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Effect of orthodontic treatment on systemic inflammatory biomarkers in patients with malocclusion: A Systematic Review of Randomized Controlled Trials

This systematic review of three randomized controlled trials concludes that orthodontic treatment induces a transient, self-limiting local inflammatory response in gingival crevicular fluid without a dose-dependent relationship to force magnitude, but it fails to determine effects on systemic inflammation due to the absence of studies measuring circulating biomarkers.

Original authors: Fahad Aziz Khattak, Sana Ali Khan, Muhammad Usman Afridi, Aaeyla Wasif, Mahad Azhar

Published 2026-10-16
📖 5 min read🧠 Deep dive

Original authors: Fahad Aziz Khattak, Sana Ali Khan, Muhammad Usman Afridi, Aaeyla Wasif, Mahad Azhar

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

When a dentist moves a crooked tooth into a straighter position, they are not just applying mechanical pressure; they are triggering a biological conversation within the body. The space between a tooth and the gum, known as the periodontal ligament, acts as a shock absorber, but when force is applied, the cells in this tissue sense the stress and release chemical signals. These signals, often called inflammatory mediators, tell the body to break down bone on one side of the tooth and build it up on the other, allowing the tooth to slide into its new home. This process is well understood to happen locally, right where the tooth sits. However, a lingering question has puzzled researchers: does this local chemical storm ever become loud enough to be heard by the rest of the body? In other words, does the act of straightening teeth cause a measurable, body-wide inflammation that could affect a patient's overall health?

To answer this, a team of researchers from the Rehman College of Dentistry conducted a rigorous review of the best available scientific evidence. They searched for randomized controlled trials, which are the gold standard of medical research because they compare groups of people under strict conditions to isolate the effects of a treatment. Their goal was to find studies that measured specific immune markers in patients undergoing orthodontic treatment. They wanted to see if these markers, which act as flags for inflammation, rose significantly in the bloodstream or if the changes remained confined to the mouth. After sifting through hundreds of records and applying strict criteria, they found only three high-quality trials that met their standards. These studies involved 70 participants, ranging from children to young adults, and examined how the body reacted to the forces used to move teeth.

The results of this review revealed a clear boundary between the mouth and the rest of the body. None of the three studies measured the blood, plasma, or saliva for signs of systemic inflammation. Instead, every single study collected fluid directly from the tiny gap between the tooth and the gum, known as gingival crevicular fluid. This fluid is a local exudate, meaning it reflects what is happening immediately around that specific tooth, much like a puddle reflects the rain falling on a single roof rather than the weather across the whole city. Because no study looked at the circulating blood, the researchers could not determine if orthodontic treatment causes a body-wide inflammatory response. The question of whether straightening teeth affects overall systemic health remains unanswered by the current randomized evidence.

What the studies did find was a distinct, temporary reaction right at the site of the tooth movement. When an acute stimulus was applied, such as placing a rubber separator between teeth to create space, the local concentration of a protein called interleukin-1 beta rose sharply. This spike happened quickly, reaching its highest point just one day after the force was applied, and then it settled back to normal levels within a week. Another marker, tumor necrosis factor-alpha, showed a different pattern depending on the type of treatment. In one study involving a surgical extraction followed by a special healing plug, this marker rose significantly one and two weeks after the procedure before returning to baseline. In another study using a continuous force to push a tooth backward, the rise in this same marker did not appear until 28 days later. These findings suggest that the timing of the chemical response depends heavily on the nature of the force and the type of injury or movement, creating a local, self-limiting inflammation that resolves on its own.

The researchers also investigated whether using stronger forces would speed up the process or create a more intense reaction. They compared a lighter force of 75 grams against a heavier force of 150 grams. Contrary to what one might expect, the heavier force did not produce a greater surge in inflammatory markers, nor did it move the teeth any faster. In fact, the teeth moved at nearly the same rate regardless of the force applied. In some cases, the higher force actually resulted in lower levels of certain chemical signals at the pressure site after 24 hours. This indicates that simply pushing harder does not necessarily make the biological machinery work faster or louder, and it certainly does not guarantee a more efficient outcome.

Ultimately, this review highlights a significant gap in our knowledge. While we know that moving teeth causes a temporary, localized inflammation in the gums that peaks within days and fades within weeks, we do not yet know if this local activity ever translates to a systemic effect. The available evidence is limited because no high-quality trial has yet measured the inflammatory markers in the blood of patients undergoing orthodontic treatment. Until such studies are conducted, the idea that orthodontic therapy triggers a body-wide inflammatory response remains an open question, not a proven fact. The current data confirms that the mouth reacts to the work being done, but it does not tell us if the rest of the body notices.

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