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The Prevention and Treatment of Osteoporosis

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Because of the aging of the population and increases over time in the incidence of fractures, these already…….. read more

OSTEOPOROSIS is one of the most important disorders associated
with aging.
1 , 2 More
than 1.5 million Americans have fractures related to osteoporosis each year,
with attendant pain, deformity, and loss of independence. The annual cost to
the U.S. health care system is at least $10 billion.
1 , 2 Because
of the aging of the population and increases over time in the incidence of
fractures, these already huge costs will more than double over the next 30
years
3 unless
a comprehensive program of prevention and treatment is initiated soon. The most
important preventable cause of fractures is low bone mass. During the course of
their lifetimes, women lose about 50 percent of their cancellous bone and 30
percent of their cortical bone, and men lose about 30 percent and 20 percent,
respectively.
1 Cancellous
bone is concentrated in the spinal column and at the ends of long bones; these
areas are the main sites of osteoporotic fractures. The tendency of the elderly
to fall, however, is an important independent cause of fractures. Although
little can be done at present to prevent such falls, important advances have
been made in methods of retarding bone loss.

Theoretical Background

ABNORMALITIES IN BONE REMODELING

Figure 1.The Bone-Remodeling Cycle at the Cellular Level.

At the cellular level, bone remodeling occurs at discrete foci in
the skeleton called bone-remodeling units. During an activation phase at the
beginning of each remodeling cycle, the cells that line bone are replaced by
osteoclasts, each of which, over a period of about two weeks, excavates a
lacuna on the surface of cancellous bone or a cavity within cortical bone (
Fig. 1). The osteoclasts are then replaced by osteoblasts that gradually
refill this space.
4


Figure 2.Scanning Electron Micrographs of Cancellous Bone in a Normal Young
Woman (Panel A) and a Postmenopausal Woman with Osteoporosis (Panel B).

The impact of this process at the tissue level is determined by
the rate of bone turnover (which depends on the total number of remodeling
units active in the skeleton, normally about 1 million) and the remodeling
balance (the relative amounts of bone resorbed and formed at each unit).
4 Bone
loss occurs when osteoclasts create an excessively deep cavity, when
osteoblasts fail to refill a normal resorption cavity, or when both occur (
Fig. 1). Both abnormalities exist in
patients with osteoporosis.
4 Increased
bone turnover by itself — for example, in a young adult with hyperthyroidism —
causes little bone loss. When bone resorption exceeds bone formation, however,
an increase in bone turnover increases bone loss, whereas a decrease in bone
turnover decreases bone loss. The imbalance between resorption and formation
caused by increased osteoclastic activity, as occurs in the immediate
postmenopausal period, is more damaging structurally than that caused by
decreased osteoblastic activity, as occurs during the slow phase of bone loss
with aging. Excessive osteoclastic activity may lead to perforation and loss of
entire trabeculae in cancellous bone, so that the subsequent formation phase is
eliminated. In contrast, decreased osteoblastic activity leads only to thinning
of the trabeculae (
Fig. 2).4 5 6

TYPES OF THERAPEUTIC REGIMENS