Researchers are digging deeper into the mechanisms underlying the loss of bone that accompanies aging. A complete understanding of how imbalances occur between ongoing bone creation and destruction that takes place at the cellular level should eventually lead to ways to manipulate that process:
By analyzing biopsy specimens from patients with postmenopausal osteoporosis and primary hyperparathyroidism, investigators have begun to pay increasing attention to "reversal cells," which prepare for bone formation during bone remodeling. The hope is that these reversal cells will become critical therapeutic targets that may someday prevent osteoporosis and other bone disorders.
In adults, bones are maintained healthy by a constant remodeling of the bone matrix. This bone remodeling consists of bone resorption by osteoclasts and bone formation by osteoblasts. A failure in the delicate balance between these two processes leads to pathologies such as osteoporosis. How these two processes are coupled together is poorly understood. "Reversal cells may represent the missing link necessary to understand coupling between bone resorption and formation and to prevent osteoporosis."
Reversal cells actually cover more than 80% of the resorbed bone surfaces. Using histomorphometry and immunohistochemistry on human bone biopsies, researchers found that the reversal cells colonizing the resorbed bone surfaces are immature osteoblastic cells which gradually mature into bone forming osteoblasts during the reversal phase, and prepare the bone surface for bone formation. Researchers also found that some reversal cells display characteristics that suggest an "arrested" physiological status. These arrested reversal cells showed no physical connection with bone forming surfaces, a reduced cellular density, and a reduced expression of osteoblastic markers.
Biopsies from postmenopausal patients with osteoporosis showed a high proportion of arrested cells, but no such cells were found in biopsies from patients with primary hyperparathyroidism, in which the transition between bone resorption and formation is known to occur optimally. [Larger] arrested cell surfaces were associated with bone loss. "Our observations suggest that arrested reversal cells reflect aborted remodeling cycles which did not progress to the bone formation step. We therefore propose that bone loss in postmenopausal osteoporosis does not only result from a failure of bone formation as commonly believed, leading to incomplete filling of resorption cavities, but also from a failure at the reversal phase, uncoupling bone formation from resorption."