188
UNIT 2
Covering, Support, and Movement of the Body
6
through an additional pathway mediated by the hypothalamus,
which activates sympathetic nerves serving bones. However, the
full scope of leptin’s bone-modifying activity in humans is still
being worked out.
It is also evident that the brain, intestine, and skeleton have
ongoing conversations that help regulate the balance between
bone formation and destruction, with serotonin serving as a
hormonal go-between.
Serotonin
is better known as a neu-
rotransmitter that regulates mood and sleep, but most of the
body’s serotonin is made in the gut (intestine) and the blood-
brain barrier (see Chapter 12) bars it from entering the brain.
Te role of gut serotonin is still poorly understood. What is
known is that when we eat, serotonin is secreted and circulated
via the blood to the bones where it interferes with osteoblast ac-
tivity. Reduction of bone turnover aFer eating may lock calcium
in bone when new calcium is flooding into the bloodstream.
Tis is a troubling finding for those taking Prozac and other
antidepressant drugs that inhibit serotonin uptake, making it
more available to bone cells. Such patients have lower bone den-
sity and suffer more fractures than people not taking these drugs.
Response to Mechanical Stress
Te second set of controls
regulating bone remodeling, bone’s response to mechanical
stress (muscle pull) and gravity, keeps the bones strong where
stressors are acting.
Wolff’s law
holds that a bone grows or remodels in response
to the demands placed on it. Te first thing to understand is
that a bone’s anatomy reflects the common stresses it encoun-
ters. ±or example, a bone is loaded (stressed) whenever weight
bears down on it or muscles pull on it. Tis loading is usually
off center and tends to bend the bone. Bending compresses the
bone on one side and subjects it to tension (stretching) on the
other
(Figure 6.13)
.
When blood levels of ionic calcium decline, P²H is released
(Figure 6.12)
. Te increased P²H level stimulates osteoclasts
to resorb bone, releasing calcium into blood. Osteoclasts are no
respecters of matrix age: When activated, they break down both
old and new matrix. As blood concentrations of calcium rise,
the stimulus for P²H release ends. Te decline of P²H reverses
its effects and causes blood Ca
2
1
levels to fall.
In humans, calcitonin appears to be a hormone in search of a
function because its effects on calcium homeostasis are negligi-
ble. When administered at pharmacological (abnormally high)
doses, it does lower blood calcium levels temporarily.
Tese hormonal controls act to preserve blood calcium
homeostasis, not the skeleton’s strength or well-being. In fact,
if blood calcium levels are low for an extended time, the bones
become so demineralized that they develop large, punched-out-
looking holes. Tus, the bones serve as a storehouse from which
ionic calcium is drawn as needed.
Homeostatic Imbalance
6.1
Minute changes from the homeostatic range for blood calcium
can lead to severe neuromuscular problems ranging from hyper-
excitability (when blood Ca
2
1
levels are too low) to nonrespon-
siveness and inability to function (with high blood Ca
2
1
levels).
In addition, sustained high blood levels of Ca
2
1
, a condition
known as
hypercalcemia
(hi
0
per-kal-se
9
me-ah), can lead to un-
desirable deposits of calcium salts in the blood vessels, kidneys,
and other soF organs, which may hamper their function.
Other hormones are also involved in modifying bone density
and bone turnover. ±or example,
leptin
, a hormone released by
adipose tissue, plays a role in regulating bone density. Best known
for its effects on weight and energy balance (see pp. 940–941), in
animal studies leptin appears to inhibit osteoblasts. It does so
Osteoclasts
degrade bone
matrix and release
Ca
2+
into blood.
Parathyroid
glands
Thyroid
gland
Parathyroid
glands release
parathyroid
hormone (PTH).
Stimulus
Falling blood
Ca
2+
levels
PTH
Calcium homeostasis of blood: 9–11 mg/100 ml
BALANCE
BALANCE
IMB
ALANCE
IMBALANCE
Figure 6.12
Parathyroid hormone (PTH) control of blood calcium levels.
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