**6. Prophylaxis and treatment of BONJ**

Recently inIn recent literature is found date for, a new type of complication associated with bisphosphonate intake –has been found, which is called avascular necrosis of the jaws. It is defined as necrosis associated with or without dental procedures, which could persist for more than 6-8 weeks with irresponsive to conservative treatment, found in patients without history of previous radiotherapy in the area affected but treated with nitrogen group bisphosphonates with nitrogen group, i.v. through IV for at least a year or per os for longer period, and associated with general condition withof bone resorption. Similar cases arewere published for the first time in 2003 by Marx with patients treated with pamidronate and zoledronate. Later, Carter and Gross, Ruggierro, Migliorati, and Wang reportalso reported similar cases. In 2005, Novartis (Aredia and Zometa48 producer) officially declaredeclared 475 cases of Bisphosph‐ onate bisphosphonate-related osteonecrosis of the jaws. In nowadaysNowadays, the number of affected patients worldwide is unknown. Scientific literatures says the BONJ is from 1,.3% to 10%. More There are more than 5,.1 million patients are treated with bisphosphonates. More and more than 2 million acceptaccepted BPs as antimalignatanti-malignant therapy. The number of patients treated for osteoporosis with BPs is increasing rapidly. More than 10 million patients, mainly women in the USA has, have osteoporosis,. It and it is supposed that the number will increase to 12 million and 34. Thirty-four million patients older than 50 have decreased bone density and considered high risk for osteoporosis development. Oral BPs arewere prescribed to more than 70% of the patients diagnosed with osteoporosis in US during the USA in 2003- to 2006.((American association of Oral and Maxillofacial Surgeons)). More than 190 million prescriptions arewere issued in North America. In 2003 Alendronate, alendronate is 19th most prescribed medicine (17 million prescriptions) Risedronate), risedro‐ nate is 72nd (6 million prescriptions) zolendronate), while zoledronate is used from more than

Bisphosphonate-associated osteonecrosis of the jaws is a result of treatment with BPs, bone metabolism disorders and physiological micro damagemicrodamage of the jaws interferin‐ ginterfere their biomechanical properties. Oral cavity conditions, microtrauma, infections increase the efforts of the organism to bone recovery, exceeding the ability of the hipodynamic bone. Compared to all other bones maxilla and mandible are remodeled most frequently in the human body. This is the reason why BONJ is observed only in jaw-bones. Unlike to other bones in the human body, they are not enough protected enough. It is an important fact that only a thin mucosa and a periosteum are the only barriers protecting bone from injuries. From the other side teeth are prerequisite to easy microorganisms penetration and development of internal infections–caries and periodontal disease complications. It is interesting to mention that local factors like partial and full removable dentures are also factors that increase the risk

of osteonecrosis. Smoking and continuous corticosteroid therapy are also risk factors.

According to Denn et al., all osteonecrosis cases describe todescribed in 2006 arewere associ‐ ated with nitrogen containing bisphosphonates. In scientific literature, there is no single opinion which bisphosphonates exactly leads to more frequent BONJ development. The

300,000 sick people.

**5. Pathophisiology of BONJ**

132 Immunopathology and Immunomodulation

In literature, there is no solidarity concerning bisphosphonate therapy suspension after the appearance of jaw-osteonecrosis. Marx suggests bisphosphonate therapy in onco-patients to be discussed with an oncologist in order to define positive effect/risk ratio, having in mind bisphosphonatebisphosphonate's half-life (10 years).

In literature thereThere is prevalence of BONJ with prior dental procedures compared to the so called spontaneous osteonecrosis and 33%–86% of the BONJ in literature are described after different dental procedures.

Prevailing opinion is that with ageas one gets older the danger from bisphosphonate osteo‐ necrosis increases withby 9%.

Behavior inof diagnosed osteonecrosis patients is dependent on the disease stage. It should be mentioned that American Association of Oral and Maxillofacial Surgeons proposeproposed a change in the disease nomenclature formfrom BONJ to Medicine medication-related osteo‐ necrosis of the jaws (MRONJ). The reason is an increasing number of patients with osteonec‐ rosis of the jaws have been diagnosed after other drug intake (denosumab). Due to this reason Hence, the AAOMS changeschanged the name, which was accepted in 2009, on. On their consensus conference in 2014, with a Position Paper and in addition to the new name accepts, they accepted new diagnostic and treatment strategies corresponding to the contemporary researches., as follows:


According to AAOMSAAOMS's Position Paper, it is possible to think about MRONJ if several characteristics are present:


It should be mentioned that, according to the AAOMS, risk for osteonecrosis development in patients with bone tumors treated with zoledronate is 0% to 1%. It is similar in patients treated with denozumab.denosumab. A bit lower is the valuepercentage risk in patients treated with antiangiognetic drugs, like bevacizumab –, which is 0.2%. The risk for patients with osteopo‐ rosis treated with denozumabdenosumab and zoledoronate is 0.04%. It should be noted that with increasingthe longer the period of time for treatment is increasingthe higher the risk for jaw osteonecrosis form, from 0.5% for one year of treatment to 1.1% for three year years of treatment. After all it is a matter ofThese are based on retrospective studies of treated patients, which who have not been treated surgically in the oral cavity but has develophave developed spontaneous osteonecrosis. As aA trigger factor could be underlined tooth or even multiple teeth extraction and placement of dental implants. In differentDifferent retrospective studies are shown showed that 1.6% to 14.8% of patients treated i.v.through IV with BPs for longer than a year period of time and have developed osteonecrosis developed after tooth extraction. According to a research done by Carlos Pigrau – –Serralach et al since 2014, BONJ reachescases have reached 30.2% Viridance since 2014. Viridans group Streptococcistreptococci are isolated in 83.3% formfrom the cases and AcctinomycesActinomyces spp in 39.0% from all bone histological samples.

According to other studies, between 52% and 61% from all cases described of osteonecrosis of patientscases treated with bisphosphonates are triggered after surgical treatment – –a per‐ centage that is extremely high. Retrospective research done by Kunchur R,., Need A,., Hughes T,., et al. in 2009, says stated that from0.5% out of 194 patients treated with oral bisphospho‐ nates have developed osteonecrosis occurrence is 0.5% after tooth extraction. They assumeas‐ sumed that dental implant placement iswas with similar biological load as tooth extraction. Moreover, Donggeol Lee reportsreported that 77 patients treated with bisphosphonate undergounderwent implantology treatment, with 78 placed implants with 97.4% success equal to success in normal conditions. Sebastien Hoefert and Harald Eufinger report i.v.reported IV and per os antibiotic treatment in bisphosphonate treated patients before surgical treatment.

In 2009, P. Pechalova, A. Bakardjiev, B. Vladimirov, E. Poryazova, I. Angelova, and A. Jeleva publishpublished a case of a patient with bisphosphonate osteonecrosis of the mandible of a patient after consistent oral intake of 14 month consistent intake for fourteen months of FosamaxR (alendronate) (70mg per week dosage, taken once a week) and BonvivaR (ibadro‐ nate) (150mg month dosage, taken once a month) on the occasion ofdue to severe osteoporosis with pathological fractures of vertebras. The oddly think in the case published is bone sequester covered entirely with mucosa. Without fistula..

A group formfrom ITI (Bornstein, Cionca, Momblli)), based on a vast literature in 2009 differentiate, differentiated the surgeon behavior in patients with oral and i.v.IV bisphospho‐ nate intake. They assumeassumed that, in addition to the way of intake there is, the duration of intake played an important role of the duration.. They saysaid that patients with osteopo‐ rosis/osteopenia take much lower dosage of bisphosphonate compared to cancer patients and, thus, the accumulation of the medicine should be several years. This is enough to conclude that In conclusion, patients who underwent oral surgical procedures are withhave significantly lower risk of necrosis in these patientscompared to those who had IV bisphosphonate intake.

Similar conclusions are were made by our team on the basis of 3 treatedthree patients in 3 yearswho underwent treatment for the period of three years. One of the patients were onhad an oral intake of bisphosphonates, one i.v.had IV, and one on DenozumabeDenosumabe (subcutaneоus) As part of our). Our entire biological concept treatment include includes preliminary antibiotic treatment, irrigation with chlorxeidine solutions, general and local ozone therapy, hyperbaric chamber, PRGF usage, Er;Yag:YAG laser, photodynamic therapy, and minimally invasive surgical techniques.

### **7. Conclusions**

**1.** I.v.IV bisphosphonates for treatment of primary bone tumors and bone metastasis,

**2.** Oral bisphosphonates mainly for osteoporosis and osteopenia treatment, as well as

**3.** DenozumabDenosumab–RANK ligand inhibitor–it inhibits bone resorption by inhibition of the function of osteoclasts and as an advantage could be mentioned that it is not connected to the bone so within 6 months after treatment the risk of complications is

**4.** Antiangiogenetic medications–it is used in different tumor conditions and is useful due to the fact that preventsto prevent formation of new blood vessels. It connects to signal molecules responsible for blood vessels formation and interfereinterferes the angiogenesis

According to AAOMSAAOMS's Position Paper, it is possible to think about MRONJ if several

**1.** Antiresorptive or atiangiogenicantiangiogenic treatment conducted before or in the past.,

**2.** Bone that is exposed in the maxillofacial region through intraoral or extraoral fistula(e)

It should be mentioned that, according to the AAOMS, risk for osteonecrosis development in patients with bone tumors treated with zoledronate is 0% to 1%. It is similar in patients treated with denozumab.denosumab. A bit lower is the valuepercentage risk in patients treated with antiangiognetic drugs, like bevacizumab –, which is 0.2%. The risk for patients with osteopo‐ rosis treated with denozumabdenosumab and zoledoronate is 0.04%. It should be noted that with increasingthe longer the period of time for treatment is increasingthe higher the risk for jaw osteonecrosis form, from 0.5% for one year of treatment to 1.1% for three year years of treatment. After all it is a matter ofThese are based on retrospective studies of treated patients, which who have not been treated surgically in the oral cavity but has develophave developed spontaneous osteonecrosis. As aA trigger factor could be underlined tooth or even multiple teeth extraction and placement of dental implants. In differentDifferent retrospective studies are shown showed that 1.6% to 14.8% of patients treated i.v.through IV with BPs for longer than a year period of time and have developed osteonecrosis developed after tooth extraction. According to a research done by Carlos Pigrau – –Serralach et al since 2014, BONJ reachescases have reached 30.2% Viridance since 2014. Viridans group Streptococcistreptococci are isolated in 83.3% formfrom the cases and AcctinomycesActinomyces spp in 39.0% from all bone

According to other studies, between 52% and 61% from all cases described of osteonecrosis of patientscases treated with bisphosphonates are triggered after surgical treatment – –a per‐ centage that is extremely high. Retrospective research done by Kunchur R,., Need A,., Hughes T,., et al. in 2009, says stated that from0.5% out of 194 patients treated with oral bisphospho‐

**3.** Lack of radiation therapy in the oro-facial region or metastatic disease to the jaws.

multiple myeloma, and severe osteoporosis but with lower dosage.

PagetPaget's disease and osteogenesis imperfectimperfecta.

slightly noticeable.

134 Immunopathology and Immunomodulation

signaling cascade.

characteristics are present:

histological samples.

persisting for more than 8 weeks, and

During an surgical, respectively a surgery, such as implantology treatment, especially in bisphosphonate treated patients it is vital antibiotics preparation and is vital for the primary healing process to be guaranteed, especially in bisphosphonate treated patients. Usage of Clindamycin as osteotopicosteotropic antibiotics is a gold standard assuring lackto ensure absence of post-operation infection and prevention of complications. LackThe absence of dehiscence assureensures us smooth osteointegration process and lack of bone lose. That is whyFor this purpose, the common requirements for soft tissue management, include suitable implantology system, proper operation technique, atraumatic preparation, and last but not least proper suturing materials and technique. Implantology has extra sources like PRP, PRF,, PRGF, which could be applied with great success if it's needed. The high concentration of platelets rich in growth factors (PRGF) in the operation field contributecontributes to a light and with lack of troublestrouble-free post-operative process, guaranteeing perfect conditions for the osteointegration process. In cases of post-operative complications MethronidazoleMe‐ tronidazole is a matter of choice.

#### **8. Clinical cases**

#### **8.1. Case 1**

The patient has arrived at our clinic for the first time in 2009 with pain syndrome, periodontal abscess in the 47, 44, 31, 32, 41, and 42 area due to periodontitis developed formfrom the plaque with periodontal pockets form 6from 6mm to 8mm.,combined with chronic occlusal trauma from iatrogenic sharp edges of metal-ceramic constructions made years ago (X-ray, Fig. 1). Based on the anamnesis, a treatment with medicines was found–6 months treatment with Bonviva medicine–3mg once a month parenteral, associated with diagnosed osteopenia in 2007 with quantitative osteometry over tibia bone with T-score 2,9. It was considered that due to the short-term treatment with the bisphosphonate medicine and the 5five-year period after it by keepingto keep certain protocol for preparation and implantation, an implantology treatment could be initiated. A multiple extraction of 47, 44, 42, 41, 31, and 32 was undertaken after antibiotic protection, initial ultrasonic and sand-blasting therapy divided in tointo several appointments, high-intensity and low intensity laser therapy, local and general ozone therapy and hyperbaric therapy. Extraction sockets were filled with PRGF and sutured with PTFE. As an additional prophylaxis measure from bisphosphonates induced osteonecrosis, photody‐ namic therapy was used. The healing process was without any complications.

The treatment plane includesplan included the entire sanitation of the mouth, periodontal and endodontic preparation, and placement of 11 pieces titanium screwed implants. After uncov‐ ering of the implants, tooth 43 was planplanned for extraction despite the exact root-canal treatment, due theto long term prognosis and high risk of root fracture. TillUntil that time, this particular tooth was used for temporary fixed construction abutment. Because of the short clinical crowns, crown-lengthening was planplanned and performed with Er:YAG laser, based on the preliminary analysis of the size and shape of future prosthetic crowns and attached gingiva available. X-ray surgical guide was made, along with a prototype of the future prosthetic constructions, and was used for the CT. Due to the fact of previous bisphosphonate usage, a certain surgical protocol was used again including: antibiotic prophylaxis, highintensity and low intensity laser therapy, local and general ozone therapy, hyperbaric therapy, PRGF, precise soft-tissue management and photodynamic therapy. One implant was placed in 15 area. Due to the lack of complications it was proceeded to, the placement of the rest of the planned implants proceeded. Bone type was D4 for the maxilla and D3 for the mandible. Bone spreaders were used for bone condensation. The primary stability of the implants was 15 up to 30 N/cm. Osteotomic implant beds were shaped by the usage of the existing surgical guide. Existing bone doesdid not demandeddemand additional augmentative procedures. Suture material was 4/0 PTFE. On the both jaws, fixed long-term temporary constructions waswere provided. After longer than usual period of waiting (more than ana year)), implants were uncovered by half-thickness flaps moved apically. All 11 implants were osteointegrated. After open-tray, impression technique with transfers zirconium abutments with titanium base were made. CAD-CAM zirconium constructions were madmade directly on the same model. In the frontal area constructions were made by blend-ceramic and distally full anatomy zirconium.

Complete functional rehabilitation of the masticatory apparatus was achieved. Aesthetic demands of the patient was covered completely.

**Figure 6.** Basic X-ray

platelets rich in growth factors (PRGF) in the operation field contributecontributes to a light and with lack of troublestrouble-free post-operative process, guaranteeing perfect conditions for the osteointegration process. In cases of post-operative complications MethronidazoleMe‐

The patient has arrived at our clinic for the first time in 2009 with pain syndrome, periodontal abscess in the 47, 44, 31, 32, 41, and 42 area due to periodontitis developed formfrom the plaque with periodontal pockets form 6from 6mm to 8mm.,combined with chronic occlusal trauma from iatrogenic sharp edges of metal-ceramic constructions made years ago (X-ray, Fig. 1). Based on the anamnesis, a treatment with medicines was found–6 months treatment with Bonviva medicine–3mg once a month parenteral, associated with diagnosed osteopenia in 2007 with quantitative osteometry over tibia bone with T-score 2,9. It was considered that due to the short-term treatment with the bisphosphonate medicine and the 5five-year period after it by keepingto keep certain protocol for preparation and implantation, an implantology treatment could be initiated. A multiple extraction of 47, 44, 42, 41, 31, and 32 was undertaken after antibiotic protection, initial ultrasonic and sand-blasting therapy divided in tointo several appointments, high-intensity and low intensity laser therapy, local and general ozone therapy and hyperbaric therapy. Extraction sockets were filled with PRGF and sutured with PTFE. As an additional prophylaxis measure from bisphosphonates induced osteonecrosis, photody‐

namic therapy was used. The healing process was without any complications.

The treatment plane includesplan included the entire sanitation of the mouth, periodontal and endodontic preparation, and placement of 11 pieces titanium screwed implants. After uncov‐ ering of the implants, tooth 43 was planplanned for extraction despite the exact root-canal treatment, due theto long term prognosis and high risk of root fracture. TillUntil that time, this particular tooth was used for temporary fixed construction abutment. Because of the short clinical crowns, crown-lengthening was planplanned and performed with Er:YAG laser, based on the preliminary analysis of the size and shape of future prosthetic crowns and attached gingiva available. X-ray surgical guide was made, along with a prototype of the future prosthetic constructions, and was used for the CT. Due to the fact of previous bisphosphonate usage, a certain surgical protocol was used again including: antibiotic prophylaxis, highintensity and low intensity laser therapy, local and general ozone therapy, hyperbaric therapy, PRGF, precise soft-tissue management and photodynamic therapy. One implant was placed in 15 area. Due to the lack of complications it was proceeded to, the placement of the rest of the planned implants proceeded. Bone type was D4 for the maxilla and D3 for the mandible. Bone spreaders were used for bone condensation. The primary stability of the implants was 15 up to 30 N/cm. Osteotomic implant beds were shaped by the usage of the existing surgical guide. Existing bone doesdid not demandeddemand additional augmentative procedures. Suture material was 4/0 PTFE. On the both jaws, fixed long-term temporary constructions

tronidazole is a matter of choice.

136 Immunopathology and Immunomodulation

**8. Clinical cases**

**8.1. Case 1**

**Figure 7.** Intraoral situation after preliminary treatment

**Figure 8.** X-ray- before implant insertion

**Figure 9.** Minimal invasive insertion of the first implant

After preliminary treatment, the patient receivereceived one implnantimplant in the area of the second upper right premolar (15) accompanied with clindamycin prophylaxis, PRGF activation of the implant surface and covered by PRFG fibrin membrane, combined with postimplantationpost implantation photodynamic therapy using PhotoSan® for 4 minutes, two timetimes a day tilluntil the suture removal, and ozone therapy in the first three days combined with hyperbaric-chambers.

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**Figure 10.** Implant insertion in second quadrant

**Figure 8.** X-ray- before implant insertion

138 Immunopathology and Immunomodulation

**Figure 9.** Minimal invasive insertion of the first implant

combined with hyperbaric-chambers.

After preliminary treatment, the patient receivereceived one implnantimplant in the area of the second upper right premolar (15) accompanied with clindamycin prophylaxis, PRGF activation of the implant surface and covered by PRFG fibrin membrane, combined with postimplantationpost implantation photodynamic therapy using PhotoSan® for 4 minutes, two timetimes a day tilluntil the suture removal, and ozone therapy in the first three days

**Figure 11.** Implant insertion in lower jowjaw

**Figure 12.** Activation of implant surface with PRGF

**Figure 13.** PRGF membrane for covering of the implants

The high concentration of platelets rich in growth factors (PRGF) in the operation field contributecontributes to a light and with lack of troubles trouble-free post-operative process, guaranteeing perfect conditions for the osteointegration process.

The process of tissue repair iswas based on a complex cascade of biological events controlled by a long list of biologically active growth factors and proteins. The spatial and temporal action of this family of mediators on the tissue-damaged area regulates the mechanisms and phases that govern tissue repair and regeneration

**Figure 14.** Pure ozone injected subcutaneously in the manipulation area

The high concentration of platelets rich in growth factors (PRGF) in the operation field contributecontributes to a light and with lack of troubles trouble-free post-operative process,

The process of tissue repair iswas based on a complex cascade of biological events controlled by a long list of biologically active growth factors and proteins. The spatial and temporal action of this family of mediators on the tissue-damaged area regulates the mechanisms and phases

guaranteeing perfect conditions for the osteointegration process.

that govern tissue repair and regeneration

**Figure 13.** PRGF membrane for covering of the implants

**Figure 12.** Activation of implant surface with PRGF

140 Immunopathology and Immunomodulation

Another method used in our biological concept is ozone therapy. There are several known actions of ozone onin the human body, such as anti-microbial, immunostimulating, antihi‐ poxyc, analgesic, detoxicating, bioenergetics and biosynthetic (activation of the metabolism of carbohydrates, proteins and lipids)), etc. Ozone is a relatively rare and unstable molecule composed of three oxygen atoms O3. The normal oxygen molecule has two oxygen atoms O2. Stratospheric ozone is important in the earth system because it absorbs ultraviolet radiation from the sun, protecting life on earth. The beneficial biological effects of ozone, is its antimicrobialantimicrobial activity. How we can derive ozon?the ozone? Using a simple electric arc, we can produce ozone. In case, for example, of bone regeneration, for example, the purpose of ozone using ozone is the initial local growth factor expression and stimulatetion stimulate the migration of osteoprogenitor cells to the wound site and subsequentlyand subsequently, in a controlled fashion, to direct their differentiation to the osteogenic cell line. Throughout this process, another set of factors will regulate the dynamic equilibrium between cell inhibi‐ tion and proliferation, as well as angiogenesis and extracellular matrix formation. Ozonegenerator can introduce pure ozone in saline. Ozone infusion is also precious for the fact that it generates a therapeutic effect on faster post op wound healing and preliminary preparation of the patient by avoiding further complications and assuring on 99% smooth primary closure. Anti-microbial effect of ozone asis a result of its action on cells by damaging its cytoplasmatic membrane due to ozonolysis of dual bonds and also ozone-induced modification of intercel‐ lular contents because of secondary oxidants effects. This action is non-specific and selective to microbial cells, it does not dameagedamage human cells because of their major antioxidative ability. Ozone is very efficient in antibiotics resistant strains. Its anti-microbial activity increases in liquid environment of acidic pH. In viral infections, the ozone action lies in the intolerance of infected cells to peroxides and change of activity of reverse transcriptase, which takes part in synthesis of viral proteins.

**Figure 15.** Usage of photodynamic therapy contributecontributes to cell destruction of the microorganisms and pre‐ ventprevents complications and accelerateaccelerates wound healing

**Figure 16.** Photodynamic therapy with photodynamic intraoral tray

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**Figure 17.** Minimal invasive extraction of 43- root separation

intolerance of infected cells to peroxides and change of activity of reverse transcriptase, which

**Figure 15.** Usage of photodynamic therapy contributecontributes to cell destruction of the microorganisms and pre‐

ventprevents complications and accelerateaccelerates wound healing

**Figure 16.** Photodynamic therapy with photodynamic intraoral tray

takes part in synthesis of viral proteins.

142 Immunopathology and Immunomodulation

**Figure 18.** Minimal invasive extraction of 43

**Figure 19.** Granulation tissue ablation with Er:YagYAG laser

**Figure 20.** Palatal connective tissue graft

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**Figure 21.** Palatal connective tissue graft in PRGF

**Figure 19.** Granulation tissue ablation with Er:YagYAG laser

144 Immunopathology and Immunomodulation

**Figure 20.** Palatal connective tissue graft

**Figure 22.** Bone graft material mixed with PRGF

**Figure 23.** Bone graft material mixed with PRGF in postextractionpost-extraction socket

**Figure 24.** PRGF-clot cloth

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**Figure 25.** Covering of bone graft material with the PRGF clotcloth

**Figure 23.** Bone graft material mixed with PRGF in postextractionpost-extraction socket

**Figure 24.** PRGF-clot cloth

146 Immunopathology and Immunomodulation

**Figure 26.** Suturing of the palatal connective tissue graft over the postextracted socetpost-extracted socket

**Figure 27.** Soft healing process

**Figure 28.** The end result

**Figure 29.** End result after treatment

#### **8.2. Case 2**

**Figure 27.** Soft healing process

148 Immunopathology and Immunomodulation

**Figure 28.** The end result

**Figure 29.** End result after treatment

A female patient, 57 years old, S. H. in good general good health, non-smoker, was received at the clinic with complainscomplaints of mobility of the entire upper jaw prosthetic fixed construction, accompanied with pain and inability to eat, dating back to 3 months earlier. Clinical exam findfound out significant mobility (4th degree by Miller) of metal-ceramic fixed one-piece bridge prosthetic construction of the upper jaw. (Fig. 2). On the X-ray (Fig.1), 4 screwing dental implants arewere observed, "Tramonte design" and 4four residual roots were in terminal stage. There iswas a significant bone resorption around the implants visible on the x-ray (proven lack of osteointegration.). From the patient histori ispatient's history, it was known that these implants arewere placed 5five years ago. AnA year later, patient beginsbegan treatment with Fozamax per os once a week withfor the duration 2of two years because of osteoporosis diagnosediagnosis (T-scorscore-2.9%).

**Figure 30.** Initial X-ray

**Figure 31.** Intraoral view

After initial periodontal therapy, with ultrasonic device and highintensityhigh intensity laser, under antibiotic cover (clindamycin 600mg. /./8h per os), 2two times hyperbaric chamber before and three times after the dental procedures, saline enriched with ozone 9nine times and three were locally applied subcutaneously, photodynamic therapy tilluntil the 10th den after the dental procedure of removing all residual roots and implants. In the extraction sockets were placed PRGF cloth, collagen sponge and the wound were sutured. Post-operative period was smooth without any pain or complications. The patientspatient was given an immediate fabricated total removable dentures.

**Figure 32.** Intraoral view after bridge removal

**Figure 33.** All implants, teeth and bridge after removal

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**Figure 34.** Granulation tissue ablation with Er:YagYAG laser

before and three times after the dental procedures, saline enriched with ozone 9nine times and three were locally applied subcutaneously, photodynamic therapy tilluntil the 10th den after the dental procedure of removing all residual roots and implants. In the extraction sockets were placed PRGF cloth, collagen sponge and the wound were sutured. Post-operative period was smooth without any pain or complications. The patientspatient was given an immediate

fabricated total removable dentures.

150 Immunopathology and Immunomodulation

**Figure 32.** Intraoral view after bridge removal

**Figure 33.** All implants, teeth and bridge after removal

**Figure 35.** PRGF – cloth

**Figure 36.** Covering with collagen sponge and suturing

**Figure 37.** Day after surgery

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**Figure 38.** Ten days after surgery

**Figure 36.** Covering with collagen sponge and suturing

152 Immunopathology and Immunomodulation

**Figure 37.** Day after surgery

**Figure 39.** Three weeks after surgery

**Figure 40.** Intraoral view after implant insertion

**Figure 41.** Intraoral view after suturing

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**Figure 42.** Two weeks after surgery

**Figure 40.** Intraoral view after implant insertion

154 Immunopathology and Immunomodulation

**Figure 41.** Intraoral view after suturing

**Figure 43.** Panoramic X-ray after surgery

**Figure 44.** Four weeks after surgery

#### **8.3. Case 3**

A female patient, 54 years old, in good general health condition, smoker (over 10 cigarettes per day), was received at the clinic with complainscomplaints from fixed prosthetic construc‐ tion mobility on the upper jaw, poor aesthetics, and inability to eat normally. X-ray proves anand aggressive periodntoalperiodontal disease with more than 9-10mm910mm bone resorption of interdental bone. PatientPatient's history sayssaid that she is was on Denosu‐ mabdenosumab (subcutaneously every 6 months) during for the last 3three years –in treatment for osteoporosis diagnose. The treatment plan was similar with case N2 and the healing process went smoothsmoothly.

**Figure 45.** Intraoral view

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**Figure 46.** Postextracted sockets

**Figure 44.** Four weeks after surgery

156 Immunopathology and Immunomodulation

went smoothsmoothly.

**Figure 45.** Intraoral view

A female patient, 54 years old, in good general health condition, smoker (over 10 cigarettes per day), was received at the clinic with complainscomplaints from fixed prosthetic construc‐ tion mobility on the upper jaw, poor aesthetics, and inability to eat normally. X-ray proves anand aggressive periodntoalperiodontal disease with more than 9-10mm910mm bone resorption of interdental bone. PatientPatient's history sayssaid that she is was on Denosu‐ mabdenosumab (subcutaneously every 6 months) during for the last 3three years –in treatment for osteoporosis diagnose. The treatment plan was similar with case N2 and the healing process

**8.3. Case 3**

**Figure 47.** The extracted teeth

**Figure 48.** Granulation tissue ablation with Er:YagYAG laser

#### **Figure 49.** PRGF clotcloth

**Figure 50.** Covering with collagen sponge and suturing

**Figure 51.** The immediate denture

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#### **Figure 52.** Three weeks after extraction

**Figure 49.** PRGF clotcloth

158 Immunopathology and Immunomodulation

**Figure 50.** Covering with collagen sponge and suturing

**Figure 51.** The immediate denture

\*All case-pictures are Dr. Abadzhiev's private practice patiens.


**Table 1.** Usage and dosage of the bisphosphonates

After R.E. Marx


**Table 2.** Staging and Treatment Strategies

Position Paper of American Association of Oral and Maxillofacial Surgeons (2014)

#### **Author details**

Metodi Abadzhiev\*

Address all correspondence to: abaimplant@abv.bg

MU-Varna, Faculty of Dental Medicine, Bulgaria
