For many decades, scientific studies and writings about the cells that govern bone health have focused on two types of cells: osteoblasts and osteoclasts. But it turns out that a third type of cell, long overlooked and underestimated, might be the most important regulator of bone remodeling.

Today, we’ll highlight this often-overlooked bone cell. You’ll gain a thorough understanding of how it manages the strength and quality of your bones, along with its surprising role in other bodily systems.

Then we’ll look at a review of scientific studies that offer you concrete steps for improving the bone-building ability of these powerful cells.

A Mystery Of Bone Biology Solved

Osteocytes constitute 90 to 95 percent of all bone cells, making them the most prevalent type. In spite of their ubiquity, they have received relatively little attention and scientific study compared to osteoclasts and osteoblasts.

Osteoclasts are the cells responsible for resorbing old or damaged bone mass. Osteoblasts create and deposit new bone mass. These two easy-to-observe actions have dominated the study of bone health and our understanding of the mechanics of bone loss and osteoporosis.

However, several questions remained unanswered. How do osteoblasts and osteoclasts communicate? How do they know how much bone to resorb or build? We can see that bone adapts to use, as stated in Wolff’s Law— the more you use the muscles connected to a bone, the more mass that bone will add. But how do bones sense when muscles are used?

Over the past decade the consensus among scientists points to osteocytes as the answer to these questions.^1,2

Synopsis

Osteocytes are the most common type of bone cell, but their function was unknown for decades. Meanwhile, questions about how the body regulates bone remodeling persisted. Recent research suggests that osteocytes are responsible for regulating the cells that carry out bone remodeling.

Osteocytes Are At The Center Of Bone Regulation

Until recently, scientists thought that osteocytes were merely a passive placeholder in the structure of bone. Unlike short-lived osteoblasts and osteoclasts, osteocytes live for years or even decades.

Osteocytes are spread throughout bone, in small cavities known as lacunae. They have tentacle-like dendrites that reach out and connect with the surface of bone, other cells, and even blood vessels.

All of these observable traits turned out to be clues to the function of these cells. Their even distribution and interconnectedness make them well-positioned for their primary task: monitoring the condition of bones and regulating bone formation locally and systemically.³

The mechanisms by which osteocytes accomplish this task went unnoticed for many decades. However, studies have now revealed that osteocytes sense mechanical pressure placed on bones and receive hormonal messages about bone quality.¹

In response, osteocytes produce and release compounds that prompt the development and action of osteoblasts, the cells that build new bone, and osteoclasts, the cells that resorb old or damaged bone.

They can either send these chemical signals directly to other cells, or release them into the extracellular fluid prompting the generation and activation of osteoblasts and osteoclasts.

They can even release compounds into the bloodstream to send instructions to distant organs.³ This multiplicity of functions is unusual for a single cell, which typically has a more limited range of actions. Osteocytes are truly unique and powerful cells.

Synopsis

Osteocytes have recently been discovered to serve multiple major functions in bone and bodily systems. They monitor the condition of bones and regulate bone formation through the release of compounds that stimulate the generation and action of osteoblasts and osteoclasts, the cells responsible for creating and resorbing bone mass.

Osteocytes Gather Information And Give Instructions

Osteocytes, spread throughout mineralized bone, have the unique ability to detect mechanical pressure exerted on bone, making them mechanosensitive. That pressure is most often the result of the force applied to bones by muscles.

Every movement we make requires muscles to contract, pulling on the bone. Osteocytes sense this mechanical loading, and they respond to it by releasing compounds called paracrine factors. These factors activate the bone remodeling process, ultimately resulting in the addition of bone mass to locations where bones are in use.

This is the mechanism behind Wolff’s Law, which observes that bones adapt to use by adding mass. This principle also explains why exercise is so important for building bone

Osteocytes also react to hormonal information from other bone cells about the condition of those cells, such as damage and cell death. Osteocytes use that information to direct the production of osteoclasts to remove damaged or dead bone cells, and osteoblasts to replace them with healthy new bone mass.

Additionally, osteocytes release compounds instructing the kidneys on phosphate release. In this regard, they function as endocrine cells, producing factors that regulate phosphate transport.³ Phosphate is a major building block of the bone mineral matrix. It combines with calcium to form hydroxyapatite crystals that strengthen bone.

Synopsis

Osteocytes can sense mechanical pressure on bones and receive information from hormones about the condition of bone cells. They respond to this mechanical and hormonal information by releasing paracrine factors that generate and activate osteoblasts and osteoclasts. They also communicate with the kidneys to regulate the release of phosphate to be used for the production of new bone mineral matrix.

How Osteocytes Regulate Bone Remodeling

Osteocytes regulate the bone remodeling cycle through the release of many different factors and compounds. They include:³

• Dentin matrix protein 1 (DMP1)
• Phosphate-regulating neutral endopeptidase on chromosome X (PHEX)
• Matrix extracellular phosphoglycoprotein (MEPE)
• Sclerostin
• Fibroblast growth factor 23 (FGF-23)
• Osteoprotegerin (OPG)
• Receptor activator of nuclear factor-κB ligand (RANKL)

Savers are likely to recognize some of these factors. Several of them are targets of osteoporosis drugs that artificially intervene in the regulation of the bone remodeling process.

For example, the osteoporosis drug Prolia (denosumab) works by mimicking osteoprotegerin to inhibit RANKL and ultimately render osteoclasts inactive. The drug Evenity (romosozumab) inhibits sclerostin, a compound that limits bone formation. By inhibiting sclerostin, Evenity alters the instructions given by osteocytes, which leads to increased bone formation.

However, these pharmaceutical interventions have many negative side effects and are only temporarily able to overpower the body's natural bone remodeling system. At best, the result is a short period of more dense but less healthy bones.

As Savers know, bone mineral density is not the only or even the most important measure of bone health and fracture risk.

Synopsis

Osteocytes generate the factors involved in bone formation and resorption. These same factors are imitated by drugs that artificially intervene in the regulation of the bone remodeling process to increase bone mineral density.

How To Improve Osteocyte Function

As we age, more osteocytes die than are created, and osteocyte function diminishes. This is an underlying cause of imbalances in bone remodeling, leading to bone loss and osteoporosis.⁴

However, studies have found that regular weight-bearing physical activity has a strong positive effect on bone health through the activation of osteocytes.⁵ This activation of osteocytes is essential for their function, and we can be triggered with exercise.

Many studies have proven the positive end results of regular exercise, including increasing strength, building bone, and preventing falls.⁶ Now we understand more about how that cause and effect passes through osteocytes.

Synopsis

Osteocyte number and function diminish with age, but studies have found that regular weight-bearing physical activity activates osteocytes and has a positive impact on bone health.

What This Means To You

Activate your osteocytes through consistent weight-bearing exercise. These powerful cells are in charge of receiving information about what your body needs. Exercise tells your osteocytes that you need strong and durable bones. You can access all the support you need to build your ideal workout routine through SaveTrainer.

The Save Institute specially designed SaveTrainer to be adaptable to your needs. Professional trainers lead you through exercises and activities at your ability level, and a wide variety of disciplines and workouts are available, from yoga to strength training, to meditation classes. Take advantage of what SaveTrainer has to offer today.

Upcoming research might unveil even more fascinating information about the abilities of osteocytes. As you keep learning, you’ll continue to apply your newfound knowledge to live the healthiest and fullest life possible.

References

¹ https://www.annualreviews.org/doi/full/10.1146/annurev-physiol-021119-034332

² https://rmdopen.bmj.com/content/1/Suppl_1/e000049

³ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366431/#:~:text=They%20produce%20the%20soluble%20factors,kidney%20to%20regulate%20phosphate%20transport

⁴ https://www.nature.com/articles/s41419-020-03059-8

⁵ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705732/

⁶ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812467/