The Hip Bone’s Connected to the…Brain? Exploring the Bone-Brain Connection
- neuwritephl
- Jan 24
- 6 min read
By: Sandra Ciuciu
January 2025
The Bone-Brain Connection
At first glance, your bones and brain seem like unlikely partners: the brain is squishy and is the command center of our bodies, while bones are hard and seem to just help us move and add stability. In reality, bones have cells that resemble and function like neurons, are full of nerves that exchange information with the brain and share a lot of signaling molecules with brain cells.
The first connection between bones and the brain is seen when we look at a bone cell called the osteocyte. Osteocytes, the most abundant bone cells in the skeleton, are interconnected through cellular branches called dendrites, allowing them to send and receive information from other cells. As shown in Figure 1, osteocytes have very similar dendritic networks to neuronal networks, but this similarity doesn’t end with their appearance. To prevent fracture formation, our bones sense the mechanical forces we put on them when we exercise so that high-strain areas can be reinforced with more bone. However, since bones are so stiff, the cells inside couldn’t detect these forces without the help of osteocytes. Osteocyte dendrites extend through fluid-filled channels within bones and when forces are applied, this fluid flows over the dendrites to generate shear stress that osteocytes can sense and interpret. They then send signals to bone cells called osteoblasts to reinforce areas experiencing more mechanical forces. Osteocytes also exchange information through their dendrites with other cells and parts of the nervous system, allowing them to influence parts of the body outside of bones (1). These similarities in form and function have led to many bone researchers referring to osteocytes as the “brain of the bone”.
Bone is also connected to the brain indirectly through the central nervous system (CNS) and directly through the peripheral nervous system (PNS). The CNS is made up of the brain and spinal cord and is responsible for receiving signals from nerves, interpreting them, and sending out signals to parts of the body to enact on the interpreted information. The PNS is composed of every other part of the nervous system, largely nerves, and sends sensory information to the brain while performing the brain’s commanded functions. The CNS and PNS work together to coordinate bodily functions from the automatic, like breathing, to the manual functions like walking (2). Bones are full of nerves in the PNS and these allow for bidirectional communication between the bone and brain during development, exercise, and injury healing (3–5).
In addition to having lots of nerves, bone also has bone marrow and blood vessels that allow for the exchange of signals between the bone and the brain through the bloodstream. In fact, bone cells can release signaling molecules that are able to cross the blood-brain barrier (BBB), influencing brain development and function. The BBB is a biological filter that controls what can pass between the bloodstream and the brain, in order to protect the brain from dangerous organisms or substances that may be in our blood. Due to its function, the BBB is impermeable to many signals that the body exchanges through the blood, but some bone signals have developed to cross the BBB to allow bones to influence the brain. Neurons have signaling molecules that, once released, can bind and influence bone cells, and both neurons and bone cells can release cellular packages, called extracellular vesicles, full of proteins or chemicals that can change cellular health and functions, some of which can even cross the BBB (1,6–9).
Bones and Neurodegenerative Diseases
Neurodegenerative diseases like Parkinson's Disease, Alzheimer’s Disease, Huntington’s Disease, and Amyotrophic Lateral Sclerosis (ALS) are all associated with changes in bone cell shape, health, or function and changes in bone mineral density (BMD) (1,7,9–13). In some cases, like in ALS, neurodegeneration of motor neurons decreases one’s ability to move and thus reduces mechanical forces sensed by bones, leading to decreased BMD and increased bone fracture risk (5,10,14). Additionally, a study done in a rat model of Parkinson’s Disease showed that the damage to neurons caused by the model led to a significant increase in osteocyte death, which is associated with osteoporosis, also often seen in patients with Parkinson’s Disease (11). The exact connection between the brain and bones that causes bone cell death with neuron damage is still being investigated, but this study demonstrates that damage to neurons besides motor neurons also causes changes in bone health. Overall, patients with neurodegenerative diseases often also display bone disease, including osteoporosis, increased fracture risk, and osteoarthritis, and the mechanisms behind these comorbidities are not fully known. Alternatively, some genetic skeletal disorders, like cleidocranial dysplasia and Coffin-Lowry syndrome, cause dramatic changes in the skeleton and bone cell behavior but often also display cognitive developmental delay or neurodegeneration. These negative cognitive effects are thought to be due to mutations in genes that encode substances that are needed by both brain and bone cells, reinforcing that bones can influence brain health too (13).
Treating the Brain through Bones
One of the major challenges in diagnosing neurodegenerative diseases today is the lack of specific tests (for example, imaging markers or secreted factors) that indicate specific diseases, as many neurodegenerative diseases can present similarly in functional impairment and brain appearance. Neurodegenerative diseases are also often diagnosed late due to their insidious onset, but if the connections between bones and the brain are further understood, bones could be used to assess neurodegenerative disease risk. Ample data support the idea that low BMD is correlated to an increased risk of neurodegenerative conditions, and BMD can be measured noninvasively using dual-energy X-ray absorptiometry (DEXA) scans, which are a common clinical practice (1,13). Identifying patients who have lower BMD can allow doctors to intervene with dietary changes, changes to physical exercise, and drugs that influence calcium metabolism or bone cell activity (3,5,9). Animal studies have also shown promising results in treating neurodegenerative conditions through bones. One study of Huntington’s Disease in mice showed that bone marrow transplantation could improve movement and neuron connections (12,15). This is believed to occur through the replacement of diseased immune cells in the bone marrow (which may damage the CNS through increased inflammation and immune cell activity) and an increase in BBB permeability (due to the total body irradiation that is required for bone marrow transplantation), which allows growth factors to enter the brain and increase connections between neurons.
By investigating the fascinating connection between bone and brain, scientists and clinicians could uncover methods of diagnosing and treating brain diseases that are less invasive and more accessible to patients. However, health doesn’t have to wait for the doctor’s office. A healthy brain and skeleton rely on a balanced diet and regular exercise. So, when you’re deciding on a 2025 New Year’s resolution, consider doing your brain a favor and taking care of your bones.
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