Bone Physiology Review

Bone Physiology Review8

The fourth learning objective of this course is to understand an overview of bone physiology and remodeling. Bone is often thought to be a static structure, but it actually is continuously remodeling through actions of osteoclasts (bone-resorbing cells) and osteoblasts (bone-building cells) and their products, under the influence of parathyroid hormone (PTH), vitamin D, estrogens, glucocorticoids, growth hormone, thyroid hormone and other factors such as cytokines, a unique family of growth factors. Remodeling is accomplished in the trabecular bone of the alveolar process, and elsewhere, by a team of cells that dissolves a pit-like area in bone and then fills it with new bone. This team of cells is called the Basic Multicellular Unit (BMU). Bone is remodeled through a sequence of steps that may take as much as 200 days, as follows:


Origination is the phase during which a BMU originates following an initiating “event” such as microdamage, mechanical stress, exposure to one or more of a group of biological factors, or even at random. The immune response begins in reaction to one of these events. Cytokines and other growth factors, such as parathyroid hormone (PTH), insulin-like growth factors (IGF), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF), are important in the Origination phase. IL-1 may be the most important factor in the immune response. Its function is to enhance the activation of T-cells in response to antigen. IL-6 is produced by fibroblasts and other cells. IL-6 enhances glucocorticoid syntheses. Overall it augments the response of immune cells to other cytokines. Tumor Necrosis Factor-α (TNF- α), like IL-1, is a major immune response-modifying cytokine produced mainly by activated macrophages. The presence of TNF induces osteoclast formation.

Factors such as estrogen can reduce occurrence of the Origination phase, thereby reducing the rate and occurrence of bone resorption. Biologically mediated strategies for improving bone growth in periodontitis patients work to modify the effects of factors that promote bone resorption or to boost the effects of the factors that promote bone growth.

Osteoclast Recruitment

The lining cells that were activated during Origination secrete RANK-ligand, which may remain bound to the cell surface. Pre-osteoclasts are activated by RANK-ligand (RANKL) and then differentiate into mature osteoclasts which develop a ruffled border and resorb bone. Osteoprotegerin (OPG) can act to bind the RANK-ligand which reduces its effect. RANK-ligand is a potent bone-building agent. Osteoclasts are more effective at resorbing bone when RANK-ligand's effect is reduced.


Bone is resorbed by the mature osteoclasts for approximately two weeks at a given location until the osteoclasts undergo pre-programmed cell death. New osteoclasts are continuously activated as the BMU travels. Integrins and interleukins are immune factors that can act to increase osteoclast activity. Integrins are cell-surface receptors that bind ligands and reduce their bone-building effect.

Estrogen, calcitonin, interferon and TGF can reduce bone resorption during this phase. Calcitonin works in opposition to parathyroid hormone and can reduce its role in bone resorption. Similarly bisphosphonates, such as risedronate sodium inhibit osteoclast mediated bone resorption thereby reducing net bone loss.

Osteoblast Recruitment

Osteoblasts are derived from bone marrow stromal cells and are attracted by bone-derived growth factors, (including Cbfa1, BMP's, IGF, PTH, and others) and perhaps the remains of the self-destructed osteoclasts. Cbfa1 activates the bone-specific protein, osteocalcin. Bone morphogenetic proteins (BMPs) induce new bone formation by stimulating profileration and migration of undifferentiated bone cell precursors.

Osteoid Formation

Osteoblasts start the process of bone-building by secreting layers of osteoid to slowly refill the cavity, as well as growth factors (including TGF-beta, BMP's and IGF) and proteins. The presence of glucocorticoids may retard osteoid formation.


The osteoid begins to mineralize utilizing calcium and phosphate when it is approximately 6 microns thick. Mineralization is controlled by osteoblast activity. The presence of pyrophosphate may reduce mineralization.

Mineral Maturation

Bone density increases over months after the cavity has been filled with bone because the mineral crystals become more closely packed.


During quiescence, some osteoblasts become lining cells which help regulate ongoing calcium release from the bones. Other osteoblasts become osteocytes which remain in bone, connected by long cell processes, which can sense functional stress on the bone.