Example 7 shows the highly uncoupled state of increased bone formation and decreased bone resorption that result in a net increase in bone mass. Such a state of remodeling is seen in the adult, or autosomal dominant, form of osteopetrosis (see Section 3, Metabolic Diseases, Plate 3-43). In this disorder, the reduced rate of bone resorption is due to the relative decline in osteoclastic bone resorption; the rate of bone formation may be normal or increased. This form of uncoupling may also be induced by pharmacologic doses of fluoride administered to stimulate bone formation and stabilize bone apatite crystal and render it more resistant to breakdown.

Decreased Bone Turnover. Example 9 shows a state of normal bone resorption with decreased bone formation, which leads to reduced bone mass and osteoporosis. This can occur after exposure to a poison or toxin that affects the osteoblasts, as with use of certain chemotherapeutic agents and chronic alcohol abuse.

In example 10, both bone formation and resorption are decreased but bone resorption still exceeds bone formation. This is seen when calcium and vitamin D supplementation helps to diminish age-related bone loss.

Example 13 shows a positive bone balance resulting from a normal rate of bone formation and a decreased rate of bone resorption. This occurs in women receiving replacement therapy with calcium and estrogen or calcium and calcitonin soon after menopause. These agents, administered independently or in combination, act to decrease bone resorption. The coupling process then causes bone formation rates to adjust downward accordingly (example 12); eventually, bone mass stabilizes at a much lower rate of bone remodeling (example 11). In a more extreme example, administration of bisphosphonates to patients with osteoporosis nearly eliminates bone resorption rates and, as a consequence of coupling, bone formation rates also substantially decline over treatment time.

FOUR MECHANISMS OF BONE MASS REGULATION

Plate 2-31 illustrates four basic mechanisms of bone mass regulation: (1) stimulation and (2) inhibition of bone formation, or deposition, and (3) stimulation and (4) inhibition of bone resorption, or withdrawal. However, in many cases, early changes will be checked by concomitant stimulation of the opposing bone cell population—stimulation of osteoclasts (resorption) leads to a coupled stimulation of osteoblasts (formation).