Lecture 50 Bone Drugs Bisphosphonates

Front 1

1. Describe the uses of alendronate, risedronate and ibandronate.

Back 1

• Oral bisphosphonates are approved for the treatment and prevention of osteoporosis in postmenopausal females.
• Alendronate (Fosamax) is also approved to treat osteoporosis in males.

Front 2

2. Describe the mechanism of action of alendronate (Fosamax), risedronate (Actonel) and ibandronate (Boniva)

Back 2

• Oral bisphosphonates: mechanism of action
o Inhibits bone resorption by shutting down osteoclastic activity or by inhibiting precursors to osteoclasts. This results in a decreased turnover of bone.
o Decreases the rate of bone resorption resulting in increases in bone mineral density.

Front 3

3. Describe the use of palmidronate (Aredia) and zoledronic acid (Zometa).

Back 3

• IV bisphosphonates: Palmidronate (Aredia) and Zoledronic acid (Zometa)
o Used to treat hypercalcemia of malignancy
o This syndrome appears in certain cancers such as breast cancer, multiple myeloma, prostate cancer
o These bisphosphonates are used to prevent the loss of calcium from bone thus preventing the hypercalcemia
o Aredia administered as monthly IV over 2 hours OR Zometa administered as monthly IV over 15 minutes; either for at least 9 months or longer

Front 4

4. Describe the warning by the FDA on bisphosphonates and osteonecrotic jaw (ONJ).

Back 4

• Reports in Oral Surgery literature in 2003 reported an association with use of these bone drugs and appearance of ONJ
• FDA and Novartis Pharm 2004
o Issued warning labeling on Aredia and Zometa to all dental health professionals
 Prior to therapy, dental exams must be performed to ensure good dental health
 All odontogenic infections must be treated and cleared up
 All exdontia performed if necessary

Front 5

5. List the symptoms of ONJ.

Back 5

• Protruding jaw bone
• Affected bone is avascular
• Necrotic tissue
• Non-cancerous
• Precipitated by tooth extraction
• Non-healing extraction sites

Front 6

6. Describe the frequency of ONJ cases associated with the use of IV bisphosphonates

Back 6

• Approximately 10% of cancer patients receiving Zometa will acquire ONJ after 9 month exposure
• Approximately 4% of cancer patients receiving Aredia will acquire ONJ after 9 month exposure

Front 7

7. According to the ADA what is the frequency of ONJ cases associated with the use of oral bisphosphonates?

Back 7

• Risk of developing ONJ remains low for patients taking orals
• Routine dental treatment need not be modified based on oral BP use
• Patients should not alter use of oral BPs without consulting their doctors
• Need to develop screening tools to predict patients’ risk (we can’t predict the risk)
o OJO (exam): 1 case out of 140,000 person life years exposure to orals (ADA 2006)

Front 8

8. What is Reclast, how is it used?

Back 8

• Zoledronic acid under the brand name of Reclast has been approved as a once annual 15 minute IV of a dose of 5mg to prevent osteoporosis.
• This dosing was associated with a significant improvement in bone mineral density and bone metabolism markers. It is unknown whether this dosing schedule places the patient at risk for ONJ; however, data do show a higher risk of serious atrial fibrillation in patients receiving Reclast compared to patients receiving placebo.
• There is probably no risk at all for developing ONJ with this drug (and Boniva)