For most of our lives, bones seem to have one straightforward job: hold the body together. They support our weight, protect delicate organs, provide leverage for muscles and store minerals such as calcium and phosphorus. Their importance becomes obvious after a fracture, but their everyday activity is easy to overlook.
Inside the skeleton, however, an intricate biological system is constantly at work. Bone tissue is broken down and rebuilt, specialised cells sense mechanical forces, and chemical signals move between the skeleton and other parts of the body. Some of those signals can travel through the bloodstream, influencing organs far removed from the bones that produced them.
This has changed how researchers think about the skeleton. Bone is not simply a rigid framework that responds to instructions from the rest of the body. It can also act as an endocrine organ—a tissue that releases chemical messengers capable of influencing distant cells and organs.
One of the best-studied examples is osteocalcin, a protein produced by bone-forming cells. Research has linked it to glucose regulation, insulin production and brain function, although important questions remain about how consistently these effects operate in humans. Other bone-derived signals help regulate mineral balance, while communication between bone, bone marrow and immune cells connects the skeleton to the body’s defence system.
The emerging picture is more complex than the familiar idea that bones merely hold us upright. The skeleton is part of a wider communication network involving metabolism, the nervous system and immunity.
Understanding that network could eventually improve how scientists investigate conditions such as osteoporosis and metabolic disease. It does not mean that bone hormones are ready-made treatments, or that every discovery in laboratory animals applies directly to people. But it does suggest that healthy bones matter for reasons extending well beyond strength and mobility.
What does it mean for bones to be endocrine organs?
Bones have traditionally been discussed in a different context: structure, movement and mineral storage. Yet researchers have identified several molecules produced or regulated by skeletal tissue that also participate in communication with other organs.
A major development in this field was the discovery that osteocalcin, a protein made by osteoblasts, may function as a hormone. Osteoblasts build new bone by producing the matrix that later becomes mineralised. As the skeleton remodels itself, some of the molecules associated with this activity enter circulation and can influence tissues elsewhere.
A review published in Endocrine Practice, available through the National Library of Medicine’s PubMed Central archive, describes how research into osteocalcin helped establish the idea that bone can regulate physiological processes beyond mineral metabolism.
The skeleton also produces other signalling molecules. Osteocytes—cells embedded within the bone matrix—help sense mechanical forces and regulate remodelling. They produce sclerostin, which influences bone formation, and fibroblast growth factor 23, or FGF23, which helps control phosphate balance and vitamin D metabolism.
These molecules do not all operate in the same way. Some act locally within bone tissue; others affect distant organs. Calling bone an endocrine organ is therefore not a claim that every bone-derived substance is a circulating hormone. It reflects the broader finding that skeletal tissue participates in chemical communication throughout the body.
This is an active area of research, and the evidence differs depending on the molecule and the biological effect being studied. Some functions are well established in human physiology, while others remain supported mainly by animal experiments.
Osteocalcin: the bone protein attracting the most attention
Osteocalcin has become a central focus of research into bone’s endocrine functions. It is produced by osteoblasts and is abundant in the bone matrix, where it is associated with the process of mineralisation.
For years, scientists largely studied osteocalcin in the context of bone formation. Research later suggested that certain forms of the protein can also act beyond the skeleton, influencing metabolism and other physiological processes.
The details matter. Osteocalcin undergoes a chemical modification called carboxylation, which affects its interaction with the mineral component of bone. Researchers have investigated whether the undercarboxylated form is particularly important for some of its proposed hormonal effects.
Much of the foundational evidence came from experiments in mice. Those studies suggested that osteocalcin could affect insulin secretion, insulin sensitivity and energy use. Researchers have also investigated possible effects on the brain and reproductive system.
A detailed review in the journal Current Osteoporosis Reports summarises this research and the biological mechanisms proposed for osteocalcin. It is available through PubMed.
But a key distinction remains: evidence that a molecule has a hormonal function in mice does not automatically establish that it has the same effect, to the same degree, in humans.
Human studies have found associations between circulating osteocalcin and measures of glucose metabolism. However, those findings do not by themselves prove that osteocalcin directly causes improvements in blood sugar regulation. Age, physical activity, kidney function, vitamin K status and the rate of bone turnover can complicate the relationship.
A review in Nature Reviews Endocrinology examines these uncertainties, including the difficulty of distinguishing osteocalcin’s role as a marker of bone formation from its possible role as a metabolic regulator. Read the review, “The role of osteocalcin in human glucose metabolism: marker or mediator?”.
The research is promising, but it has not turned osteocalcin into an established treatment for diabetes or other metabolic conditions.
How the skeleton communicates with the pancreas
The pancreas is central to controlling blood glucose. Specialised beta cells within the pancreatic islets release insulin when blood glucose rises. Insulin helps tissues take up and use glucose, keeping the body’s energy supply within a healthy range.
Animal research suggests that bone-derived osteocalcin may participate in this process.
In experiments involving mice, researchers have reported that osteocalcin signalling can influence beta-cell activity and insulin production. Studies have also suggested that it may affect how sensitive certain tissues are to insulin. These findings have led scientists to investigate a possible feedback loop between the skeleton and the body’s energy-regulating systems.
The idea is biologically intriguing. Bone is metabolically active tissue, and maintaining, repairing and rebuilding the skeleton requires energy. A chemical signal connecting bone activity with glucose regulation could help coordinate these processes.
The relationship may run in both directions. Insulin signalling can influence bone cells, while skeletal hormones may affect metabolic pathways. Rather than functioning as separate systems, bone and the pancreas may participate in a network in which signals from one tissue influence the behaviour of another.
However, the human evidence remains less conclusive than some popular descriptions suggest. Researchers have reported relationships between osteocalcin levels and markers of glucose metabolism, but clinical studies have not established a simple rule that more osteocalcin necessarily means better blood sugar control.
It would therefore be premature to describe osteocalcin as a proven natural way to prevent diabetes. Nor is there sufficient evidence to recommend supplements intended to manipulate osteocalcin for that purpose.
The scientific question is more specific: under what conditions does bone-derived signalling meaningfully influence human glucose regulation, and could those pathways eventually be targeted safely?
That distinction separates a promising research direction from a medical recommendation.
The bone–brain connection: can the skeleton influence cognition?
The brain and skeleton already communicate through well-established pathways. The nervous system helps regulate bone remodelling, and hormones affecting the body can influence both tissues. Researchers are now investigating whether bone-derived molecules also act directly or indirectly on brain function.
Osteocalcin is a leading candidate. Experiments in animals have linked it to processes involving neurotransmitters, learning, memory and behaviour. These findings have encouraged researchers to investigate whether skeletal signals contribute to brain development and the maintenance of cognitive function.
A review published in Molecular Brain explores the proposed relationship between osteocalcin and the central nervous system, including possible implications for cognition and motor-related disorders. The paper is available here.
The potential significance is substantial, but it is also an area where caution is essential.
Animal experiments allow scientists to manipulate specific genes and signalling pathways, then observe changes in brain function. Such studies can reveal mechanisms that would be difficult to investigate directly in humans. Yet human cognition is shaped by many interacting factors, including age, sleep, cardiovascular health, education, medication and neurological conditions.
Evidence that osteocalcin influences memory-related processes in an animal model does not mean that a person’s bone health can be used to predict intelligence, or that increasing the hormone would prevent dementia.
Scientists still need to establish which forms of osteocalcin reach relevant brain regions, how they interact with receptors, and how important those effects are in humans under ordinary physiological conditions.
The brain–bone relationship also works in the other direction. Physical activity is controlled by the nervous system, while the mechanical forces created by movement help maintain bone. Neurological conditions that reduce mobility can contribute to bone loss, illustrating how changes in one system may affect another without requiring a single hormone to explain the whole relationship.
The emerging research is therefore not a claim that bones control the brain. It is evidence that the skeleton may be one participant in a larger network of signals that help coordinate bodily function.
Why bones and the immune system are closely connected
The skeleton’s relationship with immunity is more firmly grounded in anatomy and cell biology.
Much of the body’s blood-cell production takes place in bone marrow, the soft tissue inside many bones. Marrow contains haematopoietic stem cells, which can develop into red blood cells, platelets and the white blood cells needed for immune defence.
The marrow is not simply a container for these cells. Its environment helps regulate their survival, development and movement. Bone-forming cells, osteocytes, blood vessels, stromal cells and immune cells interact through chemical signals and direct contact.
This relationship is often described as osteoimmunology—the study of interactions between the skeletal and immune systems.
One important example involves RANKL, a signalling protein that helps regulate the formation and activity of osteoclasts, the cells that break down bone. RANKL also has important roles in immune-cell biology. Its activity is controlled by a network of other molecules, including osteoprotegerin, which can bind RANKL and limit its interaction with its receptor.
These pathways matter because bone formation and bone breakdown must remain balanced. If bone resorption outpaces formation over time, skeletal strength can decline. Immune signalling can influence this balance, particularly during inflammation.
A review in the journal Calcified Tissue International and related research on osteoimmunology describe how immune mediators and bone-remodelling pathways intersect. A broader overview of communication between bone and other organs is available in this open-access review on bone crosstalk.
The connection becomes especially visible in inflammatory diseases. In rheumatoid arthritis, for example, persistent inflammation can contribute to local bone erosion around affected joints. In other circumstances, immune signals can influence bone turnover throughout the body.
This does not mean that every immune response damages the skeleton. Inflammation is a normal part of defence and repair. The outcome depends on the signals involved, their duration and the surrounding biological conditions.
Researchers are studying these interactions to better understand bone loss associated with chronic inflammatory disease and to identify ways of protecting skeletal tissue without undermining essential immune functions.
Bone also communicates with the kidneys and helps regulate minerals
Another important part of the story is FGF23, a hormone produced mainly by osteocytes and osteoblast-lineage cells.
FGF23 helps the kidneys regulate phosphate, a mineral essential for bones, teeth, cell membranes and energy metabolism. It also influences the production of active vitamin D, which helps the body absorb calcium and phosphate.
The relationship illustrates a clear endocrine function of the skeleton. Bone tissue senses and responds to changes in the body’s mineral environment, while FGF23 travels through the circulation and acts on the kidneys. The kidneys, in turn, influence the mineral supply available to the skeleton.
This is a carefully regulated system. Too little or too much phosphate can cause significant health problems, and abnormal FGF23 activity is associated with several disorders involving phosphate balance and bone mineralisation.
Unlike some proposed effects of osteocalcin on cognition or glucose metabolism, the role of FGF23 in phosphate regulation is an established part of human physiology. The National Institute of Diabetes and Digestive and Kidney Diseases provides background on mineral and bone disorders associated with kidney disease.
This example also explains why scientists need to be precise when describing the skeleton as an endocrine organ. Some bone-derived hormones have well-defined clinical importance, while other proposed functions remain under investigation. They belong to the same broad field, but the strength of the evidence is not identical.
What does this mean for osteoporosis and metabolic disease?
Osteoporosis is characterised by reduced bone strength and an increased risk of fractures. It is influenced by age, hormonal changes, genetics, nutrition, physical activity, medication and other health conditions.
The discovery that bone participates in wider metabolic signalling has encouraged researchers to ask whether changes in skeletal biology might be connected to conditions beyond the skeleton itself.
For example, scientists are investigating relationships between bone turnover and metabolic health, including obesity and type 2 diabetes. They are also studying whether specific signalling pathways could eventually provide new therapeutic targets.
There are important reasons to pursue this research. A treatment that safely modifies a relevant pathway could potentially offer benefits beyond bone density. But developing such a treatment requires a detailed understanding of how the pathway works in humans and whether changing it has unwanted effects elsewhere.
Bone is not an isolated target. Osteocalcin-related pathways, for example, may interact with several tissues. A drug that alters one signalling process could have consequences for metabolism, reproduction or other physiological functions. Researchers need to identify the appropriate target, dose and patient population before a laboratory finding can become a clinical therapy.
For now, established approaches to protecting bone health remain important: adequate nutrition, appropriate weight-bearing and resistance exercise, avoiding smoking, limiting excessive alcohol consumption and seeking medical assessment when fracture risk is elevated. People with osteoporosis or other medical conditions should follow advice tailored to their circumstances.
The endocrine discoveries do not replace these measures. They add another layer to the scientific understanding of why skeletal health matters.
What scientists still need to discover
The idea that bones communicate with other organs is no longer merely speculative. Hormones such as FGF23 have established roles in human physiology, and osteocalcin research has produced substantial evidence for endocrine functions, especially in animal models.
The unresolved questions concern the details: how large these effects are in humans, which molecular forms are active, how they vary with age and health, and whether the pathways can be targeted safely.
Researchers also need better ways to separate cause from correlation. If people with certain osteocalcin levels tend to have different metabolic outcomes, that relationship may reflect a direct hormonal effect, changes in bone turnover, another underlying condition or several factors at once.
Large, carefully designed human studies are needed to untangle those possibilities. Laboratory research remains important, but clinical evidence is essential before proposed bone-hormone therapies can be recommended.
The field is also expanding beyond osteocalcin. Scientists are examining how sclerostin, RANKL and other bone-derived signals participate in communication between skeletal tissue and other organs. The challenge is to understand how these molecules interact as a system rather than treating each one as an independent switch.
The skeleton is more than a framework
The familiar image of bone as a rigid support structure is incomplete. Living bone is constantly rebuilt, responds to mechanical forces, helps regulate mineral balance and provides a specialised environment for blood-cell development. It also releases signals that can influence tissues elsewhere in the body.
Some of the most exciting questions concern the potential links between bone, the brain and metabolism. Other connections, including the roles of FGF23 in mineral regulation and bone marrow in blood-cell production, are already central to human biology.
The next stage of research will determine how much these networks can tell us about disease—and whether they can lead to better treatments. For now, the evidence supports a compelling conclusion: the skeleton is not merely something the body carries around. It is an active part of the body’s communication system.
