Unless a significant metabolic insult occurs to bone early in life, the peak adult bone mass will exceed the threshold for spontaneous fracture. Noninvasive techniques to measure bone density have provided a useful definition of osteoporosis: a mass-per-unit volume of normally mineralized bone that falls below a population-defined threshold for spontaneous fracture. While such bone mineral density assessments do not entirely account for a complete assessment of fracture risk, they do indicate that significant osteoporosis can develop only if there is a net loss of bone mass; in other words, an uncoupling of the balance between bone formation and bone resorption processes.
If net bone resorption exceeds net bone formation, bone mass declines with time (see Plate 2-30). Under these conditions, with a rapid rate of bone turnover, the decrease of bone mass is rapid. Conversely, with a slow rate of bone turnover, the decline in mass is correspondingly slow. Similarly, if net bone formation exceeds net bone resorption (as in normal bone growth and even after longitudinal growth ceases), bone mass increases with time.
Some possible combinations of bone formation/resorption are shown in the table in the upper half of Plate 2-30 and graphically presented in the lower half. Example 8 represents normal bone turnover: bone formation and bone resorption are appropriately coupled, leading to a stable bone mass with no net change (black bar on middle line). Example 4 represents greatly increased bone turnover rate, but again because formation and resorption are appropriately coupled there is no net change in bone mass. This state of bone remodeling is seen in the active stage of Paget disease (see Section 3, Metabolic Diseases, Plates 3-44 to 3-46).
Example 11 shows decreased bone turnover rate, but here, too, bone formation and resorption are appropriately coupled, with no net change in bone mass. This state of bone remodeling might be seen in the inactive phase of normal bone turnover (see example 8), or it might reflect a decrease in appropriately coupled bone remodeling that represents a normal variation.
Increased Bone Turnover. Example 1 depicts a state of severe uncoupling (decreased bone formation and increased bone resorption), which causes a net decline in bone mass over time. Such an imbalance in formation and resorption occurs in chronic glucocorticoid excess, which may be endogenous (Cushing syndrome) or iatrogenic (see Section 3, Metabolic Diseases, Plate 3-26).
Example 2 illustrates increased bone turnover rate with a normal rate of bone formation but an increased rate of bone resorption. To use the bank analogy illustrated in Plate 2-31: with time, net withdrawal from the bone bank exceeds net deposition, resulting in a decreased skeletal reserve (bone mass). This state is represented in the lower half of Plate 2-30 by the black bar below the zero line and by the red dot above the green column, indicating resultant osteoporosis. (An example of this situation is the rapid increase in bone resorption that occurs after menopause.)
In example 3, both bone formation and resorption are increased but the rate of resorption is greater than the rate of formation. Thus, there is a net loss of bone mass over a period of time, which leads to osteoporosis. Mild hyperthyroidism, mild hyperparathyroidism, and a chronic dietary calcium deficiency can cause increased bone turnover, with resorption exceeding formation. In severe hyperthyroidism and hyperparathyroidism, remodeling rates can be even greater than those shown in example 3, with a correspondingly greater difference between formation and resorption and often a greater net loss of bone mass.
Example 5 illustrates a state of increased bone formation and resorption, with formation exceeding resorption. In this circumstance, bone mass increases with time. Such a generalized state of remodeling does not occur naturally in the adult skeleton, but it can occur when once-daily PTH injection is administered to osteoporosis patients, a treatment now referred to as intermittent PTH therapy. In a pathologic context, a localized (focal) phenomenon of increased bone formation and resorption with formation exceeding resorption occurs in the osteoblastic stage of Paget disease.
< div class='tao-gold-member'>