- Discussion:
- generalized pathologic processes in bone can be best understood by understanding how these processes
alter the normal sequence of bone
remodeling as described in the previous chapter;
- bone remodeling occurs in local groups of
osteoblasts and
osteoclasts called bone multicellular units (BMU);
- each unit is organized into "cutting cone" of osteoclasts reabsorbing bone followed
by trail of osteoblasts reforming the bone to fill defect left by osteoclasts;
- end product is a new osteon;
- each BMU has a finite lifetime, so new units are continuously forming as old units are finishing;
- in normal bone, number of BMUs, bone
resorption rate, and bone formation rate are all relatively constant;
- for this reason a steady-state situation develops such that the total amount of bone "missing" due to bone
remodeling at any one time is fairly constant;
- any changes in the number of BMUs, resorption rate, or formation rate will alter this steady-state situation;
- in adult, bone removed by a BMU is not 100% restored, & small amount of bone is permanently lost;
- this gradual bone loss (failure to completely reform bone within each BMU) is a normal phenomenon
in humans and accounts for gradual loss of bone with age;
- pathologic conditions in bone may increase the amount of irreversible bone loss by either increasing
the total number of BMUs or by increasing the amount of irreversible bone loss in each BMU;
- increases in irreversible bone loss per BMU can result from:
- overactivity of
osteoclasts so that more bone is resorbed
than "normal"
osteoblasts can replace;
- decreased capacity of osteoblasts to reform "missing" bone although resorption may be normal;
- irreversible bone loss occurs both in cortical & trabecular bone;
- theoretically, all cortical bone resorbed could be replaced by osteoblasts, and in trabecular bone >
100% of bone removed could be replaced by decreasing marrow "space;"
- however, in nl adult, this degree of replacement does not occur;
- if greater bone formation than bone
resorption could be induced, the
treatment of osteopenic bone conditions would be greatly enhanced;
- permanent increase in bone mass does not normally occur in adult, except possibly in instances
of periosteal bone formation owing to exercise;
- leading cause of metabolic bone disease is increase in number of BMUs;
- there are many different types of stimuli that lead to this increase, best studied being parathyroid hormone;
- in mild hyperparathyroidism the number of BMUs is increased, but rates of bone resorption
and formation in each BMU are unaffected and remain well matched;
- amount of irreversible bone loss is, therefore, relatively small;
- in some situations, such as severe hyperparathyroidism, increase in total bone
resorption
can be so great that bone formation cannot keep pace, and large quantities of bone can be lost;
- metabolic bone diseases characterized by an increase in the amount of irreversible bone loss within
each BMU can be produced by alteration in rate of bone
resorption, rate of bone formation, or both;
- mismatch between the rates of formation and reabsorption is critical factor leading to bone loss;
- in high turnover osteopenia both rates are increased;
- formation simply does not keep pace with resorption;
- most patients with postmenopausal
osteoporosis have a low turnover osteopenia;
- in this situation, rate of
resorption is generally unchanged, but for unknown reasons, the
rate of formation is decreased;
- Biopsy:
- there are many possible combinations of abnormalities in bone-
remodeling dynamics that could
cause changes in total bone mass;
- to understand or treat metabolic bone diseases, it is important to determine which abnormalities in
the BMU are present;
- this is best done by histomorphometric analysis of a bone biopsy after labeling of the bone w/
tetracycline, which serves as a dated fluorescent marker;
- this technique permits quantification of rates of bone formation,
resorption, and number of BMUs;
