Bone Remodeling and Repair

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone resorption and secrete several enzymes, including acid phosphatase. The acid phosphatase mineralizes the bone by degrading organic collagen and releasing calcium and phosphorus.

Bone remodeling is a skeletal change that occurs regularly in coordination with bone formation. This balances the breakdown and formation of new bone. However, after around 40 years of age, bone resorption occurs more frequently than formation, resulting in a reduction in bone density. This results in osteoporosis, which makes the bones weaker and brittle, increasing the risk of fractures.

Several hormones and proteins regulate the process of bone resorption. The Receptor activator of nuclear-factor kappa or RANK binds to its ligand and stimulates bone resorption. Calcitonin, a hormone released by the thyroid gland, reduces circulating calcium in the blood and inhibits bone resorption, thereby promoting bone formation. Similarly, parathyroid hormone or PTH increases the calcium level in the blood. Additionally, it also increases the activity of RANKL, promoting bone resorption. Growth hormone stimulates the activity of both osteoblasts and osteoclasts, thereby enabling both bone resorption and formation simultaneously.

The hormone estrogen negatively regulates bone resorption. A deficiency in estrogen increases bone resorption and bone remodeling. Calcitonin inhibits the resorption process by binding to calcitonin receptors on osteoclasts. Thus, calcitonin plays a role in calcium homeostasis and is used to treat osteoporosis.