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I overview 22 I implants2_2013 Fig. 5_First reports on bisphosphonate-related osteonecrosis of the jaw. Fig. 6_Therapy recommendations for BRONJ depending on the stage of the disease (AAOMS, Ruggiero et al. 2009). bone surface in the resorption lacunae under the os- teoclasts.Theyareresorbedbyosteoclastsandresultin cell inactivation and a loss of their ruffled border. Due tothelossoftheirruffledborder,thecellsurfaceofthe osteoblasts diminishes and they thus lose their ability to resorb bone. In addition, an increased apoptosis of osteoclasts occurs at higher doses. Besides the inhibi- tionofosteoclasts,osteoblastsareinhibitedaswell. Thetherapeuticeffectofbisphosphonatesconsists in the fact that the inhibition of osteoclasts exceeds the inhibition of osteoblasts. This results in a positive balanceinboneremodellinginfavourofboneforma- tion and in a reduction of the bone remodelling rate. Themostcommonclinicalindicationforbisphospho- natesisthetreatmentofosteoporosis.Theyarehighly effective in this field. They effect an increase in bone density and a reduction in bone loss both in post- menopausalandinsteroid-inducedosteoporosis.The field of application of bisphosphonates for malignant diseasesincludesosteolyticbonemetastasesandmul- tiplemyeloma.Thebisphosphonatescontributetore- duce the risk of skeleton-related events in patients. Theyhavepositiveeffectsonaseriesofcomplications such as acute hypercalcaemia, new bone metastases, diffuse bone pain and protect against pathological fractures. Osteoporosis treatment is usually carried out using tablets. Intravenous administration of bis- phosphonates is common in particular in oncology. The dosing for the treatment of osteoporosis is many timeslowerthanforthetreatmentinoncology. The activity of a bisphosphonate is defined by the amount of substance that is necessary in order to ef- fectivelyinhibitboneresorption.Thehighertheactiv- ity, the greater is the potency of the bisphosphonate. The relative potency of bisphosphonates is related to the potency of the non-amino bisphosphonate etidronate. Etidronate is the oldest bisphosphonate available for clinical use. Table 1 shows a selection of therapeutically proven bisphosphonates. Only 1–10 per cent of orally administered bisphosphonates are resorbed.Theybindtoalbumininthebloodandhavea veryhighaffinitytohydroxylicapatiteofthebone.The half-life period in bone ranges from years to decades. Accumulation occurs in case of repeated application. Elimination takes place via the renal route. Bisphos- phonates have side effects. The most important side effectsare:gastrointestinalproblems,acutephasere- action,renallesionsandosteonecrosisofthejaw. _Bisphosphonate-related osteonecrosis of the jaw (BRONJ) Bisphosphonate-related osteonecrosis of the jaw was described for the first time in 2003. Early reports are listed in Figure 5. More than 400 case series were publishedintheyearsthatfollowed.Thegreatincrease inthenumberofcasereportsmightalsobebecauseof theincreaseduseofbisphosphonatesinthetreatment ofosteoporosisandtumours.Withrespecttothedef- initionofosteonecrosisofthejawundertherapywith bisphosphonates, there is no agreement in literature regarding nomenclature and inclusion criteria. The suggestion of the American Association of Oral and Maxillofacial Surgeons (AAOMS) is quoted most fre- quently. According to that, the disease is called bis- phosphonate-related osteonecrosis of the jaw (BRONJ).ThecriteriaforthepresenceofBRONJare: –currentorearliertreatmentwithbisphosphonate –uncovered, necrotic bone in the jaw for more than eightweeks –nohistoryofradiotherapyinthegnathofacialregion. Uptonow,thereisnosatisfactorypathogeneticex- planation for which mechanisms are responsible for causing osteonecrosis due to bisphosphonates in the end. Only hypotheses serve as approaches to explain Stage 0 • unspecific symptoms • no bone necrosis • symptomatic pain therapy • if necessary,antibiotic therapy antibacterialmouthwashsolution(CHX0.2%) Antibiotictherapy Paintherapy Surgicaldebridement • frequent recalls • patient instruction Stage 1 • exposed necrotic bone • asymptomatic patients • no evidence of infection Stage 2 • exposed necrotic bone • symptomatic patients • clinical evidence of infection Stage 3 • exposed necrotic bone • symptomatic patients with pain and evidence of infection • evidence at least one of the following complications 1.pathological fracture 2.extraoral fistula 3.oral-antral communication 4.extended osteolyses – 2003: Marx (36 cases),Migliorati (5 cases), Carter et al.(3 cases),Wang et al. (3 cases) – 2004: Ruggiero et al.(63 cases) Communication of the Ärztekommission [Medical Committee] Dtsch.Ärzteblatt (Aug.2004) Hoefert et Eufinger (3 cases) Information given by Novartis company (3 cases) – 2005: Marx (119 cases)