Mineral Metabolism
C signal transduction pathway. Secretion o f calcitonin is
stim ulated by hypercalcem ia but the effect o f the horm one
on calcium transport appears to be secondary to increased
phosphate uptake by target cells. The num ber and activity
o f osteoclasts are decreased, and urinary excretion o f hy-
droxyproline is decreased, C alcitonin m ay also inhibit re-
lease o f calcium from the extracellular fluid calcium pool,
but it increases calcium and phosphate excretion by renal
tubules. S om e tubular cells respond to calcitonin, PTH,
and vasopressin, w hile others respond on ly to one or tw o
o f these horm ones. In general, the actions o f calcitonin in
kidney and in bone are antagonistic to those o f PTH. C al-
citonin decreases secretion o f gastrin and o f gastric acid,
and inhibits bile flow.
T he exact biological role o f calcitonin rem ains elusive.
N either deficiency nor excess seem s to produce pathologi-
cal changes. C alcitonin m ay prevent hypercalcem ia during
childhood w hen calcium intake is high, or it m ay be im -
portant in adults during periods o f hypercalcem ia or high
calcium intake.
C alcitonin is a useful marker for m edullary carci-
nom a o f the thyroid, w hich occurs both sporadically
and as a dom inantly inherited disease.
In this type
o f tumor, the plasm a concentration o f calcitonin is 1-
1000 m g/m L (normal concentration ranges from unde-
tectable to 0.05 ng/m L). A lso, urinary hydroxyproline e x -
cretion is decreased. E ctopic secretion o f calcitonin also
occurs from several types o f pulm onary tumor in addition
to other horm ones.
C alcitonin is used in the treatm ent o f
Paget’s dis-
(osteitis deform ans), a chronic disorder character-
ized by increased bone rem odeling, norm ocalcem ia and
norm ophosphatem ia, frequent ep isod es o f hypercalciuria
leading to stone form ation, and elevation o f serum alka-
line phosphatase and urinary hydroxyproline levels. The
d isease does not appear to be primarily a derangem ent
o f calcium m etabolism . C alcitonin reduces the levels o f
serum alkaline phosphatase and urinary hydroxyproline,
and m ay relieve other sym ptom s o f the disease as w ell.
D iphosphonates, especially etidronate disodium , also re-
duce bone resorption in this disease. Various cancers are
accom panied by hypercalcem ia and m ay respond to treat-
m ent with calcitonin.
Disorders of Calcium and Phosphorus Homeostasis
Several disorders have already been discussed; the fo llo w -
ing are additional disorders o f calcium and phosphorus
hom eostasis. In
in children and
adults, there is failure o f m ineralization o f osteoid, with
consequent “softening” o f bones. In rickets, there is d efec-
tive m ineralization o f bone and o f the cartilaginous matrix
o f the epiphyseal growth plates. In osteom alacia, since the
epiphyseal plates are closed , only bone is affected. The
m ost com m on cause is deficiency o f vitam in D or, more
rarely, deficiency o f l,2 5 -(O H )2D . Characteristic find-
ings are eucalcem ia or hypocalcem ia, hypophosphatem ia,
hypocalciuria, and elevated serum alkaline phosphatase.
H ypocalcem ia or hypophosphatem ia due to inadequate di-
etary intake or excess urinary loss o f calcium or phosphate,
respectively, causes identical lesions.
The m ost com m on m etabolic bone disease is
w hich results from m any environm ental factors such
as poor diet, sm oking, alcohol consum ption, and lack o f
exercise. H owever, recent evidence indicates that genetic
variation m ay be the m ost important factor in the deter-
m ination o f bone m ass, developm ent o f osteoporosis, and
the risk o f fracture. O steoporosis can occur at any age.
Poor diet and lack o f exercise early in life contribute to
the developm ent o f osteoporosis later in life, particularly
in genetically susceptible individuals. Thus, the seeds o f
osteoporosis are sow n early in life. Lack o f intake o f cal-
cium and vitam in D in adequate quantities and an insuffi-
cient am ount o f w eight bearing exercise (e.g., w alking and
running but not sw im m ing) leads to failure in achieving
peak bone m ass in late ad olescen ce and early adulthood.
Under normal conditions, skeletal m ass is a balance be-
tw een bone form ation, bone resorption, bone cell prolifer-
ation, and apoptosis. O nly recently has it been recognized
that the skeleton is a d elicately balanced regenerating tis-
sue, regulated as precisely as the destruction and synthesis
o f blood cells.
An estim ated 75 m illion people are affected by osteo-
porosis to som e degree in the U nited States, Europe, and
Japan. O steoporosis is a system atic skeletal disease char-
acterized by bone m ass and m icroarchitectural deteriora-
tion with a consequent increase in bone fragility and sus-
ceptibility to fracture. O perationally, osteoporosis can be
defined as a certain level o f bone mineral density. The def-
inition o f osteoporosis is som ew hat arbitrary and is based
on epidem iological data relating fracture incidence to bone
m ass. Uncertainty also is introduced due to variability in
bone densitom etry m easurem ents. Other clinical measures
to assess the skeleton include collagen cross-links (m ea-
sure o f bone resorption) and levels o f bone-specific alka-
line phosphatase and osteocalcin (bone form ation). A list
o f biochem ical markers o f bone rem odeling is provided
in Table 37-3. M easurem ent o f total serum alkaline phos-
phatase level and urinary hydroxyproline or calcium levels
is o f lim ited value.
O steoporosis requires both increased resorption and one
or m ore defects in bone form ation. D uring adolescence,
the rate o f bone form ation is higher than the rate o f bone
resorption; in older persons the rate o f bone resorption
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