1. PREVENTION IS THE BEST STRATEGY, THE SAME AS FOR ANY OTHER ILLNESS (IF YOU RECOGNIZE IT, YOU AVOID IT)

2. PATIENTS BEING TREATED WITH BPS FOR LESS THAN FIVE YEARS NO CHANGE IN THE SURGICAL TREATMENT PLAN PATIENTS BEING TREATED WITH BPS FOR MORE THAN FIVE YEARS IT IS ADVISABLE TO SUSPEND BISPHOSPHONATE THERAPY THREE MONTHS BEFORE SURGERY AND RESUME THERAPY THREE MONTHS AFTER, POSSIBLY WITH A NON- AMINOBISPHOSPHONATE

3. ONJ : Stage 1 CLINICAL CONDITION Exposed bone AsymptomaticTREATMENT Rinsing with baking soda Put gel chlorexidine on onsteonecrotic area Check-ups every 15-20 days Teaching the patient oral hygiene Continue treatment with bps?

4. ONJ : Stage 2 CLINICAL CONDITION Exposed bone Infection TREATMENT Broad-spectrum antibiotics for 2-3 months Antimicotics for 15 days Rinsing with baking soda Put gel chlorexidine on osteonecrotic area Controlling pain with analgesics and anti- inflammatory drugs Very light, minimum bone curettage

5. ONJ : Stage 3 CLINICALCONDITION Exposed bone Infections, Fractures, Fistulae TREATMENT - Specifically placed antibiotics based on culture test - Rinsing with chlorexidine - Controlling the pain - Delicate bone curettage (carried out by experts in maxillofacial surgery) - prpl - frp - Tissue engineering - Low dose intermittent recombinant parathyroid hormone ( 1-34)

6. PATIENTS TAKING ORAL BISPHOSPHONATES HEAL MORE EASILY THAN PATIENTS ADMINISTERED BISPHONSPHONATES INTRAVENOUSLY (ONCOLOGIC PATIENTS)

7. SISBO (Italian society of study bisphosphonates in Odontostomatology) UPDATE Oncologic patients who take corticosteroids are those most at risk. It is to note that an increase of jaw osteonecrosis has been reported in patients treated with antineoplastic drugs who have never taken bisphosphonates nor undergone radiotherapy. Diabetic patients and those who have an arteriovenous insufficiency should be kept under observation. Thrombophylia, hypofibrinolysis, and hypercholesterolemia are considered important instigating factors. We advise (only for very high risk patients: oncologic patients who have been taking high doses of bps for several years and who are more than seventy years old) to carry out: serum CTX, urinary NTX (which must be evaluated by expert colleagues), a blood clotting check-up, (PT, INR, PTT), platelet count, vitamin K dosage, calcemia, vitamin D dosage (1,25)D and PTH. Measuring the vitamin D dosage is very important because a deficiency is the cause of secondary osteoporosis, secondary hyperparathyroidism, and also of disreactive immune response. Chronic alteration of the calcium balance damages the formation of new bone.

8. TREATMENT PLAN For all patients taking bisphosphonates orally or intramuscularly (except oncologic patients) without ONJ 1.Antibiotic therapy starting 5 days before the oral surgery until 8-10 days after; 2. Taking vitamins E and D 3.Always carry out surgical sutures when possible 4. Advise mouthwashing with bicarbonate of soda 5. Teach the patient to apply chlorexidine gel and vitamin E gel on the surgical wounds. 6. Substitute the amino-bisphosphonate therapy with a non-aminobisphosphonate (chlodronate) one. 7. Check-ups every 15 days for the first two months. 8. The patients must abstain from smoking or drinking alcohol. 9) Intermittent doses of PTH ricombinate (1-34)( Forteo ) 10) Pentoxiphylline

9. For all patients taking bisphosphonates with ONJ 1. Antibiotic and antimicotic therapy 2. Warm mouthwashes with bicarbonate of soda : neutralise the Ph acid, the accumulation of phosphorous in the jaw bones and inhibit the release of the bisphosphonates 3. Mouthwashes with warm physiologic solution 4. High doses of vitamin E (tocopherol)1000 UI daily for 2-3 months 5. Pentoxiphylline (improves the calcium pump, is vasoactive and defibrinogenating) 6. Chlodronate( Volpi et al.), (Takefumi et al) 7.Low doses of low-molecular-wieght Enoxaparin (anticoagulant) 8. Vitamin D and Vitamin K 9. Intermittent doses of PTH (1-34) ( don’t use in patient with metastasis) 10.ACTH ?? 11. Hyperbaric oxygen 12. Ozone therapy 13. Electrical stimulation 14. Intermittent low frequency laser 15. Magneteterapy TREATMENT PLAN

10. THE FUTURE OF BISPHOSPHONATES: 1.IMPERFECT OSTEOGENESIS 2.PAGET’S BONE DISEASE 3.PERIPROSTHESIS BMD LOSS 4.PERIMPLANT BONE LOSS 5.DELAYED BONE UNION ( BONE GRAFTS) 6.OSTEONECROSI S OF THE FEMORAL HEAD 7.PERIODONTAL DISEASES 8.ORAL IMPLANTS 9.BIOMATERIALS FOR BONE RIGENERATION 10.AUTOIMMUNE DISEASES 11.ANTIBIOTIC RESISTANCE

11. ALWAYS REMEMBER: PREVENTION IS IMPERATIVE! -CASE HISTORY (FUNDAMENTAL) -FEAR (NO) -PANIC (NO) -CARE (YES)

12. the company is available to all colleagues : Presidente sisbo: raff.volpi@tiscali.itraff.volpi@tiscali.it Referente sisbo: info@sisbo.it