Schizophrenia is usually described as a disorder of thought, perception, and behaviour — a disease of the brain. Yet for years, researchers have noticed a quieter, more persistent pattern in the lives of people with the condition. Compared to the general population, they are more likely to have weaker bones and to suffer fractures, in part because of disruptions in metabolic processes involved in bone health.
The reasons are familiar: long-term use of antipsychotic drugs can affect the body’s metabolism and hormone balance. People with schizophrenia are also more likely to be physically inactive or to smoke, and vitamin D deficiency is common. Each of these factors increases fracture risk. Together, they help explain why bone problems are more frequent, but they don’t fully explain how schizophrenia and fragile bones might be biologically connected.
It is this unanswered question that a genetic study published in Genomic Psychiatry set out to explore: whether part of the link between schizophrenia and bone health might be rooted deeper than behaviour, treatment or circumstance.
A new attempt
To understand whether the connection has a deeper biological basis, a team led by geneticist and associate professor Feng Liu at Tianjin Medical University General Hospital, China, turned to DNA.
Using data from more than half a million individuals drawn from international genetic studies of schizophrenia and osteoporosis, the researchers conducted an analysis large enough to unearth, if they were present, shared genetic patterns in much more detail than earlier work. The goal was not to find a single bone gene or to suggest that schizophrenia causes osteoporosis but to check whether the two conditions shared any genetic influences at all.
Previous genetic studies had found only weak links between schizophrenia and measures of bone strength, but Liu’s team argued that that wouldn’t mean the two conditions are unrelated. Many genetic analyses look for broad patterns across all of a person’s DNA at once. When some DNA changes increase risk while others decrease it, those effects can cancel each other out, making the connection disappear. And if shared genetic effects exist only in a few small stretches of DNA, they would be easy to miss.
To get around this, the researchers used newer tools that looked for shared DNA regions one by one, rather than averaging everything together. This allowed them to detect overlap even when genetic effects were uneven or pointed in different directions. Of course this process is also more laborious.
Note: in genetic research, the word ‘shared’ can be misleading. Prof. Liu explained that the study identified regions of DNA that are associated with both schizophrenia and bone-related traits. But this doesn’t mean the same gene directly causes both conditions. Instead it suggests that certain stretches of DNA may influence brain function and bone health through different processes in the body.
Not all bones
The shared genetic signals were not spread evenly throughout the skeleton. Among the bone measurements the team analysed, heel bone strength stood out, accounting for most of the DNA regions shared with schizophrenia. The overlap was much weaker for other parts of the body. In the forearm, for instance, the researchers found no clear shared genetic signal at all.
Part of this uneven pattern may come down to numbers. Heel bone density has been measured in far more studies than many other skeletal sites, making it easier to detect small genetic effects. Biology may also play a role. The heel bears weight and is shaped by whole-body processes such as metabolism and development, which could overlap with pathways involved in schizophrenia. Prof. Liu cautioned that separating these explanations will require more research that measures different bones in similarly large populations.
For now, taken together, the results suggest shared genetic influences, where they exist, are highly specific to certain parts of the skeleton.
Effects on care
For clinicians, the findings do little to alter what good care should already include. “We have known for decades that persons with schizophrenia die prematurely largely because of a higher burden of non-communicable diseases that are not recognised or poorly treated,” Vikram Patel, a psychiatrist and professor at Harvard Medical School, said.
The genetic patterns described in the study, Prof. Patel noted, “shed light on another possible mechanism through which these health conditions co-exist,” but have “little additional impact on the clinical care of persons with schizophrenia.”
Gap in psychiatric care
In everyday psychiatric practice, bone health is rarely front of mind. “Fracture risk and bone health are unfortunately not very visible in the care of patients with schizophrenia,” Akanksha Dadlani, a psychiatry fellow at Stanford University, said.
Clinicians are alert to immediate risks, she explained, such as sedation or falls when prescribing antipsychotic medications. But this attention is usually short-term, focused on sudden drops in blood pressure or balance rather than on bone loss or fracture risk years later.
“There is no standard practice within psychiatry for monitoring bone density or fracture risk in this population,” Dr. Dadlani said. “As a result, bone health tends to fall between specialties, creating a gap in care rather than an area of proactive management.”
Timing also plays a role: schizophrenia is often diagnosed in early adulthood, a stage of life when bone fragility is rarely a clinical concern. By the time fracture risk becomes more relevant later in life, long-term bone health may no longer be on clinicians’ radar.
By identifying shared genetic patterns between schizophrenia and bone-related traits, the study adds to growing evidence that schizophrenia involves biological processes affecting the body as a whole, not just the brain. While the findings don’t point to immediate clinical interventions, they reinforce the importance of considering physical health risks, such as bone fragility, as part of long-term and holistic psychiatric care.
Anirban Mukhopadhyay is a geneticist by training and science communicator from New Delhi.
