The effect of post‐extraction socket preservation laser treatment on bone density 4 months after extraction: Randomized controlled trial

Abstract Background Post‐extraction bone resorption may affect the outcome of ensuing restorations. Purpose This study aimed to evaluate a comprehensive laser post‐extraction protocol by comparing resulting alveolar bone regeneration with that obtained after standard extraction procedure. Materials and Methods About 53 simple extractions were randomized to either laser or control group. In the laser group, erbium (Er:YAG; 2940 nm) and neodymium (Nd:YAG; 1064 nm) lasers were used for degranulation, disinfection, de‐epithelialization of the surrounding gingiva, clot stabilization, and photobiomodulation. The primary outcome measure was change in bone density in the extraction area between day 1 and 4 months after extraction. Patients were monitored for potential side effects. Results Increase in bone density at the follow‐up CBCT was significantly higher in laser than in control group (p < 0.001). No post‐operative pain, bleeding, or swelling was present in the laser group. In the control group, one patient had bleeding 3–5 days after extraction, two patients had swelling and three patients reported post‐operative pain rated 3–5 on a 0–10 pain scale up to 3 days after extraction. Conclusions The proposed laser post‐extraction procedure is a safe and effective method to improve post‐extraction bone healing.


| INTRODUCTION
Alveolar bone and soft tissue remodeling is a normal physiological response following tooth extraction. 1 The resorption process varies amongst patients and tooth position and may be affected by several factors such as the presence of infection, previous periodontal disease, the extent of a traumatic injury, and the number or the thickness of the bony socket walls. 1 An equilibrium is reached approximately 3-4 months post-extraction. 1 The clinical consequences of postextraction remodeling may affect the outcome of the ensuing therapies aimed at restoring the lost dentition, either by limiting the bone availability for ideal implant placement or by compromising the aesthetic result of the prosthetic restorations. 2 Therefore, effective methods of reducing bone loss, accelerating bone healing, and making it more predictable are actively sought. Most studies focus on drugs or surgical techniques but more recently other modalities affecting the healing process have been investigated. 3 Among them is the use of laser therapy. 3 Photobiomodulation (PBM) is probably the best researched use of lasers in post extraction healing. 2,4 Recent reviews of accumulated animal and clinical studies reported that laser PBM therapy induced higher concentration of osteogenesis markers, as well as higher bone density and concluded that PBM improved the post-extraction healing process, however, the results vary with laser wavelength and parameters used. 2,4 PBM with Nd:YAG laser has been found to improve healing after extraction in patients at high risk for osteonecrosis. 5 Lasers also have other potential uses in the post-extraction procedure.
Use of Er:YAG laser for degranulation has been studied in periodontal and peri-implant treatment and seemed to promote reosseointegration on contaminated implant surfaces to a greater degree than alternative methods. 6 The advantages of laser degranulation are improved hemostasis and disinfection 6 and Er:YAG laser may be safely used because its high absorption in water results in very efficient ablation with minimal thermal effect. This property of the Er: YAG laser also allows for very fine control of depth of ablation, which makes it highly suitable for fast and safe de-epithelialization of the gingiva surrounding the extraction socket. 7 This de-epithelialization prevents ingrowth of epithelium into the socket and at the same time, produces an ablated rough surface, which may enhance retention of the blood clot. 6 Blood clot is very important for proper uncomplicated socket healing. 8 Laser irradiation of bleeding sockets may facilitate immediate clot formation and hemostasis. 6 Different types of lasers and diodes have been used successfully to coagulate blood and prevent the loss of blood clot from extraction sockets in animal studies, resulting in improved alveolar bone preservation. 6 In periodontal treatment, Nd: YAG laser has been demonstrated to be effective in fibrin clot stabilization in the periodontal pocket resulting in improved clinical outcomes. 6 Bactericidal effect of laser therapy is considered advantageous for postoperative wound healing because lasers are capable of creating a disinfected field during surgery and reducing the risk of infection. 6 In addition, because the Nd:YAG laser exhibits selective absorption in pigments, it is conceivable that this laser would be effective for devitalizing some of the pigmented bacteria, such as Porphyromonas gingivalis, that are associated with periodontal disease. 6 This aspect may be particularly relevant for extractions performed due to periodontal disease. Moreover, lasers can ablate or inactivate toxic substances, such as bacterial endotoxins (lipopolysaccharide) which may positively influence wound healing of the treated site and offer several advantages over conventional mechanical treatment. 6 Most clinical studies of the effect of laser therapy on postextraction healing have focused solely on photobiomodulation. 2,4 The aim of this study is to objectively evaluate a comprehensive postextraction laser protocol consisting of degranulation, disinfection, deepithelialization, clot stabilization, and photobiomodulation using Er: YAG and Nd:YAG wavelengths by comparing resulting alveolar bone regeneration (measured from CBCT) with that obtained after standard extraction procedure.

| Patients
Participants for this randomized clinical trial were recruited among patients attending our clinic between August and November 2019.
Inclusion criteria were patients of either sex, aged 18-80 years, in whom simple tooth extraction was indicated, who agreed to participate in the study and signed informed consent. Exclusion criteria were pregnancy, use of photosensitizing medication, medication that would compromise bone healing, and complicated extraction.
Extractions were randomized into laser and control groups (1:1) through drawing of closed envelops. The study was approved by the National Medical Ethics Committee (0120-409/2019/5) and conducted according to the principles outlined in the Declaration of Helsinki. The protocol was registered at ClinicalTrials.gov (NCT04232202).
Power analysis was based on the primary outcome measure; the change in bone density. We assumed a large expected effect size of 0.9 for this study. We calculated that 21 teeth per group would be needed to have 80% power to detect such a difference with a test at two-sided α = 0.05 (GPower 3.1 statistical software, Kiel University, Germany).
Additional patients were recruited to account for uncertainties in effect size estimation and loss during follow up.

| Procedure
Initial diagnosis was based on stomatological examination. Patient age, sex, number, location, and type of teeth extracted and indication What is known: • Recent systematic reviews suggested that laser photobiomodulation improves post-extraction healing.
• Bactericidal and hemostatic effects of lasers may make them useful tools also in post extraction socket cleaning and disinfection, de-epithelialization of the gingiva surrounding the extraction socket, and blood clot stabilization, but a comprehensive approach has not been studied.

What this study adds:
• This study is the first registered randomized controlled trial evaluating a comprehensive post-extraction laser protocol by comparing resulting alveolar bone regeneration (measured from CBCT) with that obtained after standard extraction procedure.
• The laser post-extraction procedure resulted in improved bone density and fewer side effects.
for extraction were recorded. Local anesthetic (Scandonest 2%, 1.7 ml) was administered before extraction in both groups.
In the control group the standard post-extraction procedure was carried out with cleaning of the post-extraction socket with an alveolar spoon.

| Statistical analysis
Linear mixed model (as implemented in the function lme from the package nlme 9 in R statistical software 10 ) was used to test the difference between laser and control group with change in bone density as the independent variable, intervention as the fixed factor and patient as the random factor, to account for non-independence of teeth from the same patient. The influence of the following covariates on the results was tested in sensitivity analyses: patient age, sex, indication for extraction (periodontitis/granuloma/other), extractions adjacent to the extracted tooth (no/yes), extraction site (maxilla/mandible), tooth location (anterior/posterior), time after extraction (days), and initial bone density (GSV).

| RESULTS
About 24 patients with 42 extracted teeth finished the study including the 4-month CBCT scan (Figure 3). Patient demographics are presented in Table 1. The laser procedure takes about 5 minutes longer than the standard extraction procedure. No post-operative pain, bleeding, or swelling was present in the laser group. In the control group, one patient had bleed-  Table 2 and show a significant effect of laser treatment even when all potentially relevant factors are controlled for. The only statistically significant covariate was GSV value at initial CBCT. Figure 6(B) shows that final bone density was higher in the laser group regardless of the initial bone density.
Coefficient estimates also indicate slower bone healing in patients 60 years old or older but the confidence interval is too wide to draw conclusions ( Table 2). The effect of patient age on change in bone density differed between groups (Figure 6(C)). Bone healing decreased with age in the control group but not in the laser group, indicating that older patients may benefit even more from laser treatment.
It was not possible to explore the effect of the indication for extraction on the outcome, because most patients in both groups had teeth extracted due to periodontal disease (Table 1, Figure 6   An advantage of this study is use of an objective outcome measure. Bone density was estimated from voxel values (GSV) of CBCT images.
There is some lingering controversy regarding the use of GSV for bone density evaluation since Hounsfield units (HU) are not directly applicable for CBCT. 21,22 Multiple studies have shown that when the same CBCT scanner is used, the grey value of scanned bone can be directly converted to the corresponding bone mineral density value using a linear calibration curve. 21 High correlation has been found between voxel value of CBCT and CT. 21 However, GSVs may shift owing to the use of different CBCT devices, exposure parameters, the position of the measurement in the field of view (centrally vs. peripherally), and the amount of mass inside and outside the field of view, introducing errors to quantitative estimates of actual bone density. 22 Nevertheless, there is agreement that GSVs can be used to evaluate bone density in a relative way 21,22 ; by pre-treatment and post-treatment comparison of CBCT GSVs when scanning patients under the same exposure conditions, especially if changes in bone density are relatively large. 22 Furthermore, bone quality evaluated by CBCT shows a high correlation with the primary stability of dental implants. 21 CBCT grey scale evaluation of bone density is preferred over CT despite somewhat lower accuracy due to reduced cost and radiation dose. 21

| CONCLUSION
A comprehensive laser post-extraction protocol using Er:YAG and Nd: YAG laser wavelengths for degranulation, disinfection, de-epithelialization, clot stabilization, and photobiomodulation of the extraction socket proved to be effective in increasing bone density 4 months after extraction in comparison with controls, resulting also in fewer side effects. Our data suggests that addition of lasers to postextraction protocol may be especially beneficial for older patients and patients with chronic periodontitis. Reduced rate of complications and improved bone healing allow earlier restoration, support better aesthetic outcomes after prosthetic restorations and facilitate optimal placement of implants.