Anti-Resorptive Medication Related Osteonecrosis of the Jaw

Question 1

 Initially used for the treatment of osteoporosis,
Paget’s disease, and osteogenesis imperfecta
 More recently, they have been used as an
adjunctive treatment of cancer
 Decrease osteoclastic activity

Answer 1

Bisphosphonates

Question 2

 Oral only
 Etidronate –Didronel
 Clodronate –Bonefos, Clasteon, Loron
 Primarily used for the treatment of Paget’s disease
 Low potency
 Prevents osteoclast proliferation by inhibiting ATP
(adenine triphosphate) dependent enzymes

Answer 2

Non nitrogen bisphosphonates

Question 3

 Oral or IV
 Mechanism of action
 Prevents binding of essential proteins to the cell
membrane leading to apoptosis
 Prevents adhesion of the osteoclasts to the
hydroxyapatite crystals by altering the cell cytoskeleton

Answer 3

Nitrogen containing bisphosphonates

Question 4

 Osteoporosis –Prolia –60mg/6 months
 Bone Metastases –Xgeva –120mg/4 weeks
 Mechanism of action
 Tumor cell promote the release of RANK Ligand from
the osteoblast within turn promote the production of
osteoclasts
 Denosumab binds to the RANK Ligand an prevents
osteoclast proliferation

Answer 4

 Denosumab (Monoclonal antibody)

Question 5

 Mechanism of action
 Recognizes and blocks vascular endothelial growth
factor (VEGF), a protein necessary for angiogenesis
 Used in the treatment of gastrointestinal tumors,
renal cell carcinomas, and neuroendocrine tumors

Answer 5

Antiangiogenic meds

Question 6

___% of the bisphosphonate is excreted by the kidneys

within hours of ingestion or infusion

Answer 6

50%

Question 7

Remaining____% deposited in the skeleton

Answer 7

50

Question 8

 Make up 85% of resting bone
 Have a long life span
 Have a low affinity for bisphosphonates
 Bisphosphonates loosely bind to the surface and are
removed within day

Answer 8

Osteocytes

Question 9

 Make up 2-4% of resting bone
 Have a life span of 2 weeks
 8x the affinity for bisphosphonates
 Upon death of osteoclasts, bisphosphonates are
reabsorbed by the skeleton or excreted by the kidneys

Answer 9

Osteoclasts

Question 10

 Make up 10-12% of resting bone
 Have a life span of 2 months
 4x the affinity for bisphosphonates
 Bisphosphonates are incorporated into the bone instead 
of being released

Answer 10

Osteoblasts

Question 11

HOw many months pre and post surgical should there be a drug holiday for bisphosphonates?

Answer 11

2 pre; 4-8 months post