Endocannabinoid System Health Science

Role of the Endocannabinoid System in Bone

Bones provide structural support and physical protection to our soft tissues. They allow us to walk and eat and breed and carry out the activities of life. Bones are indispensable to animal biology, but where do they come from? How are they formed? What is the role of the endocannabinoid system, if any, in the formation and maintenance of the skeletal system?

What is the Skeletal System

The skeletal system, as it would seem, is comprised of our skeleton. But it’s not only composed of bone; it also includes cartilage, ligaments, and other connective tissues. Muscles are attached to bones via tendons, which pull the bone toward the muscle during contraction, thus executing movement. Bones are connected to other bones by ligaments, tough bands of fibrous tissue that give our skeleton flexibility and elasticity, preventing injury and increasing durability.

The purpose of the skeletal system is not only to provide support, but to store minerals (i.e. calcium), to produce red blood cells, to protect delicate organs, and to provide leverage for muscles to exert work. From the time that a person is born, bone is constantly broken down and rebuilt in a process called remodeling. It is estimated that about 20% of an adult’s skeleton is recycled every year.

How does the Skeletal System work?

The obvious function of the skeletal system is relatively simple: provide physical structure and support. Deceptively, bones are also entirely responsible for generating new red blood cells; about 10,000,000 of them every single day. The molecular organization of bone is highly complex and still not entirely understood, but the two processes of erythropoiesis (red blood cell formation) and bone remodelling are completely vital to a healthy and mobile organism.

Bone remodelling

Bones are home to two types of complementary cells, known as osteoclasts and osteoblasts. Osteoclasts break down old bone tissue and dissolve its constituent compounds. Osteoblasts follow close behind, absorbing much of the still-useful nutrients freed by osteoclasts, and using it to create new bone mass.

The osteoblast incorporates this matter with calcium and creates new bone tissue that is necessarily denser than the tissue it’s replacing, which was removed by osteoclasts. This process is known as bone remodeling, and it’s a vital process for the health of the entire organism. Osteoporosis results from an imbalance in the amount of bone degraded by osteoclasts relative to the new bone tissue reformed by osteoblasts.


Bone is also responsible for the formation of red blood cells. Specifically, the center core of large bones contains a substance called marrow, which is capable of producing erythrocytes. The first step in this process involves the kidneys secreting a hormone called erythropoietin (EPO), in response to decreased oxygen delivery or increased androgen activity. Once this hormone circulates to bone marrow, red blood cell production is stimulated. However, this function requires an ample supply of iron, vitamin B12, and certain other cellular substrates.

The ECS is vital in mediating both the release of erythropoietin by the kidneys and the response of bone marrow to it. It’s also heavily involved in the homeostasis of vitamins and minerals, which are also necessary for the physiological production of red blood cells.

What is the Role of the Endocannabinoid System in the Skeletal System?

Research has long described the endocannabinoid system as vital for the essential function of the nervous and immune systems, and the ECS is present in the majority of mammalian organs and tissues. However, scientific studies published in 2008 revealed that endocannabinoids and their receptors are present in bones as well.

The cells that synthesize bone – osteoblasts – have been found to produce the cannabinoids anandamide (AEA) and 2-arachidonoylglycerol, and to express CB1 receptors on their surfaces. CB1 activation in osteoblasts inhibits the release of norepinephrine, which tonically suppresses the bone formation process; i.e. CB1 activation stimulates (disinhibits) bone production.

Furthermore, osteoclasts also express AEA and 2-AG, but with CB2 receptors instead of CB1. CB2 activation in osteoclasts suppresses bone-dissolving activity, preserving bone tissue. In cases of osteoporosis, this effect could prove highly beneficial in balancing the relationship between overactive osteoclasts and underactive osteoblasts which result in increased bone resorption without compensatory bone formation.

With these recent findings, scientists believe that the primary regulatory system of the skeleton is the ECS. While norepinephrine is directly responsible for the activity of osteoclasts and osteoblasts, the levels of norepinephrine are largely mediated both by the endocannabinoid system expressed in the sympathetic nervous system, and the endocannabinoid system expressed in bone tissue itself. Indeed, the ECS “regulates regulation”.

Can endocannabinoid deficiency affect the Skeletal System?

A study conducted by I. Bab and A. Zimmer in 2008 examined the relationship between a deficiency of CB2 receptor expression and decreased bone density in 388 postmenopausal females. In the experiment, several single nucleotide polymorphisms (SNPs; mutations of a single nucleotide in a specific gene) were studied.

The study showed that more than 20 SNPs (pronounced “snips”) of the CB2R gene were associated with osteoporosis in statistical models. However, the greatest P-Values (a measure of the significance of a statistical relationship) were associated with just two specific polymorphisms, suggesting the existence of a specific phenotype of the CB2 receptor that may contribute to the development of osteoporosis (Karsak et al., 2005).

The discovery that the endocannabinoid system is implicated in bone pathology means that it’s also a potential target for treatment of various bone conditions including osteoporosis. The more we are able to ascertain about the numerous and diverse functions of the endocannabinoid system, the more we are sure to learn about many other conditions and physiological systems which depend on it.