Turns out, having those two different chromosomes has its pros and cons as a dental patient: cons when it comes to periodontal disease, some pros when it comes to perio treatment.
While the dental community has known for a while that periodontal disease is more frequent and severe among males,1 the reason for this has not been known until now.
A research team led by Julie Marchesan, DDS, Thiago Morelli, DDS, and Jenny PY Ting, PhD, published a study in the Proceedings of the National Academy of Sciences (PNAS) that uncovers a sex-dependent biological driver for periodontitis.
They found that a key component of the immune system, inflammasome, is the causal mechanism for the disease’s male bias, and confirmed that a targeted anti-inflammatory therapy is effective only in males.
How the studies were conducted
The research team from UNC-Chapel Hill analyzed more than 6,200 human samples in three different studies and used advanced mouse models. They found higher inflammation in males due to them having significantly higher levels of the inflammatory cytokine interleukin-1 beta. They also found that inflammasome drives bone loss only in males.
With these new biological findings, the researchers tested caspase-1/4 inhibitor (VX-765), a common anti-inflammatory drug that blocks the inflammasome's activation. They found that the inhibitor prevented bone resorption and reduced inflammatory signaling in male mice with experimental periodontitis but showed no protective effects in females.
The drug’s therapeutic effects depend on the male reproductive system being intact. When the testicles of male mice were removed, the inhibitor no longer worked.
What this may lead to
“Our findings not only pinpoint the inflammasome as the causal driver of male-biased periodontitis but also demonstrate a clear path for sex-stratified therapeutics in dentistry,” Dr. Marchesan told PANS. “The conventional one-size-fits-all approach to treating periodontitis must be re-evaluated. Future clinical trials and treatment strategies for periodontitis need to take biological sex into account to ensure therapies are effective for all patients.”
The researchers feel this study will lead to more targeted treatment for males, as well as help guide researchers to look for causes and treatments of bone loss in females.
Read the complete study here.
Reference
- Alves T, Swanson KV, Girnary MS, Marchesan JT. Inflammasome targeting for preiodontitis prevention is sex dependent. PANS. October 27, 2025. https://www.pnas.org/doi/10.1073/pnas.2507092122
