We read with interest the article by Professor Flórez-Moreno et al in the January issue investigating salivary levels of sRANKL and OPG and their ratios during orthodontic tooth movement, in an effort to determine the possibility of using these as biomarkers for chair-side point-of-care testing. The authors based their methodology on the premise that, as the different mediators involved in alveolar bone remodeling are being continuously washed into saliva by gingival crevicular fluid, unstimulated whole saliva could be an easier alternative to gingival crevicular fluid sampling of isolated sites. Although it is not our intention to detract credit from the findings of their study, we would prefer to interpret their findings with caution in light of the following.

First, current ELISA techniques used to quantify RANKL and OPG levels even in serum are not very sensitive. Since sensitivity of assays is a critical factor in studies of this nature, one can arguably be more accurate when gingival crevicular fluid exudate is used for testing rather than whole saliva. Furthermore, gingival crevicular fluid provides a more accurate noninvasive site-specific method of assessing local tissue reactions to orthodontic force. Second, RANKL and OPG are locally active molecules, and even gingival crevicular fluid tested from sites close to the area of the experiment might only partially reflect the actual local mechanism. Finally, no reference ranges have been established regarding RANKL and OPG serum levels. They tend to vary from one study to another, depending on the assays used. Currently, standard levels for RANKL and OPG are not well established.

Nevertheless, it is essential to develop such point-of-care testing devices because we know that each patient responds differently to applied orthodontic forces. The authors have rightly pointed out that the analytes tested “might serve in a panel of salivary functional biomarkers” for effective screening in clinical practice. Other plausible analytes that could be further studied are matrix metalloproteinases (specifically, MMP-8, MMP-13, and others). A recent study along similar lines investigating the diagnostic potential of matrix metalloproteinases and their bioactive regulators in gingival crevicular fluid as biomarkers of orthodontic tooth movement showed great potential as a chair-side point-of-care test. We hope that, in the not too distant future, such testing will become a reality, thereby giving us a clinical edge for enhancing diagnosis and aiding treatment planning for our patients.