Bones and Skeletal Tissues
along with reduced mineralization, causes a spotty weaken-
ing of the bones. Late in the disease, osteoclast activity wanes,
but osteoblasts continue to work, oFen forming irregular bone
thickenings or ﬁlling the marrow cavity with Pagetic bone.
Paget’s disease may aﬀect any part of the skeleton, but it is
usually a localized condition. Te spine, pelvis, femur, and skull
are most oFen involved and become increasingly deformed and
painful. It rarely occurs before age 40, and it aﬀects about 3% of
North American elderly people. Its cause is unknown, but a vi-
rus may trigger it. Drug therapies include calcitonin (adminis-
tered by a nasal inhaler), and the newer bisphosphonates, which
have shown success in preventing bone breakdown.
Check Your Understanding
Which bone disorder is characterized by excessive deposit of
weak, poorly mineralized bone?
What are three measures that may help to maintain healthy
What name is given to “adult rickets”?
For answers, see Appendix H.
of Bones: Timing of Events
Describe the timing and cause of changes in bone
architecture and bone mass throughout life.
Bones are on a precise schedule from the time they form until
death. Te mesoderm germ layer gives rise to embryonic mesen-
chymal cells, which in turn produce the membranes and cartilages
that form the embryonic skeleton. Tese structures then ossify
according to an amazingly predictable timetable that allows fetal
age to be determined easily from either X rays or sonograms. Al-
though each bone has its own developmental schedule, most long
bones begin ossifying by 8 weeks aFer conception and have well-
developed primary ossiﬁcation centers by 12 weeks
Birth to Young Adulthood
At birth, most long bones of the skeleton are well ossiﬁed except
for their epiphyses. AFer birth, secondary ossiﬁcation centers
develop in a predictable sequence. Te epiphyseal plates persist
and provide for long bone growth all through childhood and the
sex hormone–mediated growth spurt at adolescence. By age 25,
nearly all bones are completely ossiﬁed and skeletal growth ceases.
Age-Related Changes in Bone
In children and adolescents, bone formation exceeds bone re-
sorption. In young adults, these processes are in balance, and
in old age, resorption predominates. Despite the environmental
factors (discussed earlier) that inﬂuence bone density, genet-
ics still plays the major role in determining how much a per-
son’s bone density will change over a lifetime. A single gene that
codes for vitamin D’s cellular docking site helps determine both
and estrogen deﬁciency is strongly implicated in osteoporosis
in older women.
Several other factors can contribute to osteoporosis:
Petite body form
Insuﬃcient exercise to stress the bones
A diet poor in calcium and protein
Abnormal vitamin D receptors
Smoking (which reduces estrogen levels)
Hormone-related conditions such as hyperthyroidism, low
blood levels of thyroid-stimulating hormone, and diabetes
Osteoporosis can develop at any age as a result of immobility.
It can also occur in males with prostate cancer who are being
treated with androgen-suppressing drugs.
Osteoporosis has traditionally been treated with calcium and vi-
tamin D supplements, weight-bearing exercise, and
). ±rustratingly, HR² slows the
loss of bone but does not reverse it. Additionally, because of the
increased risk of heart attack, stroke, and breast cancer associated
with estrogen replacement therapy, it is a controversial treatment
these days. Although not a substitute for HR², estrogenic com-
pounds in soy products (principally the isoﬂavones daidzein and
genistein) oﬀer a good addition or adjunct for some patients.
Newer drugs are available. Bisphosphonates decrease oste-
oclast activity and number, and partially reverse osteoporosis
in the spine. Selective estrogen receptor modulators (SERMs),
such as raloxifene, dubbed “estrogen light,” mimic estrogen’s
beneﬁcial bone-sparing properties without targeting the uterus
or breast. Additionally,
, drugs used to lower cholesterol
levels, have an unexpected side eﬀect of increasing bone min-
eral density up to 8% over four years. Te monoclonal antibody
signiﬁcantly reduces fractures in men ﬁghting
prostate cancer and improves bone density in the elderly.
How can osteoporosis be prevented (or at least delayed)? Te
ﬁrst requirement is to get enough calcium while your bones are
still increasing in density (bones reach their peak density during
early adulthood). Second, keep in mind that excessive intake of
carbonated beverages and alcohol leaches minerals from bone
and decreases bone density. ±inally, get plenty of weight-bearing
exercise (walking, jogging, tennis, etc.) throughout life. Tis will
increase bone mass above normal values and provide a greater
buﬀer against age-related bone loss.
OFen discovered by accident when X rays are taken for some
ets) is characterized by ex-
cessive and haphazard bone deposit and resorption. Te newly
formed bone, called
, is hastily made and has an
abnormally high ratio of spongy bone to compact bone. Tis,