20.4: Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.

Hormonal Control of Bone Remodeling

Parathyroid hormone (PTH) maintains homeostatic control of blood calcium levels by regulating bone resorption. PTH is released from the parathyroid glands in response to low levels of calcium in the blood. It stimulates osteoblasts to produce immune molecules that promote the differentiation of precursor cells into osteoclasts. Activation of osteoclasts promotes bone resorption, causing the mineralized bone matrix to break down and release calcium into the blood. When blood calcium levels are restored, a negative-feedback loop prevents further release of PTH.

Osteoporosis

Osteoporosis is a disease in which bone resorption exceeds bone formation, resulting in reduced bone density. Osteoporosis is more prevalent in women, especially after menopause. This is due to the critical role played by the female sex hormone—estrogen—in bone remodeling. Estrogen limits the formation of osteoclasts and promotes their destruction via apoptosis. This ensures that bone formation is higher than bone resorption. However, estrogen levels decline severely in menopausal women. Therefore, bone resorption outpaces its creation, leading to a loss of bone strength and increased risk of fractures.

Even in the adult skeleton bones are active tissues, continuously undergoing changes in architecture. This process called bone remodeling, consists of equal phases of bone resorption, its removal, and depositing new tissue.

When mature bone cells, osteocytes, sense mechanical stress, they signal cells to the bone site, for instance, the ends of the femur, which are replaced every six months.

During resorption, one cell type, osteoclasts, cling tightly to the surface. By secreting lysosomal enzymes and hydrogen protons, they can degrade the organic components, creating erosion cavities as they digest the old or damaged matrix. Calcium is also released into the blood and plays a role in hormonal feedback loops.

Once the material is dissolved, the osteoclast self destruct via apoptosis, which prevents further destruction of the bone. To initiate reversal, mononuclear cells appear on the surface in preparation for the next step.

In the formation phase, osteoblasts move into the cavity and deposit new bone through the ossification of organic matrix known as osteoid. This part includes collagen fibers that contribute to the structure and flexibility. After matrix synthesis, osteoblasts can differentiate into flattened bone lining cells or become buried in the bone as osteocytes.