Marco Mozzati

Effect of Low-Level Laser Irradiation on Bisphosphonate-Induced Osteonecrosis of the Jaws: Preliminary Results of a Prospective Study

OBJECTIVE The aim of this study was to detail the clinical efficacy of low-level laser therapy (LLLT) for the management of bisphosphonate-induced osteonecrosis of the jaws (ONJ-BP). BACKGROUND ONJ-BP is the correct term, recently emerged, to describe a significant complication in a subset of patients receiving drugs such as zoledronic acid, pamidronate, and alendronate. No definitive standard of care has been set for ONJ-BP and no definitively agreed guidelines have been provided. There is currently no consensus on the correct approach to the issue. MATERIALS AND METHODS The investigators studied a prospective cohort of 20 patients affected by ONJ-BP, who received biostimulation with a pulsed diode laser (GaAs). Patients were exposed to a 904-nm infrared laser (50 kHz, 28.4 J/cm(2) energy density, 40% duty cycle, spot size 0.8 cm). Outcome variables were the size of lesions, edema, visual analogue score of pain, presence of pus, fistulas, and halitosis. Preoperative results were compared with the postoperative outcome and statistically evaluated. RESULTS Four weeks after LLLT, a statistically significant difference was observed for reported pain (p = 0.0001), clinical size (p = 0.0034), edema (p = 0.0005), and presence of pus and fistulas (p = 0.0078 and p = 0.03, respectively). CONCLUSION This study suggests that LLLT would appear to be a promising modality of treatment for patients with ONJ-BP, providing that clinical efficacy is safe and well tolerated, especially by those patients who require conservative treatment. Of course, this needs to be addressed further in larger and randomly controlled studies in different clinical settings.

Treatment outcomes in patients with bisphosphonate-related osteonecrosis of the jaws: a prospective study

OBJECTIVES The aim of this study was to evaluate the 2-year success rate of management of patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ). STUDY DESIGN A prospective study was performed. Positive outcome variables were the resolution of symptoms and the status of the mucosa. RESULTS A total of 37 patients are described. The precipitating event was a dental extraction in 22 cases (59.5%). Thirteen patients (35.1%) underwent surgery, and 24 (64.9%) underwent antimicrobial therapy alone. After 2 years, 20 patients (54.1%) presented with soft tissue closure over previously exposed bone, and there were no statistical differences in gender, age, bisphosphonate treatment, or treatment modalities. Spontaneous lesions seemed to have a worse prognosis (P = .001). CONCLUSIONS Initial antimicrobial treatment, and later surgery for unresponsive patients, might be a feasible treatment modality for BRONJ. Because these results are not conclusive, it would be very interesting to know if this statement would be the same with a greater number of patients.

Platelet-rich therapies in the treatment of intravenous bisphosphonate-related osteonecrosis of the jaw: a report of 32 cases.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an important complication in cancer patients taking intravenous BPs (BPs). In most cases, BRONJ is associated with an oral surgery procedure involving jaw bone. Currently, BRONJ management remains controversial, and there is no definitive standard of care for this disease. In fact, several articles in the recent literature discuss treatments that range from topical to surgical treatment, without definitive conclusion about treatment. A clinical study was conducted on 32 patients treated with i.v BPs for oncologic pathologies affected by BRONJ. The patients were treated by resection of the necrotic bone with primary closure of the mucosa over the bony defect using plasma rich in growth factors (PRGF). Orthopanoramic and computed tomography were performed before and after surgery. No intraoperative complications were observed, and all 32 cases were treated successfully. Our data on the use of PRGF demonstrate positive results for this surgical treatment. PRGF may enhance vascularization and regeneration of osseous and epithelial tissues.

Superpulsed Laser Irradiation Increases Osteoblast Activity Via Modulation of Bone Morphogenetic Factors

Laser therapy is a new approach applicable in different medical fields when bone loss occurs, including orthopedics and dentistry. It has also been used to induce soft‐tissue healing, for pain relief, bone, and nerve regeneration. With regard to bone synthesis, laser exposure has been shown to increase osteoblast activity and decrease osteoclast number, by inducing alkaline phosphatase (ALP), osteopontin, and bone sialoprotein expression. Studies have investigated the effects of continuous or pulsed laser irradiation, but no data are yet available on the properties of superpulsed laser irradiation. This study thus aimed to investigate the effect of superpulsed laser irradiation on osteogenic activity of human osteoblast‐like cells, paying particular attention to investigating the molecular mechanisms underlying the effects of this type of laser radiation.

Effect of Low-Level Laser Irradiation on Unresponsive Oral Lichen Planus: Early Preliminary Results in 13 Patients

OBJECTIVE To detail the efficacy of low-level laser therapy (LLLT) for the management of oral lichen planus (OLP) unresponsive to standard therapy. BACKGROUND OLP is an inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empiric. However, to date, the most commonly used and useful agents for the treatment of OLP are topical corticosteroids. MATERIALS AND METHODS The investigators studied a prospective cohort of 13 patients affected by OLP, who received biostimulation with a pulsed diode laser (GaAs). Patients were exposed to a 904-nm pulsed infrared laser (4 J/cm(2) energy density per minute; spot size, 0.8 cm). Outcome variables, statistically evaluated, were as follows: the size of lesions, visual analogue score of pain, and stability of the obtained result in the follow-up period. RESULTS We detailed significant reduction in lesion size and in reported pain. No reported complications or therapy side effects were observed in any of the patients treated. CONCLUSION This study suggests that LLLT could be a possible treatment for patients with unresponsive OLP. These results, although not conclusive, are a step forward for enhanced management of this quite common condition; however, it would be interesting to the results would be the same with a greater number of patients or in a different clinical setting.

The impact of plasma rich in growth factors on clinical and biological factors involved in healing processes after third molar extraction

Extraction of an impacted mandibular third molar is a common surgical procedure, although it still leads to several postoperative symptoms and complications. The study assessed the efficacy of autologous plasma rich in growth factors (PRGF) in the healing process by checking the difference of tissue cytokines and other healing factors produced by the mucosa after extraction between sites treated with PRGF and control sites and, at the same time, by evaluating the clinical efficacy of PRGF in terms of reduced pain and facial swelling. This study was a split-mouth study, in which the patient becomes his/her own control, to eliminate any individual response differences toward PRGF treatment. The parameters regarding inflammation and subsequent wound healing were all significantly higher at PRGF sites than at control sites. The increase at PRGF sites of the two proinflammatory cytokines evaluated, interleukin (IL)-1β and IL-6, was accompanied by the increase of two anti-inflammatory cytokines, IL-10 and transforming growth factor-β. Furthermore, IL-1β and IL-6 induce fibroblast and keratinocyte proliferation, important events in wound healing. Postoperative pain and the swelling, measured at all experimental times, were reduced in the presence of PRGF.

Autologous platelet concentrates for bisphosphonate-related osteonecrosis of the jaw treatment and prevention. A systematic review of the literature

PURPOSE Bisphosphonate related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction consisting of progressive bone destruction in the maxillofacial region of patients under current or previous treatment with a bisphosphonate. Autologous platelet concentrates (APC) demonstrated to enhance bone and soft tissue healing in oral surgery procedures. The present systematic review aimed at evaluating if APC may improve treatment and prevention of BRONJ in patients under bisphosphonate therapy. METHODS MEDLINE, Scopus and Cochrane databases were searched using terms like bisphosphonates, osteonecrosis, BRONJ, platelet concentrate, PRP, PRF, PRGF. No language, publication date and study design limitation was set. A hand search of the bibliographies of identified articles was also performed. The primary outcome was recurrence/onset of BRONJ after oral surgery procedures. RESULTS Eighteen studies were included, reporting on 362 patients undergoing oral surgery in combination with APC. The adjunct of APC in BRONJ treatment significantly reduced osteonecrosis recurrence with respect to control. APC was associated with a lower BRONJ incidence after tooth extraction, though not significant. Heterogeneity was found regarding bisphosphonate type, clinical indication, treatment duration, triggering factors, study design, follow-up duration, type of APC, outcomes adopted to evaluate treatment success. CONCLUSION Though the results of this review must be cautiously interpreted, due to the low evidence level of the studies included, and the limited sample size, they are suggestive of possible benefits of APC when associated with surgical procedures for treatment or prevention of BRONJ. To confirm such indication, prospective comparative studies with a large sample size are urgently needed.

Tooth extraction in patients on zoledronic acid therapy

OBJECTIVES Surgical management of patients following zoledronic acid therapy is particularly difficult, since the dental extraction is the main cause of BRONJ. METHODS A case-control study was conducted on 176 patients treated with intravenous (IV) bisphosphonates for oncologic pathologies who also underwent dental extractions. The study was divided randomly into two groups: 91 were treated with Plasma Rich in Growth Factor Plasma (PRGF) (study group) and the other 85 were not treated with the growth factor preparation (control group). RESULTS Panoramic X-ray and computed tomography were performed both before and 60 months after surgery. By clinical and radiological diagnosis, BRONJ was diagnosed in only 5 patients in the control group at an average of 91, 6 days after tooth extraction. CONCLUSIONS We hypothesize that Plasma Rich in Growth Factor (PRGF) is important for the successful treatment of patients on bisphosphonates to restore the osteoblast/osteoclast homeostatic cycles via autologous cytokines. Moreover, this protocol reduces the risk of BRONJ when it is necessary to perform dental extractions in patients undergoing IV bisphosphonate treatment.

Influence of the thickness of the resin palatal vault on the closest speaking space with complete dentures.

The closest speaking space (CSS) has been considered stable over time, and therefore useful to determine the vertical dimension of occlusion (VDO) in edentulous patients. Clemençon affirms that, in complete denture wearers, CSS is not constant but depends on the thickness of the resin palatal vault, and that is the air volume needed to pronounce words to remain constant. The aim of this study was to evaluate Clemençon hypothesis in a group of edentulous patients rehabilitated with traditional maxillary denture and mandibular implant anchored overdenture. The CSS was determined by means of a kinematics method using the Elite System(R) at 30, 60, 90, 180, 360 days from delivery. The CSS was assessed twice at each stage: with the unmodified denture and a second time after thickening the resin palatal vault by 2 mm with a calibrated wax layer. The CSS after thickening the resin palatal vault was wider. The wider CSS observed can be because of oro-sensory feedback excited by contact between tongue and palatal vault. As hypothesized by Clemençon thickening the resin palatal vault could be a useful procedure to increase the VDO, in cases in which it is too low from the aesthetic stand point.

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid

ObjectivesThe intravenous injection of bisphosphonates, currently used as treatment for osteoporosis, bone Paget’s disease, multiple myeloma, or bone metastases, can cause jaw bone necrosis especially in consequence of trauma. The present research aimed to clarify the mechanisms underlying bone necrosis, exploring involvement of the oral mucosa “in vivo.”Patients and methodsSpecimens of oral mucosa were removed from bisphosphonate-treated patients with or without jaw bone necrosis. In mucosa specimens, expression was evaluated of: cytokines involved in the inflammatory process, factors involved in osteoclast activity, i.e., receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin, a factor involved in cell proliferation, namely hydroxymethylglutaryl coenzyme A reductase, and a factor involved in angiogenesis, namely vascular endothelial growth factor (VEGF).ResultsInterleukin (IL)-6 and the RANK/osteoprotegerin ratio were significantly elevated in mucosa from patients with versus without jaw necrosis, whereas hydroxymethylglutaryl coenzyme A reductase and VEGF were significantly decreased.ConclusionsOur results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. In turn, IL-6 stimulates osteoclast activity, as shown by the increased RANKL/osteoprotegerin ratio.Clinical relevanceThe results of this study suggest the importance of evaluating during bisphosphonate treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to monitor the jaw osteonecrosis onset. To avoid repeated mucosa excisions, the determination of these factors could be carried out in crevicular fluid.