Osteocalcin, the Hormone Believed to Protect Our Brain


Hormones are “chemical messengers that coordinate different functions in the body.” Most of us are aware of and relatively knowledgeable about a handful of them such as estrogen, testosterone, oxytocin, serotonin, melatonin and cortisone.

But did you know there is another hormone, a bone hormone called osteocalcin?

The story of osteocalcin, the hormone believed to protect our brain from age-related memory loss, anxiety, depression, and learning impairment, begins in the laboratory of a French geneticist named Gerard Karsenty. Uncelebrated and unknown at the time, he currently holds the chair position at the Dept. of Genetics and Development, Columbia University Medical Center.

Curious about the role a mysterious protein found in bone played in laying down the mineral layers that contribute to the strength of our skeletons turned out to be the stimulus that led Karsenty to the discovery of osteocalcin.

Osteocalcin –

Osteocalcin is a bone hormone produced by osteoblasts, cells that form from bone tissue and travel across the surface of bone in the wake of another cell type known as an osteoclast. Osteoclasts break down existing bone and release calcium and other minerals into the bloodstream for use by the rest of the body, while osteoblasts follow behind, working to repair the damage done and rebuilding the missing bone.

Osteoblasts, responsible for bone formation, are naturally more active than osteoclasts when we’re young, so the “bone remodeling” process results in bone growth. However, as we age, the balance of power switches and favors osteoclasts/breaking down of bone (an issue that goes into overdrive for women when menopause hits and their ovaries stop pumping estrogen into the bloodstream).

Seeking answers that revealed the biological function of osteocalcin, Karsenty bred a group of mice which lacked the gene for osteocalcin production. Mice and humans share nearly 98 percent of their genetic code, and at the level of proteins their biology is very similar. Karsenty was confident he could learn a lot about the role of osteocalcin in human bone production by studying his “osteocalcin knockout” mice (those in which the gene had been knocked out of their DNA).

To his surprise, the knockout mice showed no signs of any kind of bone impairment. If anything, their bones were even stronger. However, Karsenty did notice something odd about his osteocalcin-deficient mice. For the most part, they all seemed anxious, depressed, and fatter than normal. They were very sedentary, barely moving in their cages (explaining in part their weight gain) and when picked up by human handlers, never tried biting anyone or escaping their cage.

It seemed deleting osteocalcin from the bodies of these mice somehow affected their brains, a strange revelation since Karsenty believed osteocalcin was only generated in bone. There was only one logical explanation/conclusion; osteocalcin must have somehow traveled in the bodies of normal mice from their bones to their brain. How and why? What’s the connection?


Around the same time Karsenty was wrestling with his discovery about osteocalcin acting like a kind of brain-influencing hormone, another group of unrelated researchers isolated a completely different protein that appeared to be the master switch for the brain, called BDNF. BDNF, (short for brain-derived neurotrophic factor) is produced in the brain and responsible for several processes critical to long-term brain health.

As the master switch for our brains, BDNF increases activity that works to repair damaged neural pathways. It helps stimulate and sprout the growth of new brain cells, boosts intelligence, lightens our moods, increases productivity and strengthens memory. Brain cells in Petri dishes were visual proof of this as they grew and sprouted new branches when sprinkled with BDNF.

So, what’s the best way to rev up and turn on this mental health, growth and protective powerhouse?

Exercise! In volunteers that participated in an experimental protocol involving strenuous activity, large surges of BDNF were found flowing in their brain, proving that BDNF and exercise are intimately related. Ongoing studies continually back this up.

What’s the connection between osteocalcin that travels to the brain from the bones and BDNF that’s made in the brain?

While Karsenty was busy publishing his findings about osteocalcin, another team from the University of California, San Francisco discovered the age rejuvenating abilities of “young blood.” It seemed passing the blood plasma of young mice into older mice bodies reversed the effects of age-related cognitive decline. Memory tests were better, anxiety decreased, and the mice were no longer afraid to explore their environment. The brains of old mice functioned as if they were the brains of young mice. It was obvious, something in the blood plasma of young mice was acting like an age reverser.

Karsenty was the one that figured out that osteocalcin was produced in the bones of active mice, not sedentary ones. Experimenting with both young mice and young humans, he was able to detect a large increase (more than a doubling) the level of circulating osteocalcin after a bout of intense exercise. The proof was there, stress placed on bones by physical activity stimulates osteocalcin production. But where does BDNF come in?

Once osteocalcin is stimulated, it begins its journey through the bloodstream to the brain where it crosses the blood-brain barrier and attaches to a set of receptors in the brainstem, the midbrain and the hippocampus (our memory and learning center). This is where it becomes the signaling mechanism that stimulates BDNF to perform its duties.

It’s a powerful chain of events. With proper intense movement/exercise, our bones (via stress) release the bone hormone osteocalcin. This hormone then travels to the brain where it stimulates the production of BDNF, our mental health protector and mood booster. Without BDNF our mental state would devolve rapidly eventually rendering us an addled-brained simpleton.

The moral of the story? Weak bones, weak mind. Our mental health and muscle strength are not a given but rely heavily on healthy bones. Bones are way more than just skeletal frames that muscles attach to, holding us up and protecting our organs. They provide hidden qualities and aid bodily functions that our cognitive abilities, moods and production in life count on.

Challenging exercise/movement is the key thread that both stimulates and ties it all together.

Not surprisingly, when it comes to enjoying healthy longevity with mental clarity and physical stamina, exercise gets the nod again.

Diligent, consistent strength training workouts and a strong commitment to follow through,  produces significan positive mental, emotional and physical results.

If you truly want to take command of your emotions, your health and your life…

“Healthy Self Healing” can help you achieve this goal.

For more tools and resources from Carolyn Hansen to assist you in attaining your health and fitness goals please visit:

Carolyn Hansen Fitness

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