The Wisdom of Our Bones: How Osteocalcin Shapes Stress, Regulation, and Relationships

 
 

By Kim Barthel

At Relationship Matters, we often explore the complex interplay between body, brain, and behaviour in the context of healing, connection, and regulation. One surprising player in this dynamic system is a hormone produced not by the brain or glands, but by the bones themselves. Osteocalcin is a bone-derived hormone with powerful effects on the nervous system, metabolism, and stress response, key elements that shape our capacity to be present in relationship.

Traditionally, we think of bones as structural support, rigid frameworks for muscles and joints. But the skeleton is alive and dynamic, producing not just blood cells and minerals, but also hormonal signals that reach far beyond the bone. Osteocalcin, released by osteoblasts (bone-building cells), is now understood as a messenger molecule that speaks to the brain, the adrenal glands, and even the heart.

This recognition opens the door to a new paradigm: our bones are involved in regulating how we feel, how we cope, and how we relate.

When we experience stress, whether physical, cognitive or emotional/relational, our autonomic nervous system (ANS) plays a role. It’s the system responsible for the body’s automatic responses, including the familiar sympathetic (fight-or-flight) and parasympathetic (rest-and-digest) branches.

Osteocalcin plays a key role in activating the sympathetic nervous system. It’s released rapidly during stress and stimulates the adrenal glands to release adrenaline and noradrenaline—mobilizing energy, heightening alertness, and supporting quick action. Interestingly, this happens independently of cortisol, the slower stress hormone that’s often associated with overwhelm or shutdown.

Osteocalcin supports a fast, flexible stress response, and because it interacts with the brain as well, it influences how we perceive threat and make decisions in real time.

The Brain-Bone Connection:

Osteocalcin crosses the blood-brain barrier and binds to receptors in the brainstem and hypothalamus - regions involved in autonomic regulation, emotional tone, and motivation. It enhances learning and memory, sharpens attention, and helps the brain evaluate novelty and uncertainty. Think about how this concept of movement relates to learning in the classroom.

From a trauma-sensitive perspective, this is remarkable. It means that bone-based signals help shape our neurophysiological state, including how we orient to others, manage arousal, and stay in relational connection.

Like fascia, connective tissue, and the vagus nerve, bone is part of the body’s deep listening system - receiving cues from the environment and responding in ways that protect, adapt, and regulate. The hormone osteocalcin is one example of how interoceptive awareness may be rooted not only in the brain or gut, but also in the living intelligence of the skeletal system.

From this lens, supporting healthy bone function is also a relational intervention. Movement, weight-bearing activity, and balanced nutrition all contribute to osteocalcin signaling, and therefore to our stress resilience and relational presence.

Whether we’re working with individuals on the spectrum, supporting caregivers, or offering trauma-sensitive intervention, understanding the science of regulation matters. In the dance of connection, the wisdom in our bones is always part of the rhythm. And the more we understand this, the more we can invite it into our healing relationships.

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For reference: For more information on how biology and science informs clinical practice, the following learning opportunities are available:

References

Elefteriou, F., Campbell, P., & Ma, Y. (2014). Control of bone remodeling by the peripheral sympathetic nervous system. Calcified Tissue International, 94(1), 140-151.

Karsenty, G., & Oury, F. (2014). Regulation of male fertility by the bone-derived hormone osteocalcin. Molecular and Cellular Endocrinology, 382(1), 521–526. https://doi.org/10.1016/j.mce.2013.08.013

Khrimian, L., Obri, A., Ramos-Brossier, M., Rousseaud, A., Moriceau, S., Nicot, A. S., … & Karsenty, G.(2017). Gpr158 mediates osteocalcin’s regulation of cognition. Journal of Experimental Medicine, 214(10), 2859–2873. https://doi.org/10.1084/jem.20171320

Ma, C., Zhang, Y., Cao, Y., Hu, C. H., Zheng, C. X., Jin, Y., & Sui, B. D. (2024). Autonomic neural regulation in mediating the brain–bone axis: Mechanisms and implications for regeneration under psychological stress. QJM: An International Journal of Medicine, 117(2), 95-108.

Mera, P., Laue, K., Ferron, M., Confavreux, C., Wei, J., Galán-Diez, M., … & Karsenty, G. (2016). Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise. Cell Metabolism, 23(6), 1078–1092. https://doi.org/10.1016/j.cmet.2016.04.004

Oury, F., Khrimian, L., Denny, C. A., Gardin, A., Chamouni, A., Goeden, N., … & Karsenty, G. (2013). Maternal and offspring pools of osteocalcin influence brain development and functions. Cell, 155(1), 228–241. https://doi.org/10.1016/j.cell.2013.08.042

 
 
 
 
 
 
 
Kim Barthel