BISPHOSPHONATES

MECHANISM OF ACTION OF
BISPHOSPHONATES
Bisphosphonates are the class of agents that
inhibit bone resorption and thus bone renewal by
suppressing the recruitment and activity of
osteoclasts, thus shortening their life span.
The mechanism of action of bisphosphonates is
by binding to bone mineral, where they are
concentrated and accumulate over time.
Bisphosphonates also have antiangiogenetic
property and may be directly tumoricidal.
 Bisphosphonate are given orally and intravenously.
Oral bisphosphonates
1. Alendronate
2. Etidronate
3. Risedronate
4. Tiludronate
5. Ibandronate
. Oral bisphosphonates are used in patients with
osteoporosis.
 Injectable bisphosphonate
1. Pamidronate
2. Zolendronic acid
3. Clodronate
. Injectable bisphosphonates are used in patients with
cancer who have primary lesion of bone or skeletal
metastasis.
NON-NITROGENOUS
BISPHOSPHONATE
Non-N-containing bisphosphonates:

Etidronate(Didronel)

Clodronate(Bonefos,

Loron)
Tiludronat
NITROGENOUS BISPHOSPHONATE
N-containing bisphosphonates:
Pamidronate(APD, Aredia)

Neridronate(Nerixia[39])
Olpadronate 500
Alendronate(Fosamax)
Ibandronate(Boniva)
Risedronate(Actonel)
Zoledronate(Zometa,Aclasta)
CLINICAL USES OF
BISPHOSPHONATE
1. Paget disease
2. Fibrous dysplasia
3. Osteoporosis
4. Ostegenesis imperfecta
5. Multiple myeloma
6. Primary hyperparathyroidism
7. Multiple myeloma
MECHANISM OF ACTION OF BONJ
Exact mechanism of action is unknown.
Bisphosphonate bind to the bone and incorporate

in the osseous matrix.

During bone remodelling, the drug is taken up

osteoclasts and internalized in the cell cytoplasm

where it inhibits osteoclastic function and
induces apoptotic cell death.
Bisphosphonates also inhibit osteoblast-mediated
osteoclastic resorption.
 Antiangiogenetic properties.
BOJ results from a complex interplay of bone
metabolism, local trauma, increased demand for bone
repair, infection and hypovasculariy.
Patients receiving bisphosphonate are more
susceptible to BONJ than are those receiving the drug
orally.
CLINICAL SIGNS AND SYMPTOMS
OF BONJ

Stage 0No exposed necrotic bone

Stage 1 Exposed and necrotic bone where patient is
asymptomotic and has no evidence of infection.
Stage 2 Exposed and necrotic bone in patients
showing pain, infection, erythema around the necrotic
bone,+/- discharge.
 Stage 3 Exposed and necrotic bone in patients
showing pain, infection resulting in pathological
fracture, oro-antral fistula, oro-antral communication,
extra oral fistula or osteolysis extending to the lower
border of mandible or sinus floor.
DENTAL CARE BEFORE TAKING
BISPHOSPHONATE
Patients receiving bisphosphonates have BONJ
spontaneously. The majority of affected patients
experience this complication following routine
dentoalveolar surgery i.e; extraction, dental
implant or apical surgery.
Teeth with a poor prognosis should be removed
before bisphosphonate administration or as early
as possible after institution of treatment.
 If possible, institution of bisphosphonate therapy
should be delayed for approx 4-6 weeks after invasive
procedures, such as dental extractions to give the bone
a chance to recover.
Dental prophylaxis, caries control and conservative
restorative dentistry are critical to maintaining
functionally sound teeth.
DENTAL CARE FOR PATIENTS WHO
ARE TAKING BISPHOSPHONATE
Elimination of all potential site of infection must
be primary objective of this consultation.
Restorative dentistry should be performed to
eliminate caries and defective restoration.
Crown and fixed prosthodontic work may not be
appropriate for some patients.
Periodic followup visits should be scheduled.
DENTAL CARE FOR PATIENTS
WITH BONJ
Treatment should be eliminating or controlling
pain.
Preventing progression of the exposed bone.

Several treatment modalities for BONJ are

reported in the literature and include minor

debridement under local anaesthesia, major
surgical sequestrectomies, marginal and
segmental mandibular resection, partial and
complete maxillectomies and HBO therapy.