Dr Alison DougallConsultant for Medically Compromised Patients

Dublin Dental School and Hospital

Bis-phosphonates update

• Fear• Confusion• Uncertainty• Risk• Panic• Warning• Litigation

PATIENT WARNING : avoid invasive dentistry!!!

Jump into unknown = TroubleFear = Neglect

How much do we need to know?

1st Generation – oral bisphosphonates

• Introduced in 1990’s• Improve bone quality in

Pagets Disease• Osteoporosis

– Alternative to HRT in post menopause women

– Prevent fractures of spine, wrist and hip

– 2ndry to corticosteroid use, SLE, RA,

• Injectables introduced for pts with dosing difficulties, inability to sit upright for 60 mins or swallow tablets

2nd and 3rd Generation – IV bisphosphonates

• Hypercalcaemia of malignancy

• Prevent metastatic tumours in breast, lung and prostate cancer

• Prevent bone complications and pain in multiple myeloma and kidney disease

• Prevent post-operative fractures and weakness in kidney, liver and cardiac transplant patients

Wonder Drug?• 19th most prescribed drug group

worldwide• Synthetic analogues of

pyrophosphates• Not metabolised• ½ absorbed dose is distributed to

bone• Increase bone density and thickness• Prevent tumours from removing bone

and spreading– Inhibit differentiation of bone marrow

cells into osteoclasts– Inhibit Osteoclast activity– Reduction in bone turnover and

resorption– Reduce local release of factors that

stimulate tumour growth

Side effects • Osteoclast function severely impaired

• Osteocytes not repaced• Capillary network in

bone not maintained• Bone becomes too

dense choking capillary network

• Avascular bone necrosis

• Osteonecrosis• Osteochemonecrosis• BON, ONJ

Incidence of ONJ in maxilla and mandible

• 3000 world cases– (191 million prescriptions)

• Mostly associated with intra-venous bis-phosphonates – Zometa (Zoledronic Acid)– Aredia (Palmidronate)

• Mostly following dental extractions or periodontal surgery

• Some spontaneously– Chronic infection– Trauma

Risk factors

• IV Bisphosphonate = higher risk for BON– 50% of dose is bio available for bone matrix

• Oral bis-phosphonate = low risk for BON– 1% dose of is absorbed by GI Tract

• Recent assessment test for necrosis potential– Arun Garg/Marx - Miami– C-Terminal Telopeptide (CTX) -– marker for serum

bone turnover– scores - controversial

• Time– Half life is 8-10 years

Co-risk problems– Immune-suppression

• Diabetes• HIV• Leukaemia• Transplants

– Drug Therapy • Corticosteroids• Chemo-therapy• Immune suppressants

– Age – SLE, RA & auto-immune

diseases – Clotting Disorders– Sickle cell Disease

Why a dental problem?

• Bis Ph. accumulate in high turnover areas

• Higher concentrations of drug in mandible than elsewhere

• After trauma or infection bone cannot respond adequately

• Masticatory Forces– Chronic Low Grade Trauma– Unable to repair micro-fractures

• Necrotic Bone• Bony sequestrum

Clinical Presentation

• Delayed or absent healing after extractions• Ragged Ulceration with bony base• Exposed or denuded bone

– May be symptomless unless 2ndry infection

• Mobile Teeth – may mimic periodontal disease• Bone Pain

– Chronic Pain– Heavy Jaw– Numbness

• Ref. to oral medicine clinic/Max Fax

Spontaneous necrosis in periodontal disease

Trauma from denture flange

Denuded mandibular torus

Presenting Complaint ulceration >3 months

Following extraction

Treatment• Clinical Management based on expert

opinion• No evidence base yet• Most post op treatment not effective

– Antibiotics– Withdrawing bis-phosphonate therapy– Hyperbaric oxygen– Surgical resection of necrotic bone

• Prevention is best option• Dental screening before patient commences

drug therapy

www.education!!!

• Education– Patient http://

www.ada.org/public/topics/osteonecrosis.asp– Dental Team

www.jada.ada.org– Oncologists/Medical Profession

www.jopasco.org Practical Guidelines for treatment of

osteonecrosis in patients with cancer. Journal of Oncology Practice 2006 Vol 2 Issue 1

Practice Points

Special Care Patients• Medical History

– Likely Pt groups • Post menopausal women• Patients with history of hip fractures• Osteoporosis• Pagets Disease• Breast cancer• Prostate Cancer• Lung Cancer• Multiple myeloma• Transplant Patients• Kidney Failure/Dialysis

Drug History/Route

• Oral Bisphosphonates – daily tablets– Actonel (Risendronate)– Boniva (Ibandronate)– Didronel (Etidronate)– Fossamax (alendronate) – Skelid (Tiludronate)

• IV Bisphosphonates – monthly injections– Zometa® (Zoledronate)– Aredia®) (Pamidronate) – Bonefos®/Loron® (Clodronate)

• Important to know how long drug has been taken

Fossamax

• 13th most prescribed drug in the world

• 170 cases BON worldwide (since 2006)

• No true cause-effect relationship• Extremely Low Risk BON• 0.7 cases per 100,000 person years

exposure

Dental management of patients receiving oral bisphosphonate therapy

• www.ada.org/prof/resources/topics/osteonecrosis.asp• Dentist should inform pt that low risk of developing

BON• Ways to minimise risk but not eliminate it• Good oral hygiene with regular dental care is best way

to lower the risk • Patients shown how to screen their mouths for signs • Routine dental treatment should not be modified• Alternatives to extractions should be offered • Non surgical periodontal management preferred• Care with fit of dentures

Fossamax – 8 years

Oral Surgery/Perio surgery

• Do not stop bis-phosphonate therapy• Informed Consent Form

– ADA website has template• Chlorhexidine rinse pre-op• Limit extraction or perio surgery to one sextant• Suture to prevent soft tissue trauma• Avoid packing – surgicell etc• Irrigation of socket with chlorhexidine post-op• No further surgery for two months to assess healing• Care with trauma from immediate dentures/splints• Post-op antibiotics only if co-risk factors

– Metronidazole 200mg tds for five days– Amoxycillin 500mg TDS for fourteen days– Or clinadamycin 300mg TDS for fourteen days

Aids to prevention• Inform patient of the consequences of oral

neglect• Xerostomia• Professionally applied products

– Cervitec• 1% Chlorhexidine• 1% thymol

• Home applied products– GC Tooth mousse

• Water Soluble mousse• Buffer which neutralises acidic saliva• Recaldent (Amorphous Calcium Phosphate)• Aids remineralisation• Applied with finger once per day

• Patients at higher risk of developing BON • Routine care as per oral bisphosphonate therapy• Tori – high risk area for trauma• Regular hygienist input encouraged but care with

mechanical intrumentation• Accidental trauma – recommend soft

toothbrush/changed often• Avoid extractions and periodontal surgery if at all

possible• Implants contra-indicated• Endodontics encouraged

Dental management of patients receiving iv bisphosphonate therapy

– risk of developing BON higher with time– risk of developing spontaneous BON

higher in presence of infection– risk of developing spontaneous BON

higher in presence of periodontal disease (grade 3 mobile)

– Risk greatest in mandible– Risk of developing BON higher with co-

factors

Risk assess surgery each case

Guidance for practitioners• Expert Panel JADA August 2006• No data from Clinical trials• Strict regime of post-op antimicrobials

and antibiotics (anecdotal)– To prevent secondary infection

• No withdrawing of drug pre-operatively unless specified locally

• Maximum 1-2 teeth extracted in one visit• Wait 2 months before repeat surgery

Dr Doctor • Liase with oncologist

– Information about the need for surgery• risks of providing and not providing care• Regime that you plan to use pre/peri and post op• Whether oncolgist would prefer to reduce/withdraw

drug pre or post operatively• FBC – check platelets

• Consent– Patients informed of risks involved with providing

and not providing treatment– Be honest –it is a gamble until the research is in

place– Involve the patient in the decisions.– Patient takes some responsibility for their dental

problem

Zometa 3 months – post ca breast

Pain and sinus LR6• Elective extraction

– IV bisphosphonates lower risk for first 3-6 months

– Patient finished chemo therapy• Protocol

– Pre-op• Liase with oncologist• FBC• Consent

– Peri-op• Pre-op chlorhexidine rinse• LA with adrenaline• No flap raised • De-coronated tooth sectioned and elevated roots

– Post op• Suturing to avoid trauma to soft tissues, vicryl• No packing (surgicell)• Metronidazole 200mg TDS for 5 days• 250-500mg amoxycilin TDS for up to two months

Patient and dentist relieved

• Patient irrigates socket with chlorhexidine BD for two months

• Review– 2 weeks– 1 month– 2 months

• Healed well with no complications

• Anecdotally, lower incidence of BON than expected in patients with few co-factors

Grade 3 mobile tooth

2 months post extraction

Chlorhexidine BD for three monthsAmoxycillin 250mg for two months

Soft Tissue – crown lenthening

Bony Sequestrum and Healing

• Non-invasive management

• Metronidazole and amoxycillin

• Chlorhexidine• 2 -3 months healing

time• Patients given syringe

and instructed to clean• Sequestrum tweezered

out in time

Endodontics

• Extremely high risk cancer patient

• No symptoms• XLA LR3 unavoidable• Endodontics LR12

– No instrumentation of apex

– Corsodyl post op (rubber dam)

– Decoronating and seal to avoid soft tissue injuries

– +/- Antibiotics– Fingers crossed

Difficult Scenarios highlighting problems to medics

• Male aged 52• Swelling LLQ• Multiple Myeloma• Diabetes• Undergoing chemo therapy• IV Bisphosphonate for 18

months• Post-extraction developed

osteochemonecrosis LLQ• Life saving bone marrow

transplant delayed• Oncologists have initiated

dental screening programme and information leaflets for patients

Future • Risk of treating patients taking oral

bisphosphonates is small!!• Will this increase in time (long half

life)• Price of dental neglect due to fear is

high• Regular routine and preventive care

essential• Perceived increased need for services

of endodontists• Most cases of BON occur in high risk

patients taking high risk drugs after dental surgery

• Guidelines updated regularly• Comprehensive oral evaluation on

patients starting therapy• New generation of effective drugs

avoiding BON

Thank you for listening

Notes available on

ISDH website soon