C h a p t e r 4 4
Disorders of the Skeletal System: Metabolic and Rheumatic Disorders
1115
bone resorption by inhibiting osteoclast activity. The
most dramatic impact has been in the reduction of
multiple spine fractures, showing that treatment can
decrease progression of the disease. These drugs are
effective in men as well women and for various causes
of osteoporosis.
24
Raloxifene, a selective estrogen receptor modula-
tor (SERM) that acts only on specific estrogen recep-
tors, has been approved for prevention and treatment
of osteoporosis in postmenopausal women. Although
hormone therapy (i.e., estrogen with or without proges-
terone) has been shown to slightly reduce the risk of hip
and vertebral fractures in postmenopausal women, the
use of hormone therapy has come under scrutiny after
the release of data from the Women’s Health Initiative,
which linked hormone replacement therapy to an
increased risk of stroke, venous thromboembolism,
coronary heart disease, and breast cancer.
25
Raloxifene
does not prevent hot flashes associated with menopause
and it imposes the same risk of venous thrombosis as
estrogen.
24
Calcitonin is an endogenous peptide that partially
inhibits osteoclastic activity. Nasal calcitonin has been
approved for the treatment of postmenopausal osteo-
porosis. It has been shown to decrease the occurrence
of vertebral fractures, but not nonvertebral or hip frac-
tures. Because more effective drugs are available, it is not
usually considered first-line treatment for osteoporosis.
Teriparatide, a recombinant human parathyroid hor-
mone, stimulates bone remodeling by increasing osteo-
blast-mediated bone formation. Unlike the fluoride,
this bone appears structurally normal and is associated
with substantial reduction in the incidence of fractures.
Teriparatide is given by injection and is approved for
only 2 years of use.
24
Denosumab, the RANKL inhibitor, has recently been
approved for treatment of postmenopausal osteoporo-
sis.
24
It is given subcutaneously every 6 months. Like the
biphosphonates it suppresses bone resorption and sec-
ondary bone formation. Denosumab reduces the risk of
both vertebral and nonvertebral fractures with compa-
rable effectiveness to the potent biphosphonates.
24
To reduce their fracture risk, persons with osteopo-
rosis should correct conditions in their homes that pre-
dispose them to falls. They should follow their health
care provider’s prescribed diet and program of physical
activity. In treating fractures, it is important to minimize
immobility. Surgical interventions are used to provide
stable fixation of lower extremity fractures and allow
for early weight bearing and restoration of mobility and
function. Vertebral fractures are treated symptomati-
cally. Conservative treatment with bracing is most often
seen, especially in fractures of the thoracic vertebra.
Osteomalacia and Rickets
In contrast to osteoporosis, which causes a loss of total
bone mass and results in brittle bones, osteomalacia and
rickets produce a softening of the bones resulting from
an inadequate mineralization of newly formed bone
matrix.
4
The term
rickets
refers to the disorder in chil-
dren in which changes in bone growth produce charac-
teristic skeletal abnormalities, and
osteomalacia
is used
in adults because the bone that forms during the remod-
eling process is undermineralized.
4
Osteomalacia
Osteomalacia is a generalized bone condition in which
there is inadequate mineralization of bone.
3,4,15
There
are two main causes of osteomalacia: (1) insufficient
calcium absorption from the intestine because of a lack
of dietary calcium or a deficiency of or resistance to the
action of vitamin D and (2) phosphate deficiency caused
by increased renal losses or decreased intestinal absorp-
tion. Vitamin D is ingested in the diet and synthesized
in the skin from 7-dehydrocholesterol under the influ-
ence of ultraviolet B (UVB) sunlight. The vitamin is first
hydroxylated in the liver to form its major metabolite,
25-hydroxyvitamin D. It is then hydroxylated in the
kidney to produce the active hormone 1,25(OH)
2
D
(see Chapter 42). There are many causes of vitamin D
deficiency including reduced skin synthesis, inadequate
dietary intake, diminished intestinal absorption, and
heritable and acquired disorders of vitamin D metabo-
lism and responsiveness.
26,27
The incidence of osteomalacia is high among the
elderly because of diets deficient in calcium and vita-
min D, a problem often compounded by the intestinal
malabsorption that accompanies aging. Melanin is
extremely efficient in absorbing UVB radiation; thus,
decreased skin pigmentation markedly reduces vitamin
D synthesis, as does the use of sunscreens. Osteomalacia
also may occur in persons on long-term treatment with
medications such as anticonvulsants (e.g., phenytoin,
carbamazepine, valproate) that decrease the activation
of vitamin D in the liver. There also is a greater inci-
dence of osteomalacia in the colder regions of the world,
particularly during the winter months when UVB radia-
tion is inadequate to allow skin synthesis of vitamin D.
A form of osteomalacia called
renal rickets
occurs in
persons with chronic renal failure. It is caused by the
inability of the kidney to activate vitamin D and excrete
phosphate and is accompanied by hyperparathyroidism,
increased bone turnover, and increased bone resorption
(see Chapter 26). Another form of osteomalacia results
from renal tubular defects that cause excessive phos-
phate losses. This form of osteomalacia is commonly
referred to as
vitamin D–resistant rickets,
and often is
a familial disorder.
4
It is inherited as an X-linked domi-
nant gene passed by mothers to one half of their chil-
dren and by fathers to their daughters only. This form
of osteomalacia affects boys more severely than girls.
Long-standing primary hyperparathyroidism causes
increased calcium resorption from bone and hypophos-
phatemia, which can lead to rickets in children and
osteomalacia in adults.
The clinical manifestations of osteomalacia are bone
pain, tenderness, and fractures as the disease progresses.
In severe cases, muscle weakness often is an early
sign. Osteomalacia predisposes a person to pathologic
