1. Drugs for Diseases of Bone
Vanderbilt Center for Bone Biology
Drugs for Diseases of Bone
Gregory R Mundy MD

2. Bone Remodeling
Trabecular
(cancellous)
Cortical
(compact)

3. Frost’s Contribution Osteoclastic Bone resorption New Bone Formation
Nature 1965:206, 489 Hattner et al

4. Analogy

5. Video courtesy of Dr. Susan Ott, University of Washington

6. Video courtesy of Dr. Susan Ott, University of Washington

7. Remodeling Sequence Same events in cancellous and cortical bone
Bone remodeling packets localized
Bone remodeling sequence prolonged (~3M)
Resorption and formation balanced
Thus, cellular events highly coordinated
Eriksen, 1986

8. Balanced Disease State
NORMAL
Pr. HPT.
Paget’s Disease
Thyrotoxicosis

9. Imbalance
Breast cancer, Myeloma
Prostrate cancer
Osteoporosis

10. 3 generations-screening for anabolic drugs

11. Normal
(age 20-50)
Osteoporosis
(age 60+)

12. Video courtesy of Dr. Susan Ott, University of Washington
Osteoporosis
Video courtesy of Dr. Susan Ott, University of Washington

13. Bone Disease in Cancer
Bone metastasis
Osteoporosis
Hypercalcemia

14. Skeletal-related events
bone pain
hypercalcemia
pathologic fracture
nerve compression syndromes
Cancer and Bone Metastasis
Lytic lesions

19. Fractures

20. Accelerating fracture repair
Model
3 month old healthy rats
Left femoral mid-shaft fracture
Outcomes –
X-rays, uCT
Biomechanical

21. Nanobeads Local – 2 Weeks
Drug NP
1.5ug lovastatin/day
Vehicle 6
Radiographic score
Average of two observers * * * 5 *
87%
73%
75% 4
52% 3
17% 2
The animal numbers (randomized)I used for the uCT are vehicle - 42,44,43,5 Nanobeads - 27,25,23,38 These are the number which appear on the web site 1
PBS
0.2
1.0
1.5
7.5
Nanobeads
(drug release ug/day)
* p< 0.05 compared to either PBS or nanobead control (no Lovastatin)