General
considerations
Osteoporosis is a disease of diverse etiology that
cause a reduction in the mass of bone per unit volume. The reduction in mass is
not accompanied by a significant decrease in the ratio of the mineral to theorganic
phase, nor by any known abnormality in bone mineral or organic matrix.
Histologically, the disorder is characterized by a decrease in cortical thickness
and in number and size of the trabeculae of cancellous bone. Individual trabecular
connectivity is reduced.
The osteoid seams, however, are of normal width.
Osteoporosis is the most common of the metabolic bone disease (disorders in which
all the skeleton is involved) and is an important cause of morbidity in the elderly.
Pathogenesis
The
remodeling of bone (its formation and resorption) is a continuous process. In
osteoporosis, the bone mass is decrease, indicating that the rate of bone resorption
must exceed that of bone formation.
Bone formation is higher in cortical
than in cancellous bone. This differences is exaggerated further in patients with
osteoporosis because because rates of formation of cancellous bone tend to be
lower in patients with osteoporosis.
Particular in women after the menopause.
The fact that about a third of postmenopausal women have high skeletal turnover,
assessed by whole-body retention of tc-methylene diphosphonate and by other biochemical
markers, could reflect the greater relative contribution of cortical remodeling
in this group.
After closure of epiphyses and cessation of longitudinal
growth, there is a period of consolidation with a decrease in cortical porosity.
When peak adult bone mass is reached at about age 30 to35 for cortical bone and
probably earlier for trabecular bone, rates of bone formation and resorption are
relatively low(compared with the period of growth spurt) and approximately equal.
The normal balance between bone formation and resorption result in maintaince
of skeletal mass. The rates of remodeling differ, however, not only in cortical
compared with trabecular bone but also in individual bones or portions of bones.
Most of the bone surfaces are “inactive” and not involved at any
given time either in formation or resorption. Active surface may be distributed
randomly, but formation or resorptions are locally coupled as units.
Resorption areas are covered by osteoclasts in active: bone formation surfaces
are characterized by the presence of osteoid seams and are covered by active osteoblasters.
Resorption precedes formation and is probably more intense, but it does not last
as long formation.
As a consequence, there are normally more sites of
active formation than of resorption. Bone turnover is high when there are many
units active and low when there are few.
Unless formation compensates
for resorption, bone mass decreases. In both sexes after age 40 to 50 there is
a slow rate of loss cortical bone of about 0.3 to 0.5 percent per year. In women
around the menopause, an accelerated loss of cortical bone is superimposed on
the age-related loss.
Loss of trabecular bone begins at an earlier age in both sexes but is probably
greater in degree in women. The rate of bone loss in women also may be accelerated
around the time of menopause.
The cumulative losses of bone mass range
from 20 to 30 percent in men and 40 to 50 percent for some women. In general,
the bone loss involves predominantly trabecular bone in the spine and distal radius
in women and the spine and hip in both women and men.
The fact that
loss is not uniform has been documented with techniques such as single and dual-photon
absorptiometery, quantitative computed tomography, x-ray-based dual-energy densitometry,
and neutron activation analysis of total body calcium.
For example, the
rate of loss is greater in the metacarpals, the femoral neck, and the vertebral
bodies than in the airshaft of the femur, the tibia, and the skull.
Although,
as noted, skeletal turnover may be increased, turnover is usually normal or low.
Bone formation is low in the majority, but the degree of reduction varies with
the different bone surface.
The major remodeling abnormalities in patients
with vertebral crush fractures are a reduced frequency of activation of remodeling
units and a decrease in the function of osteoblasts.
Even in those individuals
with increased bone resorption, however, bone formation does not compensate. At
some critical point if the difference between rate of formation and resorption
is maintained, loss of bone substance may become so marked that the bone can no
longer resist the normal mechanical forces to which it is subjected, and fracture
results.
This problem is most evident following perforation of bony
trabecular plates. The template for formation of new bone is lost, and loss of
bone is rapid as bone resorption continues and is even more uncoupled from resorption.
Osteoporosis usually becomes a clinical problem following fracture.
Although the level of reduction in bone mass sufficient to result in fracture
after minimal trauma is variable, the bone mineral density as measured by x-ray-based
dual-energy absorptiometery (DEXA) is an excellent predictor of fracture risk.
The strength of bone such as vertebrae depends on “quality”
as well as mineral density.The age-related loss of bone begins earlier and proceeds
more rapidly in women, and there is a trend toward acceleration of bone loss before
the menopause.
All the reasons for this age-associated bone loss are
not known, although several risk factors have been identified. In general, white
women have a greater risk than black women. , and white men have a greater risk
than black men.
One explanation for these population difference is that
the bone mass at skeletal maturity is one determinant of the bone man at subsequent
ages.
The
lower incidence of osteoporosis and hip fracture in back men and women has been
attributed to a higher bone mineral content in blacks than in whites despite the
fact that bone formation is lower in blacks.
Since formation and resorption
are usually coupled, and since bone mass is increased, bone resorption (and turnover)
also must to reduced. Osteoporotic subjects are frequently less muscular and have
lower average body weight.
Patients
who are kept at complete bed rest and astronauts in microgravity can lose approximately
I percent of their bone mass month. Exercise may have a beneficial effect in maintaining
bone mass.
The
fact that accelerated bone loss accompanies the menopause in some women and that
premature osteoporosis occurs after premature surgical menopause suggests that
estrogens play a major role in preventing bone loss.
Furthermore, Osteoporotic women as a group may have an earlier menopause than
age-matched nonosteoporotic women. Osteoporotic women also have a higher incidence
of smoking; cigarette smoking might directly affect bone remodeling or have secondary
effects on ovarian function.
Excessive alcohol consumption, which can
result in decreased bone formation, also is a risk factor for osteoporosis. Dietary
calcium intake during the first three decades of life influences the ultimate
peak bone mass.
Calcium
intake during adult life has a small effect on bone mass and risk of fracture.
Inability to synthesize adequate amounts of 1 A ( Alfa), 25-dihydroxyvitamin D
( 1,25[OH]2 D) may play a rile in the decreased calcium absorption, possibly because
of decreased sensitivity of the 25(OH)D-1 ALFA- hydroxylase to parathyroid hormone
or impaired activity of the renal 25(OH)D-1 ALFA- hydroxylase.
| Investigation,
diagnosis and treatment of Osteoporosis | Various
symptoms and other risk factors associated with the Osteoporosis |
