Bones and Skeletal Tissues
is the product of the local concentrations of calcium and phos-
) ions (the Ca
product) in the endosteal cavity.
When the Ca
product reaches a certain level, tiny crystals
of hydroxyapatite form spontaneously and catalyze further
crystallization of calcium salts in the area. Other factors in-
volved are matrix proteins that bind and concentrate calcium,
and the enzyme
by the osteoblasts), which is essential for mineralization. Once
proper conditions are present, calcium salts are deposited all
at once and with great precision throughout the “matured”
As noted earlier, the giant
. Osteoclasts move along a bone surface, digging de-
pressions or grooves as they break down the bone matrix. Te
ruﬄed border of the osteoclast clings tightly to the bone, seal-
ing oﬀ the area of bone destruction and secreting
that digest the organic matrix and
resulting acidic brew in the resorption bay converts the calcium
salts into soluble forms that pass easily into solution. Osteoclasts
may also phagocytize the demineralized matrix and dead os-
teocytes. Te digested matrix end products, growth factors, and
dissolved minerals are then endocytosed, transported across the
osteoclast (by transcytosis), and released at the opposite side.
Tere they enter the interstitial ﬂuid and then the blood.
When resorption of a given area of bone is completed, the
osteoclasts undergo apoptosis. Tere is much to learn about os-
teoclast activation, but P±H and proteins secreted by ± cells of
the immune system appear to be important.
Control of Remodeling
Remodeling goes on continuously in the skeleton, regulated by
genetic factors and two control loops that serve diﬀerent “mas-
ters.” One is a negative feedback hormonal loop that maintains
homeostasis in the blood. Te other involves responses to
mechanical and gravitational forces acting on the skeleton.
Te hormonal feedback becomes much more meaningful
when you understand calcium’s importance in the body. Ionic
calcium is necessary for an amazing number of physiological
processes, including transmission of nerve impulses, muscle
contraction, blood coagulation, secretion by glands and nerve
cells, and cell division.
Te human body contains 1200–1400 g of calcium, more
than 99% present as bone minerals. Most of the remainder is
in body cells. Less than 1.5 g is present in blood, and the hor-
monal control loop normally maintains blood Ca
narrow range of 9–11 mg per dl (100 ml) of blood. Calcium is
absorbed from the intestine under the control of vitamin D me-
tabolites. Te daily dietary calcium requirement is 400–800 mg
from birth until age 10, and 1200–1500 mg from ages 11 to 24.
Te hormonal controls primarily involve
parathyroid hormone (PTH)
, produced by the parathyroid
glands. ±o a much lesser extent
duced by parafollicular cells (C cells) of the thyroid gland, may
Excesses or deﬁcits of any of these hormones can result in ab-
normal skeletal growth. For example, hypersecretion of growth
hormone in children results in excessive height (gigantism), and
deﬁcits of growth hormone or thyroid hormone produce char-
acteristic types of dwarﬁsm.
Remodeling and Repair
Compare the locations and remodeling functions of the
osteoblasts, osteocytes, and osteoclasts.
Explain how hormones and physical stress regulate bone
Describe the steps of fracture repair.
Bones appear to be the most lifeless of body organs, and may
even summon images of a graveyard. But as you have just
learned, bone is a dynamic and active tissue, and small-scale
changes in bone architecture occur continually. Every week we
recycle 5–7% of our bone mass, and as much as half a gram of
calcium may enter or leave the adult skeleton each day! Spongy
bone is replaced every three to four years; compact bone, every
ten years or so. Tis is fortunate because when bone remains in
place for long periods more of the calcium salts crystallize (see
description below) and the bone becomes more brittle—ripe
conditions for fracture.
When we break bones—the most common disorder of bone
homeostasis—they undergo a remarkable process of self-repair.
In the adult skeleton, bone deposit and bone resorption occur
at the surfaces of both the periosteum and the endosteum. ±o-
gether, the two processes constitute
ets” of adjacent osteoblasts and osteoclasts called
coordinate bone remodeling (with help from the stress-
In healthy young adults, total bone mass remains constant,
an indication that the rates of bone deposit and resorption are
essentially equal. Remodeling does not occur uniformly, how-
ever. For example, the distal part of the femur, or thigh bone,
is fully replaced every ﬁve to six months, whereas its sha² is
altered much more slowly.
—an unmineralized band of gauzy-looking
bone matrix 10–12 micrometers (μm) wide—marks areas of
new matrix deposits by osteoblasts. Between the osteoid seam
and the older mineralized bone, there is an abrupt transition
. Because the osteoid seam is always
of constant width and the change from unmineralized to min-
eralized matrix is sudden, it seems that the osteoid must mature
for about a week before it can calcify.
Te precise trigger for calciﬁcation is still controversial, but
mechanical signals are deﬁnitely involved. One critical factor