|Diabetics and Periodontal Disease|
LOW LEVEL LASER THERAPY IN THE TREATMENT OF PERIODONTAL DISEASEA COMPARE STUDY DIABETICS, OSTEOPOROTIC PATIENTS, HEPATIC DISEASE PATIENTS AND HEALTHY ONES
Dana Vieru DDS, MS, PhD (1,2), Martha Cortez DDS (3), Lewis Clayman MD, DDS (4), and Anca Silvia Dumitriu DDS, MS, PhD, (1)
The general objective of this study was 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 and attacks the structures of the periodontium (the ligaments around the tooth), the epithelial attachment, the gingivae, epithelial attachment, cementum that cover the root of the tooth, and the alveolar bone that support the tooth. 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.(22) There is evidence that LLLT has an anti-inflammatory agent, and stimulates collagen and bone growth. Over the last decade, much progress has been made in elucidating the underlying principles. Approximately half of the diabetic patients and half of the patients with osteoporosis received LLLT in addition to the classical treatment. In this study we search for 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. For all four groups [(1) diabetic patients treated with LLLT ; (2) diabetic patients without LLLT; (3) osteoporotic patients treated with LLLT ; and (4) osteoporotic patients without LLLT we determined the mean and standard deviations of the following parameters: gingival bleeding time, pain relief time, bone recovery time inflammation, complete healing. The LLLT-treated groups were superior to the non-treated control groups in both the diabetic and osteoporotic patients. General social patient’s benefits are the development of a novel LLLT modality for treatment of periodontal infection. LLLT technology promises to become even more cost effective and may reduce the cost of patient care.
Periodontal disease is an infectious process that is the leading cause of tooth loss in adults. (1) 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 support the tooth. Periodontal disease causes a breakdown of the periodontium, resulting in loss of the tissue attachment and destruction of the alveolar bone.
Almost 75% of all adults have some form of periodontal disease, and most are unaware of the condition. Certain systemic conditions increase the patient’s susceptibility
to certain other 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 crowns, orthodontic appliances or partial dentures may also contribute to the progression of the periodontal disease as well as smoking. Further more, 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 condition, diabetes osteoporosis, metabolic calcium dysfunction, immune system deficiency and stress.
Diabetes mellitus is a strong risk factor for periodontal disease. Diabetic individual are 3 times more likely to have attachment and bone loss than non-diabetic patients. Furthermore, osteoporosis is a reduction of total skeletal mass due to increased bone resorption, which results in predisposition to pathologic fractures and with alveolar bone loss. It is common especially in thin, elderly, white women and young men working in difficult (in cold, over night). It is caused by calcium or hormone (estrogen)deficiensies over a long period of time. The treatment includes estrogen therapy, calcium supliments and vitamin D. 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 short term effect on the periodontium. At the same time, they have a very toxic effect on the liver, which toxicity had 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 development of the first lasers in the early sixties, there was evidence that laser irradiation could result in modulation (stimulation or inhibition) of biological processes. (2) At the beginning, what became known as Low Level Laser Therapy (LLLT) was empiric; it was not based on vitro studies, so that the interaction mechanisms between the laser beam and living matter were at first unknown. This empiric character of the empirical investigations lasted for quite some time, especially because the most medical laser users did not fully understood the principal of lasers, the characteristics of the laser beam, and the interaction mechanisms. (3)
LLLT was originally defined as application of laser light with an intensity of lass than 250 mW / cm2, to treat various medical conditions. In fact much stronger power densities, up to around 5 W/cm2 , have been proved to deliver therapeutic effects that imply no heat or mechanical traumatic actions to the target tissue. Over the last 30 years, laser therapy as distinct to laser surgery has been successfully applied to wound healing, pain management, for diabetics, in physiotherapy, dermatology, gynecology and dentistry. There is evidence that LLLT has a antibacterial effect, acts as a anti-inflammatory agent and stimulates collagen and bone growth. ( 4-9 ). Over the last 2 decades, much progress has been made in elucidating the underlying principles. ( 10-12 )
The light is scattered in tissue in 3 possible manners. 1. Volumes of partially polarize light are formed, 2. Points of high light intensity appear, and 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 stimulate the creation of oxygen that leads to the formation of ATP, and stimulates cAMP and enzymes. Triggered immunological chain reactions occur. Macrophages are activated. The number of mast cells is increased together with accelerated granulation namely processes that lead to anti-inflammatory actions and pro-collagen synthesis in fibroblasts, is enhanced, leading in tandem with some of the earlier reactions to regeneration of the tissue and healing.(13-15)
When pointes 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, and K, and the sodium-potassium, and sodium-calcium pumps are stimulated into action. The receptor activity on cell membrane increases well as the serotonin level in blood. At the same time, LLLT stimulates the synthesis of endorphins, decreases C-fiber activity and, in the areas of high intensity levels, increases, nerve cell action potentials (8). All these mechanisms influence the pain and anti-inflammatory processes. (16-19)
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. The symptoms of periodontitis are a red, swollen, tender gingival, bleeding while brushing, flossing or spontaneous, loose or separating teeth, pain or pressure when chewing, pus around the teeth or gingival tissues. We sought to compare the effects of LLLT on examples of advanced chronic periodontitis that have caused severe destruction of the periodontitis that have caused severe destruction of the periodontal structures, i.e. clinical attachment loss over 5 mm, increased bone loss, increased tooth mobility with the same conditions untreated with LLLT in patients complicated with diabetics and osteoporosis.
Subjects and Methods
To participate in this study had to have a confirmed diagnosis of advanced chronic periodontitis. Additionally, study subjects were screened to include patients with diabetes hepatic disorders, osteoporosis as well as healthy individuals that had advance chronic periodontitis by local factor only. The subjects were diagnosed based on the status of the disease at the baseline. Furthermore, blood tests, bone density at the baseline. Furthermore, blood tests, bone density and local tests were performed on both the control group and experimental group. There was no restriction for reenrollment based on gender, race or age, however only adult patients over the age of 18 were recruited.
The addition of LLLT in the treatment group was offered to enhance standard clinical methods in the treatment of periodontal disease. The alternative to participating in this study is simply not to participate. All subjects, having had the purpose and methods of the trial explained to them, signed forms og informed consent before being recruited into the study. The study was conducted under the precepts of the Geneva Convention and was approved by the relevant Ethics Committee.
We recruited approximately 200 patients (diagnosed with either diabetics, osteoporosis, hepatic disorder and local factors healthy subjects) evidencing marginally advanced chronic periodontitis. A correct diagnosis was assessed based upon the medical and dental history. All of these patients received classic modern treatment. Approximately half of the diabetic patients and half of the patients with osteoporosis received LLLT in addition to the classical treatment. The number of patients enrolled was determined by statistical power calculations using the data obtained in our earlier pilot studies. Patients were randomly assigned to 8 groups.
In the control group:
A. Healthy (24 with LLLT, respectively 10 without),
B. with toxic pathology concerning hepatic and renal diseases (18 with LLLT and 10 without);
C. with nutrition pathology – diabetes (12 with LLLT and 14 without);
D. with calcium metabolism related disorders (14 with LLLT and 8 without).
In the laser therapy group:
A.10 patients were young healthy people, 14 were mature healthy people,
B.8 patients were young and 10 were mature, all with hepatic and renal toxicity
C. For the diabetics, 4 subjects were young and 8 mature.
D. Subjects with calcium problems which received LLLT: 6 young and 8 mature
(1) diabetic patients treated with LLLT, (2) diabetic patients without LLLT,(3) osteoporotic patients treated with LLLT, (4) osteoporotic patient treated without LLLT, (5) hepatic disease patients treated with LLLT, (6) hepatic disease patients treated without LLLT, (7) local factor health patient treated with LLLT (8) local factor health patient treated without LLLT.
For all 8 groups we determined the mean and standard deviations of the following 6 parameters: 1. gingival pleading time, 2. pain relief time, 3. bone recovery time, 4. inflammation; 5. complete healing; and 6 Recurrence. The parameters are qualified as follows:
For each subject participating in this study a complete detailed history and diagnostic evaluation was performed, based on the dental and medical history. The periodontal examination included the assessment of:
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 classic periodontal treatment as applied to all patients in both the LLLT and the no-LLLT groups consisted 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, and amelioration of risk factors.
The surgical protocol consisted of sub-gingival curettage that involved scraping or cleaning the gingival lining of the pockets with sharp curette to remove necrotic tissue from the pocket wall. Periodontal surgery provided access to the infected tissue from the pocket wall. Periodontal surgery provide access to the root surface, and allow 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 usually continued daily. Patients were 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 used an infrared diode laser type BF (EN60 601-1), class 3B, safety class 1, with two laser beams, one infrared with the wavelength of 810 nm and another visible red beam with the wavelength of 630 nm. Convergent beams with energy between 0.5 and 3 J/ cm2, were applied continuously or in pulsed mode. The parameters were adjusted depending upon the required penetration depth (2.5 – 12 mm).
LLLT begin immediately after surgical curettage when we applied laser irradiation to the bone, though the inter-dental space, without contacting the surgical plaque at a dosage of 0.5 J/cm2 per application, in the pulsed mode. Before the suture, we irradiated the pulsed mode. Before the suture, we irradiated the external plane, scanning the maxillary area by treating the skin with a dosage of 2 J/cm2.Thirty minutes after suturing, usually applied 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 irradiated the external plane with the same dose daily. In acute forms, we usually applied 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 planned to apply one irradiation session monthly, at the same dose. In chronic cases, the treatment comprised additional irradiation sessions, at smaller doses, over a longer period of time.
LLLT was repeated every six months together with conventional periodontal disease prophylaxis and nutritional support of the immune system. We evaluated the results by x-ray after on month, three months, six months and every six months thereafter over the course of two years.
The promising results of earlier pilot studies provided the impetus for the proposed 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 results in shorter pain recovery time, bleeding and reduced post surgery complications (edema, inflammation, infection) faster formation and maintenance of the mastication functions.
There findings were corroborated in the present study. Looking first at the post-surgical pain, Fig.1 shows the time taken for complete pain relief (in hours) comparing the LLLT-treated and classic treatment only groups, broken down between the osteoporotic and diabetic patients. These was a significant difference in the pain relief time between the two treatment groups, with the average time taken to no pain post surgery for the LLLT and control groups of 3.75 hr and 11.9 hr respectively. We also noted analgesic requirements of two treatment groups, and the LLLT group required on average 65%less analgesics than the control group (data not shown).
Fig. 2 shows the time in month for the bone recovery to occur, compared between treatment and disease groups. Full recovery was noted at an average of 31.75 months for the control group and 16.45 months for the LLLT group, almost twice as quickly for the latter. There was a difference between disease groups, although not statistically significant, whereby recovery tended to be longer in the osteoporotic groups, although not statistically significant, whereby recovery tended to be longer in the osteoporotic groups for both treatment groups.
Bleeding stopped significantly faster post-surgery in the LLLT compared with the control group (Fig. 3), 558.5 seconds on average for the latter compared with 117.8 sec for the former. A slightly longer time was required in the diabetic patients compared with the osteoporotic patients, but without statistical significance.
Fig. 4 to 7 show typical pre- intra- and immediately postoperative stages in a patient with periodontal disease from the LLLT-treated group. Immediately post-treatment, we notice gingival hyperplasia has been removed, with a healthy-looking gingiva and teeth.
Radiographic findings showed better bone recovery at the LLLT than in the control group, as seen in Fig. 8a, b. These typical pretreatment findings showed major resorption of the teeth in the middle of the image, with poor radio-opacity of the bone, suggesting higher bone mineral density in this osteoporotic 48 years-old patient.
In short, in all LLLT-treated patients compared with the classic-only treatment group we noted less and faster-resolved postoperative pain, quicker bleeding control,
improved healing of the soft tissue, rapid recovery of a more compact bone tissue, rapid recovery of a more compact bone tissue restoring stability to the teeth, and good maintenance and improvement of both the masticatory and esthetic functions, with healthier gingival tissue. In particular, very good results were obtained in diabetics for whom wound healing is normally compromised. Otherwise there were no statistically differences between the disease-grouped patients Recurrence was limited in both groups, but was noticeably lower in the LLLT-treated group.
Overall we did note that the effectiveness of LLLT varied somewhat as a function of the age, general health and metabolic problems of the patient (specific data not shown). This must be addressed in a future study with better patient stratification according to these aspects.
In the entire experimental group subjects, laser therapy association with the classic therapy gave overall better and longer – lasting results than in the control group who received classic therapy alone. This is in agreement with previous studies from ourselves and others in the field of LLLT in orthodontics. (1, 18, 20) Immediate and short-term effects were as follows: evolution of the wound without bleeding, no post surgery complications such as edema, inflammation, infection, and pain, with quick formation of the clot in the wound and good maintenance of it: good biological repair over a shorter period than without LLLT; maintenance and then improvement of the masticatory functions; and a good aesthetic appearance with no post surgery alterations, permitting the patient to continue their work and social lives without interruption.
Long term effects were: rapid healing with excellent cosmetic aspect, healing of the soft tissue, with the fixation of the teeth, with the recovery of more compact and radio-opaque alveolar bone tissue, thus restoring the masticator and esthetic functions, and maintaining them. Gingival tissue looked healthy with a firm aspect, and mobility
of individual teeth in their sockets disappeared. We and others have previously reported on the re-growth of absorptive alveolar bone in this aspect, (1, 20) and at a molecular level the photo-activation effect of near infrared laser energy on the up-regulation of expression of the gene in the oral osteoblasts responsible for switching on bone production (FOF1-ATPase subunit-b) has also been shown.(21)
For the diabetic patient group, we found that LLLT was efficient in its anti-inflammatory treatment so the healing was more secure and rapid than in the non radiated group, classic treatment only group: we must note here that this observation in connected only with the gingival and the periodontal disease, on which the present study was based and where and where we did our measurements, and showed a tendency rather than a statistically significant difference. From the important aspect of safety and efficacy, there was a lower percentage in the LLLT-treated group, and we did not have a single patient in whom the laser therapy was seen to have any adverse effects.
From our data LLLT performed in this study presented no known hazards. Unlike x-rays, the energy from light sources employed in this study was non-ionizing, non-accumulative and was incapable of damaging the target or adjacent tissue. The light intensities and exposure times were 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. LLLT system have been cleared for marketing by FDA through the Premarket Notification/510 (k) process as adjunctive for the temporary relief of pain, and are non-significant risk Class II medical devices which may be distributed in the U.S. to individual practitioner who have approval from an Institutional Review Board (IRB) for the investigational clinical use of the device.
According to these standards the maximum permissible exposure (MPE) before any tissue damage occurs is given by MPE = 200x10y [0.002 (lambda)] mW/cm2, where lambda is the wavelength of the light used in the study in nm (see ANSI Z136.1-2000, page 48, Table 7, entry for Visible and Near-Infrared light). For example at lambda = 810 nm and 660 nm, the wavelength used in the study, the incident intensities were at least 10 times less than the maximum permitted exposure. No adverse effects on the tissue exposed on the tissue exposed to light were thus expected. In addition, to avoid accidental optical hazards, all operator personnel and study subjects wore mandatory protective goggles of an appropriate wavelength-related optical density while exposed to the LLLT device.
All participating subjects benefits from the classic modern and complete dental treatment of their periodontal disease. Patients treated in addition with LLLT further benefited from improved healing times, less pain, less bleeding, less post surgery complications such as edema, inflammation, and infection compared with the classic treatment only group.
General social benefits are the development of novel and inexpensive LLLT modality for treatment of periodontal disease, which allows for early noninvasive treatment of periodontal infection. LLLT technology promises to be more cost effective and may reduce the cost of patient care, while improving the good results already achieved by meticulous classic periodontal intervention.
The authors would like to express their special gratitude to Prof. Andreas Hielsher PhD and Prof. Dr. Eugenia Kovacs for their invaluable advice and support.