DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1286
Bone lining cells
Bone
Osteoclasts
SECTION V
HORMONES AND HORMONE ANTAGONISTS
Osteoblasts
rebuilding
Osteoblasts
induction
Resorption by
osteoclasts
Figure 44–8. The bone remodeling cycle. Osteoclast precursors fuse and are activated to resorb a lacuna in a previously quiescent surface.
These cells are replaced by osteoblasts that deposit new bone to restore the integrity of the tissue. (Adapted with permission from
Skerry TM, Gowen M. Bone cells and bone in remodelling in rheumatoid arthritis. In: Mechanisms and Models in Rheumatoid
Arthritis [Henderson B, Edwards JCW, Pettipher ER, eds.], Academic Press, London, 1995, pp. 205–220.)
newly formed osteoid reaches a thickness of ~20 μm, mineralization
begins. A complete remodeling cycle normally requires ~6 months.
If the replacement of resorbed bone precisely matched the
amount that was removed, remodeling would not change net bone
mass. However, small bone deficits persist on completion of each
cycle, reflecting inefficient remodeling dynamics. Consequently, lifelong
accumulation of remodeling deficits underlies the well-documented
phenomenon of age-related bone loss, a process that begins
shortly after growth stops. Alterations in remodeling activity represent
the final pathway through which diverse stimuli, such as dietary sufficiency,
exercise, hormones, and drugs, affect bone balance. Changes
in the hormonal milieu often lead to an increase in the activation of
remodeling units. Examples include hyperthyroidism, hyperparathyroidism,
and hypervitaminosis D. Other factors that may impair
osteoblast function include high doses of corticosteroids or ethanol.
Finally, estrogen deficiency augments osteoclastic resorptive capacity
by a proapoptotic action (Manolagas et al., 2002).
At any given time, a transient deficit in bone, the remodeling
space, represents sites of bone resorption that have not yet filled in.
Stimuli that alter the rate of emergence of new remodeling units
either increase or decrease the remodeling space until a new steady
state is established at an increased or decreased bone mass.
DISORDERS OF MINERAL HOMEOSTASIS
AND BONE
Abnormal Calcium Metabolism
Hypercalcemia. Moderate elevations of the concentration
of Ca 2+ in the extracellular fluid may have no clinically
detectable effects. The degree of hypercalcemia and the
rate of onset of the elevation in the serum calcium concentration
largely dictate the extent of symptoms.