**11. Photodynamic therapy and MRONJ**

There are various additional methods of treatment, in addition to surgical treatment, that promote healing of the lesion. For this purpose oxygen therapy (ozone, hyperbaric chamber), hormone therapy (parathyroid hormone), growth factor (**Figure 6**) therapy (PRP, PRF, PRGF, BMP), mesenchymal stem cell therapy and a combination of pantophilin and tocopherol [84–88] are used.

Vescovi et al. [89] in 2006 described the application of low-level-laser therapy (LLLT) as possible treatment of osteonecrosis of the jaw. The effect of lasers is classified in two categories, regarding its mW range: biostimulation (LLLT) and photodynamic therapy (PDT). Main difference between this two types is that in biostimulation therapy (LLLT) the laser acts directly on the tissue and aims to

**Figure 5.** *Surgical treatment- modeling of sharp sclerotic bone edges.*

**Figure 6.** *Augmentation using autologous growth factors; PRGF technique, F2 and F1 phase.*

*Application of Photodynamic Therapy in the Treatment of Osteonecrosis of the Jaw DOI: http://dx.doi.org/10.5772/intechopen.94257*

support tissue healing, while in photodynamic therapy (PDT) it acts on chemical medium (photosensitizer) (**Figure 7**) which induces cell (e.g. bacteria) and tissue damage as a chemical effect [90].

LLLT has from clinical point of view become adjuvant medical tool for enhancing wound-healing process, so some clinical studies reported laserinduced stimulation especially of soft tissue healing such as ulcers and postoperative wound dehiscences [91, 92]. Stein et al. [93]. in their *in vitro* study confirmed that low energy laser irradiation promotes proliferation and maturation of human osteoblasts, while stimulating effect of LLLT is explained by an increase of ATP in affected cells [94].

Photodynamic therapy (PDT) is being increasingly used in the management of MRONJ in combination with other therapeutic choices [90].

In the beginning photodynamic therapy (PDT) was used particularly to treat cancer and several studies have shown its antimicrobial potency [95–98]. Analyzing the effects of PDT on osteoblasts growth, study by Zancanela et al. [99] showed that PDT results in biostimulation of osteoblastic cell cultures or a cytotoxic effect depends of the applied dose. PDT has well documented clinical impact as adjuvant local treatment of ulcers and infected wounds, and potential indications for therapy of periodontitis and peri-implantitis, but treatment of MRONJ still in phase of collecting clinical results [100–105]. Treatment concept of MRONJ with PDT describes its use for symptomatic treatment in stage 0, preoperatively to reduce bacterial load and in cases with healing deficiencies, while in stages 1, 2 and 3 it is used after surgical treatment. Also it may be used as adjuvant conservative intervention for palliative therapy of compromised patients or in cases to avoid progression of disease when patients refuse surgery.

While application of LLLT for therapy of MRONJ has been described in numerous studies, there are few studies mainly focused on impact of photodynamic therapy of preventing occurrence of MRONJ. Vescovi et al. [89] used Nd:YAG laser biostimulation in addition to medical and surgical therapy and demonstrate a better healing tendency due to bony ablation, bactericidal and detoxification effect [106, 107]. Da Guarda et al. [108] reported a case of successful MRONJ treatment with the GaAIAs diode laser in combination with bone curettage. Summarizing the literature, use of LLLT is beneficial for treatment of MRONJ, although till today there are no large studies that proves significant improvement.

One of promoting factor in mechanism of MRONJ is presence of microflora. Species such as *Fusobacterium, Eikenella, Bacillus, Actinomyces, Staphylococcus,* and *Streptococcus* are predisposed to survive in oxygen depleted areas of necrotic bone that lack blood supply [109, 110]. Although the identification of microbial biofilms

**Figure 7.** *Application of chemical medium (photosensitizer)- toluidine blue.*

and *Actinomyces* species as the leading bacterial pathogen isolated from patients with MRONJ, there is unclear definitive treatment and no data reffering to bactericidal activity of laser therapy against *Actinomyces* species in MRONJ lesions.

The most used PDT system is one with mobile diode laser and dye (HELBO) with methylene blue (MB) (**Figure 8**). It has shown very promising results during surgical procedures or as adjuvant therapy in cases of postoperative wound dehiscences in patients with MRONJ. Photosensitizers's antimicrobial activity is mediated by singlet oxygen, which has high chemical reactivity and results with a direct effect on extracellular molecules. The polysaccharides present in extracellular matrix of a bacterial biofilm are sensitive to photodamage, so breaking biofilms can interrupt colonization and prevent antibiotic resistance [111].

Although is surgical treatment first option to deal with MRONJ, appliance of photodynamic therapy has several advantages. Before surgery usually we treat symptoms of MRONJ infection, such as swelling, purulent discharge and pain. They can be managed by bio-stimulative effect of the laser, especially those with advanced primary disease or those suffering from other sickness resulting in a general poor health [90]. PDT might be very sufficient in early stages of osteonecrosis promoting secondary granulation and formation of mucosal coverage, so surgery can be avoid. Unfortunately there are no controlled studies opposing PDT and LLLT to evaluate use of photosensitizer. Appliance of photodynamic therapy immediately after surgery could decrease complications of impaired healing of the wound (**Figure 9**).

In conclusion, although MRONJ is considered difficult to treat and may even be recalcitrant to therapy, photodynamic therapy can be a viable supportive tool

**Figure 8.**

*Antimicrobial photodynamic therapy using low-power diode laser (aPDT mode, LaserHF, HagernnnnnWerken).*

**Figure 9.** *MRONJ before and 2 months after treatment with combined therapy (surgery/aPDT/PRGF).*

of initial and advanced stages of MRONJ, as an adjuvant treatment before or after surgery or primary treatment in cases without surgery indicated.
