|Laser and Periodontal Diseases|
Low Level Laser Therapy
In The Treatment of Periodontal Disease
1. STUDY PURPOSE AND RATIONAL
The general objective of this study is to demonstrate that the application of low level laser therapy (LLLT) in addition to standard procedures employed to treat periodontal disease improves the outcome of the treatment.
Periodontal disease is an infectious process that is the leading cause of tooth loss in adults. It attacks the structures of the periodontium (the ligaments around the teeth), the gingivae, epithelial attachment, cementum that cover the root of the tooth, and the alveolar bone that supports the tooth. Periodontal disease causes a breakdown of the periodontium, resulting in loss of tissue attachment and destruction of the alveolar bone.
Almost 75% of the American adults have some form of periodontal disease, and most are unaware of the condition. Certain systemic conditions increase the patient’s susceptibility to periodontal disease, and periodontal disease, in turn, may increase a patient’s susceptibility to certain systemic conditions. Disease-causing bacteria are necessary for the periodontal disease to begin, but they are not solely responsible for the destruction of the periodontium. Other risk factors can also alter the body’s response to the bacteria present in the mouth. These factors include traumatic occlusion, overhanging restorations, sub-gingival placement of crown, orthodontic appliances or partial dentures may also contribute to the progression of the periodontal disease as well as smoking. Furthermore, the course of the disease is often influenced by other general medical factors, such as genetic preposition, specific medication, hormonal deregulation, and systemic disease, some renal or hepatic conditions, diabetes, osteoporosis, metabolic calcium dysfunction, immune system deficiency and stress.
Diabetes mellitus is a strong risk factor for periodontal disease. Diabetic individuals are three times more likely to have attachment and bone loss than non-diabetic patients. Furthermore, osteoporosis is always associated with alveolar bone loss. Women with osteoporosis have increased alveolar bone retraction, attachment loss, and tooth loss compared with women without osteoporosis. Estrogen deficiency has been linked to decreases in alveolar bone.
Tetracycline and non-steroidal anti-inflammatory drugs (NSAIds), have a
beneficial effect on the periodontium. At the same time they have a very toxic effect on the liver, which toxicity has a boomerang effect on the periodontium. Decreased salivary fluid (xerostomia) can be caused by more than 400 medications, including diuretics, antihistamines, anti-psychotics, anti-hypertension agents, and analgesics. Anti-seizure drugs and hormones such as estrogen and progesterone can cause gingival enlargement. Any of the above medications can accumulate to levels of hepatic and renal toxicity that will adversely affect periodontal tissue.
Since the seventies, not long after the construction of the first lasers, there was evidence that the laser irradiation can result in modulation (stimulation or inhibition) of biological processes. At the beginning, the Low Level Laser Therapy (LLLT) was empiric; it was not based on in vitro studies, so that the interaction mechanisms between the laser beam and the living mater were unknown. This empiric character of the clinical investigations lasted a long time, especially because the most medical laser users did not fully understood the principles of lasers, the characteristics of the laser beam, and the interaction mechanisms
Low level laser therapy (LLLT) is defined as application of laser light with an intensity of less than 250 mW/cm2 to treat various medical condition. Over the last 20 years, this therapy has been successfully applied to wound healing, pain management, for diabetes, in physiotherapy, dermatology, gynecology and dentistry. There is evidence that LLLT has an anti-bacterial effect, act as anti-inflammatory agent, and stimulates collagen and bone growth. Over the last decade, much progress has been made in elucidating the underlying principles.
Light is scattering the tissue in 3 manner possible: 1. Volumes of partially polarized light are formed, 2. Points of high light intensity appear, 3. Areas of high difference in light intensity levels are formed
When volumes of partially polarized light are formed, light is absorbed in cytochrome molecules and stimulates the creation of oxygen that leads to the formation of ATP, and stimulates cAMP and enzymes. Triggered immunological chain reaction occurs. Macrophages are activated. The number of mast cells increased as well as procollagen synthesis in fibroblasts, process that lead to anti-inflammatory actions, regeneration of the tissues and healing.
When points of high light intensity appear and also areas of high difference in light intensity levels are present, the electrical field across the cell membrane creates a dipole moment on the bar shaped lipids that influence the permeability of cell membrane that effects transport channels for Ca, Na, K. The receptor activity on cell membranes increase as well as the serotonin level in blood. In the same time LLLT stimulates synthesis of endorphins, decrease C-fiber activity and in the areas of high intensity levels, is increased nerve cell action potential. All this mechanisms influence the pain and anti-inflammatory process.
The FDA gave clearance for LLLT for following medical applications:
1. Temporary relief of minor muscle and joint pain.
2. The temporary relief of stiffness
3. The temporary relief of minor joint pain associated with arthritis
4. The temporary increase of local circulation where applied
5. The relaxation of muscles.
In this study we seek to study the effects of LLLT on advance chronic periodontities that have caused severe destruction of the periodontal structures, i.e. clinical attachment loss over 5 mm. increased bone loss, increased pocket depth (usually 5 mm or grater) and increased tooth mobility. The symptoms of the disease are a red, swollen, tender gingiva, bleeding while brushing, flossing or spontaneous, loose or separating teeth, pain or pressure when chewing, pus around the teeth or gingival tissues,
The promising results of prior clinical pilot studies involving human subjects with periodontal disease have provided the impetus for the proposed work. These studies showed that subjects receiving LLLT in addition to traditional treatment enjoyed markedly better recovery and healing than subjects treated without LLLT. LLLT resulted in shorter bleeding and pain recovery time, reduced post surgery complications (edema, inflammation, infection,), faster forming and maintaining of the clot, and better maintenance of the masticator functions. Overall we observed improved healing of the soft tissue, rapid recovery of a more compact bone tissue and stability restoring of the teeth, complete and maintenance of the masticatory and esthetic functions, with healthier gingival tissue. The effectiveness of LLLT varied somewhat as a function of the age, general health and metabolic problems of the patient. Very good results were obtained in diabetics for whom wound healing is compromised.
2. STUDY DESIGN AND STATISTICAL ANALYSIS
We plan to recruit approximately 200 patients (diagnosed with either diabetes or osteoporosis) evidencing marginally advanced chronic periodontitis. A correct diagnostic will be assessed based upon the medical and dental history. All of these patients will receive classic modern treatment. Approximately half of the diabetic patients and half of the patients with osteoporosis will receive LLLT in addition to the classical treatment. (The number of patients to be enrolled was determined by power calculations using the data obtained in our pilot studies assuming a significance level of =0.05 and power of =0.9)
For all four groups ((1) diabetic with LLLT, (2) diabetic without LLLT, (3) osteoporosis with LLLT, and (4) osteoporosis without LLLT) we will determine the mean and standard deviations of the following parameters
§ 1. gingival bleeding time
§ 2. pain relief time
§ 3. bone recovery time
§ 4. inflammation
§ 5. complete healing
§ 6. recurrence
These parameters will be quantified as follows:
1. Bleeding time. We considered the gingival bleeding time as the time interval from the end of the curettage until the formation of the blood clot, established by the paper test. The time will be measured with a chronometer. The measurement will be performed in one location.
2. Pain relief time. Pain is a physiological consequence of the surgical trauma, accompanied by inflammation. We asked the patients to note the evolution of the pain intensity, and if they could use the maxillaries for normal mastication. The time interval described by the patient until the complete resolution of pain will be measured.
3. Bone recovery time. We determine the bone regeneration by observing the plague healing evolution (disappearing of the dental mobility, improving of the gingival color, recuperation of the masticator function and the comfortable state of the patient) and by evaluating X-ray images. When clinical parameters indicate bone recovery, we will perform the radiography. We consider bone regeneration time to be the interval between the onset of treatment and the radiographic confirmation of bone regeneration.
4. Inflammation and edema, produced by bacterial over-infection or caused by other agents, are considered as a post surgery complication. We will measure the protein C reactive by laboratory serum analysis.
5. Long term healing is quantified by:
- rapidity of healing and the aesthetic aspect of the scar;
- stability restored of the teeth determined by tooth mobility measurements;
- documenting restored mastication and physiognomic functions.
6. The recurrence rate will be monitored and statistically quantified.
For all these parameters we will perform an analysis of variances (ANOVA) and the Bonferroni t-test to determine the statistical significance of the mean values for various cohorts. A statistical significance in the difference between patients treated with LLLT and not treated with LLLT will have been achieved and the clinical usefulness of LLLT established if the corresponding p-values are smaller than 0.05.
3. STUDY PROCEDURE
For each subject participating in this study a complete detailed diagnostic will be made based on the dental and medical history. A periodontal examination will include the assessment of:
1. Plaque – the primary cause of the inflammation;
2. Calculus – hard, mineralized plaque adherent on the surface of the teeth;
3. Gingival recession level - visualized on the chart by a dotted or colored line indicating the gingival margin;
4. Bleeding index- severity of the gingival inflammation, measured by the amount of bleeding observed during probing. There are several indices to measure bleeding. Each system is based on the principle that healthy gingival do not bleed;
5. The periodontal pocket which increases with the severity periodontal disease causing the normal gingival sulcus to become deeper than normal (a normal sulcus is 3 mm or less);
6. Bone level - Bone density tests, radiographs and probing measurements will be employed in assessing bone level and indicated on all patients’ charts. Radiographs detect:
a) Inter-proximal bone loss;
b) Changes in the bone as treatment progresses;
c) The crown to tooth ratio (the length of the clinical crown compared to the length of the root of the tooth); and
d) Signs of traumatic occlusion.
The applied classic periodontal treatment consists of the following steps:
- Local and general anti-inflammatory prophylaxis;
- Elimination of acute complaints e.g. pain, mastication problems and edema;
- Rehabilitation and rebalancing of the occlusal plane;
- Periodontium and bone nutrition;
- Amelioration of risk factors.
The surgical protocol consists of sub-gingival curettage that involves scraping or cleaning the gingival lining of the pockets with a sharp curette to remove necrotic tissue from the pocket wall. The periodontal surgery provides access to the root surface, allows removal of the infected tissue as well as the addition of nutrition directly to the bone by applying local collagen, hydroxyl-apatite, bone grafts, enzymes or antibiotics. After the surgical intervention, anti-inflammatory treatment will continue daily. Patients will be monitored at regular intervals over the course of 2 years.
For the LLLT we conceived an irradiation protocol following the data in the literature, and our experience. In general we will use an infrared diode laser type BF (EN 60 601-1), class 3B, safety class 1, with two laser beams, one infrared with a wave length = 810 nm, and another beam with a wave length = 660 nm. Convergent beams with energy between 0.5 and 3J/cm2, will be applied continuously or in pulsed mode. The parameters will be adjusted depending upon the required penetration depth (2.5 – 12 mm).
LLLT will begin immediately after surgical curettage, when we will apply laser irradiation to the bone, through the inter-dental space, without contacting the surgical plague at a dosage of 0.5 J/cm2 per application, in pulsed mode. Before the suture, we will irradiate the external plane, scanning the maxillary area by contacting the skin with a dosage of 2 J/cm2. Thirty minutes after the suture, we will apply 1–4 J/cm2 to each hemi-arcade area, the total dose being 4–16 J/cm2.
In the first three days after the surgery, we will irradiate the external plane with the same dose daily. In acute forms, we will apply a dose of 4J/cm2 every two days for the first week, two sessions in the second week, and one session in the third week. In the following six months, we plan to apply one irradiation session monthly, at the same dose. In chronic cases, the treatment will be comprised of additional irradiation sessions, at smaller doses, over a longer period of time.
LLLT will be repeated every six months together with conventional periodontal disease prophylaxis and nutritional support of the immune system. We will evaluate the results by x-ray after one month, three months, six months and afterwards, every six months over the course of two years.
4. STUDY DEVICE
For this study we will use an FDA cleared LLLT system developed by Thor Inc. The light intensities and exposure times are within safety limits as set by the American National Standard Institute (ANSI) and recommended by the Occupational and Safety & Health Administration (OSHA) of the US Department of Labor. According to these standards (see ANSI Z136.1-2000, page 48, Table 7, entry for Visible and Near-Infrared light) the maximum permissible exposure (MPE) before any tissue damage occurs is given by MPE = 200x10^[0.002(700)] mW/cm2, where is the wavelength of the light. For example, at = 810 nm the MPE = 316 mW/cm2, which is more than 10 times the intensities used in this study. Therefore, no adverse effects on the exposed tissues are expected.
We use a Thor infrared diode laser type BF (EN 60 601-1), class 3B, safety class 1, with two beams -one infrared, with a wave length = 810 nm, and one red, with a wave length = 660 nm. The convergent beams will produce energy between 0.5 and 3 J, to be applied continuously or in a pulsed mode. The parameters will be adjusted to achieve penetration depths from 2.5 up to 12 mm. to blind the study we will be using two laser devices. One will be active and one will be inactive. The inactive device will have a guided light that simulates the active ray. To make sure that the trial is double-blind neither the operator nor the subject will know which device is used. Only one member of the team, Prof. Hielscher, will know which patients have been treated with the active laser and which with the placebo.
5. STUDY SUBJECTS
To participate in this study, subjects must be diagnosed with Advanced Chronic Periodontitis. Additionally, study subjects will be screened to include patients with diabetes, with osteoporosis as well as subjects that have Advance Chronic Periodontitis by local factors only. The subjects will be diagnosed based on the status of the disease at the baseline. Furthermore, blood tests, bone density and local tests will proceed to both the control group and experimental group.
We will recruit approximately 200 subjects with Advanced Chronic Periodontal Disease. In all cases, the primary physician of the patient will diagnose and supervise the treatment and have to agree that the patient is suitable for the study and ascertain from the patient that he/she is willing to discuss the study with the research team before any approach may be attempted by the investigators.
There will be no restrictions based on gender, race or age, however only adult patients over age 18 will be recruited. We anticipate recruiting women and minorities in proportion to the demographic makeup of patients with ACP seeking treatment at the Dental Clinic of the Columbia University Medical Center.
7. CONFIDENTIALLITY OF STUDY DATA
All study data will be coded according to the order and the date a patient participated in the study The data will be stored on a computer workstation. The computer and data are only accessible by the Principal Investigator and co-investigators. The PI will maintain a master list that links human subject names to the particular data, on a separate storage device located in the office. No other persons will have access to that information.
8. POTENTIAL RISKS
The LLLT performed in this study presents no known hazards. Unlike x-rays, the energy from light sources employed in this study is non-ionizing; the tissue will not be damaged. The light intensities and exposure times will be within limits set by the American National Standard Institute (ANSI) and recommended by the Occupational and Safety & Health Administration (OSHA) of the US Department of Labor. According to these standards the maximum permissible exposure (MPE) before any tissue damage occurs is given by MPE = 200x10^[0.002(l660, l810)] mW/cm2, where l is the wavelength of the light used in the study (see ANSI Z136.1-2000, page 48, Table 7, entry for Visible and Near-Infrared light). For example at l = 810 nm, a typical wavelength to be used in the study, the MPE = 316 mW/cm2, which is at least 10 times less than the maximum permitted dosage. No adverse effects on the tissue exposed to light are thus expected. All operator personnel and study subjects are to wear protective goggles while exposed to the LLLT devise to avoid accidental eye exposure.
9. POTENTIAL BENEFITS
Participating subjects will benefit from the classic modern and complete dental treatment of their periodontal disease. We expect that patients treated in addition with LLLT will further benefit from improved healing times, less pain, less bleeding, less post surgery complications such as edema, inflammation, and infection.
General social benefits are to be expected if the study leads to the development of a novel LLLT modality for treatment of periodontal disease, which allows for early noninvasive treatment of periodontal infection. The optical technology promises to be more cost effective and may reduce the cost of patient care.
The LLLT is offered to enhance standard clinical methods in the treatment of periodontal disease. The alternative to participating in this study is simply not to participate.