; also,

, in which the level of

rickets

more. For instance, the parathyroid glands become

sists, the glands will hypertrophy, sometimes fivefold or

minutes; if the decreased calcium concentration per-

by Calcium Ion Concentration

Control of Parathyroid Secretion

dihydroxycholecalciferol in the kidneys. There are

osteocytes, osteoclasts, and other target cells. This

988

Unit XIV

Endocrinology and Reproduction

cAMP in turn is probably responsible for such func-
tions as osteoclastic secretion of enzymes and acids to
cause bone reabsorption and formation of 1,25-

probably other direct effects of PTH that function
independently of the second messenger mechanism.

Even the slightest decrease in calcium ion concentra-
tion in the extracellular fluid causes the parathyroid
glands to increase their rate of secretion within

greatly enlarged in

they become greatly enlarged in pregnancy
though the decrease in calcium ion concentration in

and they are greatly enlarged during lactation because
calcium is used for milk formation.

concentration above normal cause decreased activity

ditions include (1) excess quantities of calcium in the

absorption caused by factors other than PTH (for

bones).

between plasma calcium concentration and plasma

acute effect when the calcium concentration is

even small decreases in calcium concentration from
the normal value can double or triple the plasma PTH.

the calcium ion concentration changes over a period

this demonstrates that a decrease of only a fraction of
a milligram per deciliter in plasma calcium concentra-

term control of plasma calcium ion concentration.

Calcitonin

decrease plasma calcium concentra-

far less than that of PTH in regulating calcium ion
concentration.

Synthesis and secretion of calcitonin occur in the

parafollicular cells

C cells

cells constitute only about 0.1 per cent of the human
thyroid gland and are the remnants of the ultimo-

peptide with a molecular weight of about 3400.

Increased Plasma Calcium Concentration Stimulates Calcitonin
Secretion.

tion is increased plasma calcium ion concentration.

by decreased calcium concentration.

tration of about 10 per cent causes an immediate
twofold or more increase in the rate of secretion of cal-

mechanism for controlling the plasma calcium ion

works in a way opposite that of the PTH system.

Calcitonin Decreases Plasma Calcium Concentration.

activities of the osteoclasts and possibly the

in favor of deposition of calcium in the

especially significant in young animals because of
the rapid interchange of absorbed and deposited
calcium.

10 12 14

Normal levels

1000

800

600

400

200

Plasma calcium (mg/dL)

Parathyroid hormone

(ng/mL)

Plasma calcitonin

(pg/mL)

Parathyroid hormone

Acute

effect

Chronic

effect

Calcitonin

100 per cent change in parathyroid hormone concentration.

centration of only a few percentage points can cause as much as

Note especially that long-term, chronic changes in calcium con-

plasma concentrations of parathyroid hormone and calcitonin.

Approximate effect of plasma calcium concentration on the

Figure 79–11

deficiency, only the PTH mechanism seems to be really

mechanism alone.

Therefore, in very young animals, excess calcitonin can

bones, and perhaps in some cells of other tissues.

dren (but probably to a smaller extent in adults), the

increases. In young animals and possibly in young chil-

At the same time that PTH decreases, calcitonin

decreases. As already explained, this sets into play

calcium ion concentration, the rate of PTH secretion

act. Within 3 to 5 minutes after an acute increase in the

calcium in the extracellular fluid, both the parathyroid

able calcium mechanism in the bones is “buffering” the

Hormonal Control of Calcium Ion Concentration—the Second

buffer system for helping to maintain constancy of the

cially of the liver and intestine, contain a reasonable

of many of the tissues of the body, espe-

mitochondria

In addition to the buffer function of the bones, the

of the bones in about 70 minutes.

the extracellular fluid each minute. Therefore, about

the bones each minute—that is, about 1 per cent of all

Also, about 5 per cent of all the blood flows through

perhaps 1 acre or more.

exchangeable salt. This reaction is rapid because the

osition of exchangeable salt. Conversely, a decrease in

able salts and their ease of resolubility, an increase in

salts of the bone, a total of 5 to 10 grams of calcium.

The quantity of these salts that is available for

amorphous calcium phosphate compounds, probably

in the bones, discussed earlier in this chapter, are

The exchangeable calcium salts

Buffer Function of the Exchangeable Calcium in Bones—the

hypocalcemia. However, there is a first line of defense

The addition or subtraction of 0.3 gram to

gram in 1 hour. This figure compares with a

vitamin D activity, a person may absorb as much as 0.3

calcium, particularly when there is also an excess of

Conversely, after ingestion of large quantities of

day.

into the intestinal tract, and lost into the feces each

calcium can be secreted in the intestinal juices, passed

For instance, in cases of diarrhea, several grams of

from the body fluids is as much as 0.3 gram in 1 hour.

At times, the amount of calcium absorbed into or lost

Summary of Control of

in which osteoclastic activity is greatly accelerated, cal-

Paget’s disease

Also, in certain bone diseases, such as

great as 5 grams or more per day—equal to 5 to 10

children, with absorption and deposition of calcium as

tion. The effect of calcitonin in children is much

rate of absorption is slowed by calcitonin, this still has

and deposition of calcium are small, and even after the

Second, in the adult, the daily rates of absorption

bly altered, which again demonstrates the overriding

removed and calcitonin is no longer secreted, the long-

the calcitonin effect. When the thyroid gland is

stimulation of PTH secretion, which almost overrides

calcitonin on plasma calcium is twofold. First, any

The reason for the weak effect of

Calcitonin Has a Weak Effect on Plasma Calcium Concentration

the effects are opposite those of PTH, but they appear

dling in the kidney tubules and the intestines. Again,

effect on plasma calcium is mainly a transient one,

plasma calcium ion concentration. That is, the

consequently, very little prolonged effect on

over a long period, the net result is reduced

by decreased numbers of osteoblasts. Therefore,

of bone leads secondarily to osteoblastic activity,

osteoclasts. Also, because osteoclastic resorption

2. The second and more prolonged effect of

Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

Chapter 79

989

calcitonin is to decrease the formation of new

decreased numbers of osteoclasts are followed

osteoclastic and osteoblastic activity and,

lasting for a few hours to a few days at most.

Calcitonin also has minor effects on calcium han-

to be of such little import that they are seldom
considered.

in the Adult Human.

initial reduction of the calcium ion concentration
caused by calcitonin leads within hours to a powerful

term blood calcium ion concentration is not measura-

effect of the PTH system of control.

only a small effect on plasma calcium ion concentra-

greater because bone remodeling occurs rapidly in

times the total calcium in all the extracellular fluid.

citonin has a much more potent effect of reducing the
calcium absorption.

Calcium Ion Concentration

total quan-

tity of calcium in all the extracellular fluid of about
1 gram.
or from such a small amount of calcium in the extra-
cellular fluid would cause serious hypercalcemia or

to prevent this from occurring even before the
parathyroid and calcitonin hormonal feedback
systems have a chance to act.

First Line of Defense.

mainly CaHPO

or some similar compound loosely

bound in the bone and in reversible equilibrium with
the calcium and phosphate ions in the extracellular
fluid.

exchange is about 0.5 to 1 per cent of the total calcium

Because of the ease of deposition of these exchange-

the concentrations of extracellular fluid calcium and
phosphate ions above normal causes immediate dep-

these concentrations causes immediate absorption of

amorphous bone crystals are extremely small and their
total surface area exposed to the fluids of the bone is

one half of any excess calcium that appears in the
extracellular fluid is removed by this buffer function

amount of exchangeable calcium (a total of about 10
grams in the whole body) that provides an additional

extracellular fluid calcium ion concentration.

Line of Defense.

At the same time that the exchange-

and the calcitonin hormonal systems are beginning to

multiple mechanisms for reducing the calcium ion con-
centration back toward normal.

calcitonin causes rapid deposition of calcium in the

cause a high calcium ion concentration to return to
normal perhaps considerably more rapidly than can
be achieved by the exchangeable calcium-buffering

In prolonged calcium excess or prolonged calcium

only a few days.

concurrent elevation of phosphate, death can occur in

poisoning, but once such elevation develops along with

above 17 mg/dl before there is danger of parathyroid

Ordinarily, the level of calcium in the blood must rise

days.

ies throughout the body. This extensive

area of the stomach mucosa, and the walls of the arter-

of the kidneys, the thyroid gland, the acid-producing

begin to deposit in the alveoli of the lungs, the tubules

rated, so that calcium phosphate (CaHPO

absorbed from the bone. Therefore, the calcium and

usually the case, probably because the kidneys cannot

centration often rises markedly instead of falling, as is

high values. Even the extracellular fluid phosphate con-

rare occasions, extreme quantities of PTH are secreted,

When, on

depressed relaxation of the heart during diastole.

tion, abdominal pain, peptic ulcer, lack of appetite, and

peripheral nervous systems, muscle weakness, constipa-

earlier in the chapter, are depression of the central and

The effects of such elevated calcium levels, as detailed

level to rise to 12 to 15 mg/dl and, rarely, even higher.

phosphatase.

fore, one of the important diagnostic findings in hyper-

There-

alkaline phosphatase.

activity. When the osteoblasts become active, they

The cystic bone disease of hyperparathyroidism is called

from only slight trauma, especially where cysts develop.

in the form of so-called giant cell osteoclast “tumors.”

cystic areas of the bone that are filled with osteoclasts

decalcification and, occasionally, large punched-out

broken bone. Radiographs of the bone show extensive

away almost entirely. Indeed, the reason a hyper-

osteoblastic deposition, and the bone may be eaten

clastic reabsorption of bone, in severe hyperparathy-

of increased renal excretion of phosphate.

activity in the bones. This elevates the calcium ion con-

predispose to the development of such a tumor.

than in men or children, mainly because pregnancy and

secretion. The cause of primary hyperparathyroidism

parathyroid glands causes inappropriate, excess PTH

In primary hyperparathyroidism, an abnormality of the

prevent overactivity by this activated form of vitamin D.

unwanted effects, because it is sometimes difficult to

potent and much more rapid action. This can also cause

normal range. At times, it might be necessary to admin-

of calcium, keeps the calcium ion concentration in a

as 100,000 units per day, along with intake of 1 to 2 grams

tion of extremely large quantities of vitamin D, to as high

In most patients with hypothyroidism, the administra-

effective, hypoparathyroidism is usually not treated

because the tendency of the body to develop anti-

because its effect lasts for a few hours at most, and

However, because of the expense of this hormone,

Treatment of Hypoparathyroidism with PTH and Vitamin D.

of these muscles obstructs respiration, which is the usual

sitive to tetanic spasm are the laryngeal muscles. Spasm

develop. Among the muscles of the body especially sen-

low calcium level is reached, the usual signs of tetany

blood phosphate concentration may double. When this

9.4 mg/dl to 6 to 7 mg/dl within 2 to 3 days, and the

When the parathyroid glands are suddenly removed,

usually remains strong.

phates are not being absorbed from the bone, the bone

body fluids decreases. Yet, because calcium and phos-

totally inactive. As a result, calcium reabsorption from

PTH, the osteocytic reabsorption of exchangeable

When the parathyroid glands do not secrete sufficient

Vitamin D, and

Parathyroid Hormone,

tion from the gut and calcium excretion in the urine.

calcium, the long-term control of extracellular calcium

of calcium or, oppositely, becomes saturated with

by PTH. Yet, when the bone reservoir either runs out

buffer-reservoir of calcium that can be manipulated

out of calcium. Thus, in effect, the bones are a large

year or more, but eventually, even the bones will run

ciency of calcium in the diet, PTH often can stimulate

concentration. When a person has a continuing defi-

990

Unit XIV

Endocrinology and Reproduction

important in maintaining a normal plasma calcium ion

enough calcium absorption from the bones to main-
tain a normal plasma calcium ion concentration for 1

ion concentration resides almost entirely in the roles
of PTH and vitamin D in controlling calcium absorp-

Pathophysiology of

Bone Disease

Hypoparathyroidism

calcium decreases and the osteoclasts become almost

the bones is so depressed that the level of calcium in the

the calcium level in the blood falls from the normal of

cause of death in tetany unless appropriate treatment is
applied.

PTH

is occasionally used for treating hypoparathyroidism.

bodies against it makes it progressively less and less

with PTH administration.

ister 1,25-dihydroxycholecalciferol instead of the nonac-
tivated form of vitamin D because of its much more

Primary Hyperparathyroidism

ordinarily is a tumor of one of the parathyroid glands;
such tumors occur much more frequently in women

lactation stimulate the parathyroid glands and therefore

Hyperparathyroidism causes extreme osteoclastic

centration in the extracellular fluid while usually
depressing the concentration of phosphate ions because

Bone Disease in Hyperparathyroidism.

Although in mild

hyperparathyroidism new bone can be deposited
rapidly enough to compensate for the increased osteo-

roidism the osteoclastic absorption soon far outstrips

parathyroid person seeks medical attention is often a

Multiple fractures of the weakened bones can result

osteitis fibrosa cystica.

Osteoblastic activity in the bones also increases

greatly in a vain attempt to form enough new bone to
make up for the old bone absorbed by the osteoclastic

secrete large quantities of

parathyroidism is a high level of plasma alkaline

Effects of Hypercalcemia in Hyperparathyroidism.

Hyper-

parathyroidism can at times cause the plasma calcium

Parathyroid Poisoning and Metastatic Calcification

the level of calcium in the body fluids rises rapidly to

excrete rapidly enough all the phosphate being

phosphate in the body fluids become greatly supersatu-

) crystals

metastatic dep-

osition of calcium phosphate can develop within a few

in adults, especially in old age. It is different from osteo-

D–resistant rickets

of calcium and vitamin D, and it is called

phosphates by the renal tubules. This type of rickets

severe one.

hemodialysis, the problem of renal rickets is often a

vitamin D. In patients whose kidneys have been

form 1,25-dihydroxycholecalciferol, the active form of

prolonged kidney damage.

The cause of this

rickets” is a type of osteomalacia that results from

disability.

rickets can occur, although this almost never proceeds

feces. Under these conditions, an adult occasionally has

rhea, both vitamin D and calcium tend to pass into the

form insoluble soaps with fat; consequently, in steator-

bone growth as in children. However, serious deficien-

deficiency of vitamin D or calcium

of vitamin D. If vitamin D is not administered, little

and, equally important, on administering large amounts

The treatment of rickets depends on

Treatment of Rickets.

relieves the tetany immediately.

unless intravenous calcium is administered, which

falls below 7 mg/dl, the usual signs of tetany develop,

calcium may fall rapidly. As the blood level of calcium

bones finally become exhausted of calcium, the level of

calcium in the extracellular fluid. However, when the

and, therefore, maintain an almost normal level of

In the early stages of rickets, tetany

Tetany in Rickets

cified, and weak osteoid gradually takes the place of the

phosphate ions. Consequently, the newly formed, uncal-

down large quantities of osteoid, which does not

rapid osteoblastic activity as well. The osteoblasts lay

imposes marked physical stress on the bone, resulting in

extreme osteoclastic absorption of the bone; this in turn

During prolonged rickets, the

Rickets Weakens the Bones

excretion of phosphates in the urine.

system for preventing a falling level of phosphate, and

begins to fall. However, there is no good regulatory

greatly depressed. This is because the parathyroid

is only slightly depressed, but the level of phosphate is

The plasma calcium concentration in rickets

first few months of vitamin D deficiency.

months. Also, calcium and phosphate absorption from

without some supplementation in the diet. Rickets tends

intestines, as discussed earlier in the chapter.

, which prevents rickets by

adequately exposed to sunlight, the 7-dehydrocholes-

fluid, usually caused by lack of vitamin D. If the child is

calcium or phosphate deficiency in the extracellular

Rickets occurs mainly in children. It results from

Vitamin D De

high levels of PTH cause absorption of the bones.

(inadequate mineralization of the bones), and

the next section, the vitamin D deficiency leads to

dihydroxycholecalciferol. As discussed in more detail in

amounts of the active form of vitamin D, 1,25-

vitamin D deficiency or chronic renal disease in which

contrasts with primary hyperparathyroidism, which is

as a primary abnormality of the parathyroid glands. This

In secondary hyperparathyroidism, high levels of PTH

acid urine. For this reason, acidotic diets and acidic

alkaline media, the tendency for formation of renal

cause calcium precipitation at high calcium levels.

forming calcium phosphate stones.Also, calcium oxalate

calcium phosphate tend to precipitate in the kidney,

of these substances in the urine. As a result, crystals of

roidism must eventually be excreted by the kidneys,

tendency to form kidney stones. The reason is that the

result of elevated calcium, but they do have an extreme

Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

Chapter 79

991

Formation of Kidney Stones in Hyperparathyroidism

Most

patients with mild hyperparathyroidism show few signs
of bone disease and few general abnormalities as a

excess calcium and phosphate absorbed from the intes-
tines or mobilized from the bones in hyperparathy-

causing a proportionate increase in the concentrations

stones develop because even normal levels of oxalate

Because the solubility of most renal stones is slight in

calculi is considerably greater in alkaline urine than in

drugs are frequently used for treating renal calculi.

Secondary Hyperparathyroidism

occur as a compensation for hypocalcemia rather than

associated with hypercalcemia.

Secondary hyperparathyroidism can be caused by

the damaged kidneys are unable to produce sufficient

osteo-

malacia

Rickets—

ficiency

terol in the skin becomes activated by the ultraviolet
rays and forms vitamin D

promoting calcium and phosphate absorption from the

Children who remain indoors through the winter in

general do not receive adequate quantities of vitamin D

to occur especially in the spring months because vitamin
D formed during the preceding summer is stored in the
liver and available for use during the early winter

the bones can prevent clinical signs of rickets for the

Plasma Concentrations of Calcium and Phosphate Decrease
in Rickets

glands prevent the calcium level from falling by pro-
moting bone absorption every time the calcium level

the increased parathyroid activity actually increases the

marked compensatory increase in PTH secretion causes

causes the bone to become progressively weaker and

become calcified because of insufficient calcium and

older bone that is being reabsorbed.

almost never occurs because the parathyroid glands
continually stimulate osteoclastic absorption of bone

and the child may die of tetanic respiratory spasm

supplying adequate calcium and phosphate in the diet

calcium and phosphate are absorbed from the gut.

Osteomalacia—“Adult Rickets”.

Adults seldom have a

serious dietary
because large quantities of calcium are not needed for

cies of both vitamin D and calcium occasionally
occur as a result of steatorrhea (failure to absorb fat)
because vitamin D is fat-soluble and calcium tends to

such poor calcium and phosphate absorption that adult

to the stage of tetany but often is a cause of severe bone

Osteomalacia and Rickets Caused by Renal Disease.

“Renal

condition is mainly failure of the damaged kidneys to

removed or destroyed and who are being treated by

Another type of renal disease that leads to rickets

and osteomalacia is congenital hypophosphatemia,
resulting from congenitally reduced reabsorption of

must be treated with phosphate compounds instead

vitamin

Osteoporosis—Decreased
Bone Matrix

Osteoporosis is the most common of all bone diseases

Also, it increases in thickness and strength with age,

layer of cementum becomes thicker and stronger.

When the teeth are exposed to excessive strain, the

gen fibers and the cementum hold the tooth in place.

membrane, and then into the cementum. These colla-

from the bone of the jaw, through the periodontal

the tooth socket. Many collagen fibers pass directly

, which lines

might result when the teeth are struck by solid objects.

ant to compressional forces, and the collagen fibers

The calcium salts in dentin make it extremely resist-

of the pulp cavity.

, which line its inner surface along the wall

clasts, or spaces for blood vessels or nerves. Instead, it

does not contain any osteoblasts, osteocytes, osteo-

ference is its histological organization, because dentin

very much the same as those of bone. The major dif-

In other words, the principal constituents of dentin are

are imbedded in a strong meshwork of collagen fibers.

to those in bone but much more dense. These crystals

dentin, which has a strong, bony structure. Dentin is

The main body of the tooth is composed of

makes enamel resistant to acids, enzymes, and other

constituting only about 1 per cent of the enamel mass,

Also, the special protein fiber meshwork, although

The crystalline structure of the salts makes the

keratin of hair.

carbonate, magnesium, sodium, potassium, and other

formed. Enamel is composed of very large and very

Once the tooth has erupted, no more enamel is

ameloblasts.

The outer surface of the tooth is covered by a

neck

The collar between the crown and the root where the

which is the portion within the bony socket of the jaw.

trudes out from the gum into the mouth, and the

, which is the portion that pro-

crown

. The tooth can also be

, and

demonstrating its major functional parts: the

Figure 79–12 shows a sagittal section of a tooth,

of the Teeth

Function of the Different Parts

between the tooth surfaces.

the lower. This fitting is called

that interdigitate, so that the upper set of teeth fits with

the jaw teeth, 150 to 200 pounds. Also, the upper and

perform these functions, the jaws have powerful

The teeth cut, grind, and mix the food eaten. To

Physiology of the Teeth

cause osteoporosis.

many diseases of deficiency of protein metabolism can

specific effect of depressing osteoblastic activity. Thus,

, because massive

Cushing’s syndrome

torily; and (6)

age, so that bone matrix cannot be deposited satisfac-

growth factors diminish greatly, plus the fact that many

, in which growth hormone and other

clasts; (5)

postmenopausal lack of estrogen secretion

cells, including formation of osteoid by the osteoblasts;

, which is nec-

lack of vitamin C

cannot be formed; (3)

because of inactivity; (2)

lack

The many common causes of osteoporosis are (1)

diminished bone is excess osteoclastic activity.

sionally, as in hyperparathyroidism, the cause of the

rate of bone osteoid deposition is depressed. But occa-

bone usually is less than normal, and consequently the

fication. In osteoporosis the osteoblastic activity in the

992

Unit XIV

Endocrinology and Reproduction

malacia and rickets because it results from diminished
organic bone matrix rather than from poor bone calci-

of physical stress on the bones
malnutrition to the extent that sufficient protein matrix

essary for the secretion of intercellular substances by all

(4)

because

estrogens decrease the number and activity of osteo-

old age

of the protein anabolic functions also deteriorate with

quantities of glucocorticoids secreted in this disease
cause decreased deposition of protein throughout the
body and increased catabolism of protein and have the

muscles capable of providing an occlusive force
between the front teeth of 50 to 100 pounds and for

lower teeth are provided with projections and facets

occlusion, and it allows

even small particles of food to be caught and ground

enamel,

dentin, cementum

pulp

divided into the

root,

tooth is surrounded by the gum is called the

Enamel.

layer of enamel that is formed before eruption of the
tooth by special epithelial cells called

dense crystals of hydroxyapatite with adsorbed

ions imbedded in a fine meshwork of strong and
almost insoluble protein fibers that are similar in phys-
ical characteristics (but not chemically identical) to the

enamel extremely hard-much harder than the dentin.

corrosive agents because this protein is one of the
most insoluble and resistant proteins known.

Dentin.

made up principally of hydroxyapatite crystals similar

is deposited and nourished by a layer of cells called
odontoblasts

make it tough and resistant to tensional forces that

Cementum.

Cementum is a bony substance secreted

by cells of the periodontal membrane

Cementum

Dentin

Pulp chamber

Enamel

Crown

Root

Neck

Functional parts of a tooth.

Figure 79–12

in bone. Deposition and reabsorption occur mainly in

old salts are being reabsorbed from the teeth, as occurs

Also, new salts are constantly being deposited while

cations bound together in a hard crystalline substance.

The salts of teeth, like those of bone, are composed of

Mineral Exchange in Teeth

tive, so that the teeth will be abnormal throughout life.

cient, the calcification of the teeth also may be defec-

be correspondingly healthy, but when they are defi-

all these factors are normal, the dentin and enamel will

vitamin D present, and the rate of PTH secretion.When

calcium and phosphate in the diet, the amount of

factors of metabolism, such as the availability of

hormones. Also, the deposition of salts in the early-

The rate of development and the speed of eruption of

uence Development of the Teeth.

Metabolic Factors In

the place of the original one.

Soon thereafter, the permanent tooth erupts to take

bone. In so doing, it erodes the root of the deciduous

like the deciduous tooth, pushes outward through the

When each permanent tooth becomes fully formed, it,

nent teeth throughout the first 6 to 20 years of life.

These tooth-producing organs slowly form the perma-

will be needed after the deciduous teeth are gone.

onic life, a tooth-forming organ also develops in the

Development of the Permanent Teeth.

offered in an attempt to explain this phenomenon. The

tion” is unknown, although several theories have been

oral epithelium into the mouth. The cause of “erup-

During early childhood, the teeth

Eruption of Teeth.

shown in Figure 79–13

formed on the inside, giving rise to an early tooth, as

is formed on the outside of the tooth, and dentin is

and the odontoblasts that secrete dentin. Thus, enamel

the tooth. The epithelial cells below invaginate upward

ameloblasts, which form the enamel on the outside of

producing organ. The epithelial cells above form

; this is followed by the development of a tooth-

tion and eruption of teeth. Figure 79–13

Figure 79–13 shows the forma-

Formation of the Teeth.

does not occur in everyone.

finally appear, which

wisdom teeth

number of permanent teeth 28 to 32, depending on

appear posteriorly in the jaws, making the total

tooth replaces it, and an additional 8 to 12 molars

year. After each deciduous tooth is lost, a permanent

2nd year of life, and they last until the 6th to the 13th

humans. They erupt between the 7th month and the

, and they number 20 in

milk teeth

, or

teeth during a lifetime. The first teeth are called the

for exchange of calcium, phosphate, and other miner-

all the way through the dentin; they are of importance

However, the odontoblasts are still viable and send

the pulp cavity remains essentially constant in size.

it smaller. In later life, the dentin stops growing and

encroach more and more on the pulp cavity, making

of the tooth, lay down the dentin but at the same time

are the odontoblasts, which, during the formative years

phatics. The cells lining the surface of the pulp cavity

dant supply of nerve fibers, blood vessels, and lym-

The pulp cavity of each tooth is filled with

jaws by adulthood and later.

Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

Chapter 79

993

causing the teeth to become more firmly seated in the

Pulp.

pulp,

which is composed of connective tissue with an abun-

projections into small dentinal tubules that penetrate

als with the dentin.

Dentition

Humans and most other mammals develop two sets of

deciduous teeth

whether the four

A shows

invagination of the oral epithelium into the dental
lamina

into the middle of the tooth to form the pulp cavity

begin to protrude outward from the bone through the

most likely theory is that growth of the tooth root as
well as of the bone underneath the tooth progressively
shoves the tooth forward.

During embry-

deeper dental lamina for each permanent tooth that

tooth and eventually causes it to loosen and fall out.

teeth can be accelerated by both thyroid and growth

forming teeth is affected considerably by various

hydroxyapatite with adsorbed carbonates and various

the dentin and cementum and to a very limited extent

Dentin

Enamel

Primordium of
enamel organ of
permanent tooth

Enamel organ

of milk tooth

Mesenchymal primordium of pulp

Oral epithelium

Alveolar bone

, Primordial tooth organ.

Figure 79–13

B, Developing tooth. C, Erupting tooth.

differentiation. Endocr Rev 23:763, 2002.

dihydroxyvitamin D(3): implications in cell growth and

factor/cytokine synthesis and signaling by 1alpha,25-

Gurlek A, Pittelkow MR, Kumar R: Modulation of growth

new PTH assays in renal osteodystrophy. Kidney Int 63:1,

Parathyroid hormone (PTH), PTH-derived peptides, and

Goodman WG, Juppner H, Salusky IB, Sherrard DJ:

Lancet 359:2018, 2002.

Delmas PD: Treatment of postmenopausal osteoporosis.

Compston JE: Sex steroids and bone. Physiol Rev 81:419,

Renal Physiol 286:F1005, 2004.

receptor in parathyroid gland physiology. Am J Physiol

Chen RA, Goodman WG: Role of the calcium-sensing

primary hyperparathyroidism. N Engl J Med 350:1746,

Bilezikian JP, Silverberg SJ: Clinical practice. Asymptomatic

porosis. JAMA 285:1415, 2001.

Altkorn D, Vokes T: Treatment of postmenopausal osteo-

applied pressure.

on the tensional side of the tooth. In this way, the tooth

teeth with appropriate braces. The gentle pressure

The orthodontist can usually correct malocclusion

the upper jaw, causing such undesirable effects as pain

adequately. Malocclusion occasionally also results in

jaw to grow to abnormal positions. In malocclusion,

caries as teeth without fluorine.

phosphate to “heal” the enamel surface. Regardless of

Finally, when small pits do develop in the enamel, flu-

soluble. Fluorine may also be toxic to the bacteria.

tals, which in turn makes the enamel several times less

enamel harder than usual, but fluorine ions replace

not contain fluorine. Fluorine does not make the

Teeth formed in chil-

metabolic substrate for many hours of the day, and the

candy, the bacteria are supplied with their preferential

parcels throughout the day, such as in the form of

is important. If carbohydrates are eaten in many small

ingested but the frequency with which it is eaten that

However, it is not the quantity of carbohydrate

content will lead to excessive development of caries.

carbohydrates for their nutrition, it has frequently

the high degree of solubility of the dentin salts.

dentin, it proceeds many times as rapidly because of

in volume as each dentin crystal. Once the carious

because the crystals of enamel are dense, but also

demineralization by acids than is dentin, primarily

development of caries. Enamel is far more resistant to

The enamel of the tooth is the primary barrier to the

olytic enzymes.

And once the salts have become absorbed, the remain-

and proteolytic enzymes. The acids are the major

In addition, they form acids (particularly lactic acid)

bolic systems are strongly activated and they multiply.

food. When carbohydrates are available, their meta-

are readily available to cause caries. These bacteria

cipitated products of saliva and food, on the teeth.

, a film of pre-

. The first event in the develop-

of bacteria on the teeth, the most common of which is

the upper and lower teeth to interdigitate properly.

. Caries refers to erosion of the teeth,

The two most common dental abnormalities are

Dental Abnormalities

ment throughout life.

enamel exhibits extremely slow mineral exchange, so

anism of this exchange in dentin is unclear. However,

the dentin and cementum of teeth, although the mech-

In summary, continual mineral exchange occurs in

mineral exchange.

have these characteristics, as explained earlier. This

of osteoblasts and osteoclasts, whereas dentin does not

identical to those of usual bone, including the presence

that of bone. The cementum has characteristics almost

ing bone of the jaw, whereas the rate of deposition and

The rate of absorption and deposition of minerals in

saliva instead of with the fluids of the pulp cavity.

in the enamel. In the enamel, these processes occur

994

Unit XIV

Endocrinology and Reproduction

mostly by diffusional exchange of minerals with the

the cementum is about equal to that in the surround-

absorption of minerals in the dentin is only one third

difference undoubtedly explains the different rates of

that it maintains most of its original mineral comple-

caries

and malocclusion
whereas malocclusion is failure of the projections of

Caries and the Role of Bacteria and Ingested Carbohydrates.

It is generally agreed that caries result from the action

Streptococcus mutans
ment of caries is the deposit of plaque

Large numbers of bacteria inhabit this plaque and

depend to a great extent on carbohydrates for their

culprit in causing caries because the calcium salts of
teeth are slowly dissolved in a highly acidic medium.

ing organic matrix is rapidly digested by the prote-

because each enamel crystal is about 200 times as large

process has penetrated through the enamel to the

Because of the dependence of the caries bacteria on

been taught that eating a diet high in carbohydrate

development of caries is greatly increased.

Role of Fluorine in Preventing Caries.

dren who drink water that contains small amounts of
fluorine develop enamel that is more resistant to caries
than the enamel in children who drink water that does

many of the hydroxyl ions in the hydroxyapatite crys-

orine is believed to promote deposition of calcium

the precise means by which fluorine protects the teeth,
it is known that small amounts of fluorine deposited in
enamel make teeth about three times as resistant to

Malocclusion.

Malocclusion is usually caused by a

hereditary abnormality that causes the teeth of one

the teeth do not interdigitate properly and therefore
cannot perform their normal grinding or cutting action

abnormal displacement of the lower jaw in relation to

in the mandibular joint and deterioration of the teeth.

by applying prolonged gentle pressure against the

causes absorption of alveolar jaw bone on the com-
pressed side of the tooth and deposition of new bone

gradually moves to a new position as directed by the

References

2004.

2001.

2003.

people. BMJ 327:89, 2003.

Woolf AD, Akesson K: Preventing fractures in elderly

Wharton B, Bishop N: Rickets. Lancet 362:1389, 2003.

Rev 81:1567, 2001.

Tordoff MG: Calcium: taste, intake, and appetite. Physiol

283:F367, 2002.

hyperparathyroidism. Am J Physiol Renal Physiol

Silver J, Kilav R, Naveh-Many T: Mechanisms of secondary

calcium-transporting epithelia, News Physiol Sci 18:158,

Peng JB, Brown EM, Hediger MA: Apical entry channels in

diagnosis, and therapy. JAMA 285:785, 2001.

vention, Diagnosis, and Therapy. Osteoporosis prevention,

N Engl J Med 343:1863, 2000.

Marx SJ: Hyperparathyroid and hypoparathyroid disorders.

22:477, 2001.

fractures and therapeutic implications. Endocr Rev

roidism in the elderly: consequences for bone loss and

Lips P: Vitamin D deficiency and secondary hyperparathy-

phia: WB Saunders Co, 2003.

Williams Textbook of Endocrinology, 10th ed. Philadel-

Larsen PR, Kronenberg HM, Melmed S, Polonsky KS:

78:1193, 1998.

of the molecular actions of vitamin D. Physiol Rev

Jones G, Strugnell SA, DeLuca HF: Current understanding

signalling. Nat Rev Mol Cell Biol 4:530, 2003.

Hofer AM, Brown EM: Extracellular calcium sensing and

Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

Chapter 79

995

NIH Consensus Development Panel on Osteoporosis Pre-

2003.