Antiresorptive-Induced Osteonecrosis

Question 1

-_______ is preventable and treatable

Answer 1

-Osteoporosis

Question 2

Drug Stimulators of Bone Formation

• ____(Teriparatide): Induces Osteoblast proliferation and survival, but is still in _____ use and requires daily _____
• ______ _____ (Protelos): Dual action effect on Osteoblasts & Osteoclasts, but is still in _____ use, and is used in ______
• _______ _____ ___ (Sclerostin): Induces bone formation via enhancing ________ proliferation and differentiation, but is only in Phase ____

Answer 2

• PTH 1-34; clinical; injections
• Strontium Ranelate; clinical; Europe
• Antibody AMG 785; 3

Question 3

-_______: Negative side effect of anti-______ drugs used to treat Osteoporosis that leads to bone ______

Answer 3

-Osteonecrosis; anti-resorptive; necrosis

Question 4

Drug Bone Resorption Inhibitors

• ________: Blocks the differentiation of Osteoclast Precursors into Osteoclasts
• ______ _____ _____ (Raloxifene): Inhibits Osteoclast function, and is in clinical use ______
• ________ (Alendronate, Zoledronate): Inhibits Osteoclasts, and is in clinical use _______
• ______ ____(Denosumab): Inhibits Osteoclast development and function by binding to ____ so Osteoclasts can’t form, and is in clinical use with _____ injections
• _____ ______ (Odanacatib): Inhibits the release of ________: dissolves the bone matrix, and is in Phase _

Answer 4

• Estrogen
• Selective Estrogen Mimic; once daily
• Bisphosphonates; once weekly
• RANKL Antibody; RANKL; bi-annually
• Cathepsin K Inhibitor; Cathepsin K

Question 5

Bisphosphonates

• __________ analogues where the central _______ is replaced with a _______ and 2 different side radicals
• __________ contains many ________ allowing bisphosphonates to take their place
• ______ end binds and anchors to ________, forming ______ compounds
• The backbone is resistant to ______, ______, and _____ hydrolysis
• The side ______ impact the drug effects
• Many contain _______, and those that due are more ______ and cause ________. They inhibit ____ ____ ____: Responsible for the synthesis of Farnesyl Diphosphate used in the synthesis of _______ & ______
• Can block the recruitment of _______ by ________
• Can also lead to _____ to other bones leading to fractures too

Answer 5

• Pyrophosphate; Oxygen; Carbon
• Hydroxyapatite; pyrophosphate
• Phosphate; Hydroxyapatite; insoluble
• Heat; chemicals; enzymatic
• Radicals
• Nitrogen; potent; Osteonecrosis; Farnesyl Diphosphate Synthesis; Cholesterol & Isoprenylation
• Osteoclasts; Osteoblasts
• Necrosis

Question 6

Action of Denosumab

• Anti-_____ antibody that inhibits _______ formation & activation
• _____ is expressed by Osteoclast Precursors
• _____ is expressed by Mesenchymal Stem Cells and Osteoblasts
• Incidence of _______ fracture decreased in patients who too Denosumab: ____% reduction if fracture risk, and ____% decrease in ____ fractures

Answer 6

• RANKL; Osteoclast
• RANK
• RANKL
• Vertebrae; 68%; 40%; hip

Question 7

Cathepsin K Inhibitor (_______)

• Prevents Osteoblastic bone matrix _______
• ____ action
• Will preserve osteoclast functions but result in _____ resorption surfaces, making them less _____ without ____ them like Bisphosphonates.
• ________ resorption still allows for the release of ______ factors to attract _______ for bone formation
• Reduce bone _____ while increasing bone _____

Answer 7

• Odanacatib
• Degradation
• Shallow; effective; killing
• Decreased; Osteogenic; Osteoblasts
• Resorption; formation

Question 8

Antiresoptive-induced Jaw Osteonecrosis

• Caused by taking _______, but people still need to take them for other bone-related diseases like _______
• Only effects the _____ and not other bones
• ______ & ______ Cancers can result in the degradation of bone
• Difficult to identify bone loss on _________
• Can occur ________

Answer 8

• Bisphosphonates; Osteoporosis
• jaw
• Breast & Prostate
• Periapicals
• Spontaneously

Question 9

Osteonecrosis of the Jaw Precipitating Factors
Drug Related:
-Type of \_\_\_\_\_\_\_\_\_\_ & dose
-\_\_\_\_\_\_
-Diffusion of \_\_\_\_\_\_
Local Risk Factors:
-Dental \_\_\_\_\_\_\_\_ & \_\_\_\_\_\_\_\_\_
-\_\_\_\_\_\_\_/Osseous surgery
Local Anatomy:
-Twice as likely to occur in the \_\_\_\_\_ than the \_\_\_\_\_
-\_\_\_\_\_ \_\_\_\_/Exostoses
-\_\_\_\_\_\_\_\_\_ ridge
-Thin \_\_\_\_ \_\_\_\_\_
Oral Diseases:
-\_\_\_\_\_\_\_\_\_\_\_ disease
-Peri-apical \_\_\_\_\_\_\_
-Poor \_\_\_\_ \_\_\_\_
Other Factors:
-\_\_\_\_\_\_\_
-\_\_\_\_\_\_\_ therapy
-\_\_\_\_\_\_\_\_ drugs
-\_\_\_\_\_\_\_ & \_\_\_\_\_\_\_ use

Answer 9

Drug Related:
-Antiresorptive
-Potency
-Therapy
Local Risk Factors:
-Implants & Extractions
-Periodontal
Local Anatomy:
-Mandible; Maxilla
-Palatal tori
-Mylohyoid 
-Oral Mucosa
Oral Diseases:
-Periodontal
-Abscesses
-Oral Hygiene
Other Factors:
-Diabetes
-Corticosteroid 
-Chemotherapeutic 
-Smoking & alcohol

Question 10

Other Drugs Associated with Osteonecrosis of the Jaw

• ______(RANKL Antibody)
• _______ (Avastin): An anti-VEGF-A
• _______(Sutent): Receptor Tyrosine Kinase inhibitor

Answer 10

• Denosumab
• Bevacizumabe
• Sunitinib