OZONE THERAPY AND BISPHOSPHONATES-RELATED OSTEONECROSIS OF THE JAWS
Date: 05/26/2011
Bisphosphonates (BP) are
molecules that have been used for years to treat or to prevent bone
disorders such as skeletal complications in patients with multiple
myeloma, osteolytic bone metastases of solid tumors, or from
diseases such as osteoporosis and osteometaboliche Paget's disease.
Bisphosphonates are structural analogues of inorganic pyrophosphate
and act by blocking the action of osteoclasts. The increasing use
of BP, is related to the increased number of cases which associates
the recruitment of these molecules with the onset of a serious
adverse event such as jaw osteonecrosis (ONJ). The first case of
ONJ-bisphosphonate (BRONJ) was described by Marx et al in 2003 that
defines the disease as a jawbone necrosis resistant to conventional
therapy for more than 8 weeks, affecting patients undergoing
treatment with BP Radiotherapy of the mandible (1.2). Because of
complications such as intractable pain, difficulty in feeding,
sinus infections, onset of abscesses or fistulas in the oral soft
tissues, the Bronja is considered a disease that can damage
significantly the quality of life of patients.
The risk of ONJ in patients treated with intravenous BP is very high (1-12%), while after oral intake, the risk is low (0:01 to 00:04%) (1).
Nowadays the causes which increase the risk of occurrence and consequently the necessary steps to minimize it are still unknow. Over the years, due to the increase of this adverse event, CHMP of EMA has drawn , following a review on the risk of ONJ associated with the use of BP, an official statement (EMA/CHMP/292475/2009) to inform that "an increased risk of osteonecrosis of the jaw in patients taking these drugs ....". A review about 138 articles (about 1600 patients) showed that women are more affected than men (61% vs. 39%), the disease has mainly mandibular localization (65%; maxilla only 27%), occurs in 88% of patients receiving intravenous therapy and in 12% of those on oral therapy.
The active principles more involved in the onset of BRONJ are alendronate taken orally (77%) and zelodronato administered intravenously (53%).
Although the major risk factors associated with the onset of BRONJ are the power of bisphosphonates, the dose and mode of administration, there are other causes such as gender, genetic factors, smoking, dental extractions and implants from bedsores. Other risk factors that may influence the occurrence of outbreaks are kidney failure, diabetes, obesity, vascular disease, the periodontal disease, steroids and drugs antineoangiogenetici. In the last few years, the experts have noted that one of the triggering events BRONJ may be the surgical procedures such as dental extractions.
BRONJ therapy is still an open problem because there are no scientific evidence-based guidelines. Scientific bibliografy hasn't reported unequivocally effective treatments and the therapy's discontinuation with BP does not lead to healing. The two main therapeutic approaches for the treatment of this disease are the antibiotic therapy and surgery. The latter is recommended only for patients with Stage III (65% of interventions are conservative and only 35% highly demolition) that hardly respond appropriately. With regard to antibiotics, whose intake is shown in stages I and II, the most widely prescribed are aminopenicilline (39%), combination of beta-lactamase inhibitor and aminopenicillina (28%), metossipenicillina (26%). These therapies usually follow a second course of antibiotic treatment with other antimicrobials treatment such as clindamycin, tetracycline, and fluoroquinolones (3).
The scientific bibliografy doesn't have sufficient studies in which patients were subjected to experimental procedures, therapeutic alternatives such as hyperbaric oxygen therapy, applied in the platelet-rich plasma, laser biostimulation. As far as the ozone therapy, it is important to note however, that ozone is used by dentists and physicians from around one hundred years for a variety of indications including the treatment of dental caries. Ozone has a positive effect both on the soft tissues and bone through the stimulation of endogenous antioxidants and blocking the pathway of xanthine / xanthine oxidase to generate oxygen free radicals.
Ozone also increases the concentration of red blood cells and hemoglobin and stimulates diapedesis and phagocytosis of the reticulo istocitario.
Pre-clinical studies performed in animals suffering from parondontopatie treated with infusion of ozone in situ, have given positive results and the results showed not only a reduction in inflammation, but also a complete resolution to bone (4).
It has also been shown in patients with multiple myeloma treated with BP, that ozone is able to increase both the benefits of surgery, both the antibiotic (5-8) when administered as a gas before and after dental surgery. Other authors have successfully used ozone therapy in patients with avascular necrosis of the jaw as the stimulating effect of ozone is a possible aid for a patient suffering from avascular necrosis also antibacterial and analgesic properties.
Finally, Ripamonti et al have proposed local applications (with silicone device) of ozonized oil associated with antibiotic therapy (9) the results are very encouraging.
The authors state that the result suggests that this technique can be an excellent noninvasive technique for the treatment of BRONJ. So compared to other unconventional approaches, ozone therapy has the advantage of having a useful flap in the management of areas osteonecrotic of surgical wounds or post-mining sites in patients with BP for the stimulation of cell proliferation and healing of soft tissue.
The risk of ONJ in patients treated with intravenous BP is very high (1-12%), while after oral intake, the risk is low (0:01 to 00:04%) (1).
Nowadays the causes which increase the risk of occurrence and consequently the necessary steps to minimize it are still unknow. Over the years, due to the increase of this adverse event, CHMP of EMA has drawn , following a review on the risk of ONJ associated with the use of BP, an official statement (EMA/CHMP/292475/2009) to inform that "an increased risk of osteonecrosis of the jaw in patients taking these drugs ....". A review about 138 articles (about 1600 patients) showed that women are more affected than men (61% vs. 39%), the disease has mainly mandibular localization (65%; maxilla only 27%), occurs in 88% of patients receiving intravenous therapy and in 12% of those on oral therapy.
The active principles more involved in the onset of BRONJ are alendronate taken orally (77%) and zelodronato administered intravenously (53%).
Although the major risk factors associated with the onset of BRONJ are the power of bisphosphonates, the dose and mode of administration, there are other causes such as gender, genetic factors, smoking, dental extractions and implants from bedsores. Other risk factors that may influence the occurrence of outbreaks are kidney failure, diabetes, obesity, vascular disease, the periodontal disease, steroids and drugs antineoangiogenetici. In the last few years, the experts have noted that one of the triggering events BRONJ may be the surgical procedures such as dental extractions.
BRONJ therapy is still an open problem because there are no scientific evidence-based guidelines. Scientific bibliografy hasn't reported unequivocally effective treatments and the therapy's discontinuation with BP does not lead to healing. The two main therapeutic approaches for the treatment of this disease are the antibiotic therapy and surgery. The latter is recommended only for patients with Stage III (65% of interventions are conservative and only 35% highly demolition) that hardly respond appropriately. With regard to antibiotics, whose intake is shown in stages I and II, the most widely prescribed are aminopenicilline (39%), combination of beta-lactamase inhibitor and aminopenicillina (28%), metossipenicillina (26%). These therapies usually follow a second course of antibiotic treatment with other antimicrobials treatment such as clindamycin, tetracycline, and fluoroquinolones (3).
The scientific bibliografy doesn't have sufficient studies in which patients were subjected to experimental procedures, therapeutic alternatives such as hyperbaric oxygen therapy, applied in the platelet-rich plasma, laser biostimulation. As far as the ozone therapy, it is important to note however, that ozone is used by dentists and physicians from around one hundred years for a variety of indications including the treatment of dental caries. Ozone has a positive effect both on the soft tissues and bone through the stimulation of endogenous antioxidants and blocking the pathway of xanthine / xanthine oxidase to generate oxygen free radicals.
Ozone also increases the concentration of red blood cells and hemoglobin and stimulates diapedesis and phagocytosis of the reticulo istocitario.
Pre-clinical studies performed in animals suffering from parondontopatie treated with infusion of ozone in situ, have given positive results and the results showed not only a reduction in inflammation, but also a complete resolution to bone (4).
It has also been shown in patients with multiple myeloma treated with BP, that ozone is able to increase both the benefits of surgery, both the antibiotic (5-8) when administered as a gas before and after dental surgery. Other authors have successfully used ozone therapy in patients with avascular necrosis of the jaw as the stimulating effect of ozone is a possible aid for a patient suffering from avascular necrosis also antibacterial and analgesic properties.
Finally, Ripamonti et al have proposed local applications (with silicone device) of ozonized oil associated with antibiotic therapy (9) the results are very encouraging.
The authors state that the result suggests that this technique can be an excellent noninvasive technique for the treatment of BRONJ. So compared to other unconventional approaches, ozone therapy has the advantage of having a useful flap in the management of areas osteonecrotic of surgical wounds or post-mining sites in patients with BP for the stimulation of cell proliferation and healing of soft tissue.
