1. 11/24/2018
OSTEOPOROSIS

2. Bisphosphonates: General Molecular StructureOH C R1 P O
When R1 is an
OH group, binding to
hydroxyapatite is enhanced
The P-C-P group is essential
for biological activity
R2 = -CH3 = etidronate
R2 = -CH2CH2CH2NH2 = alendronate
R2 = -CH2CH2NH2 = pamidronate
R2 = -CH2-3-pyridine = risedronate
The R2 side chain
determines potency
P-C-P acts as
“bone hook”
and is essential
for binding to
hydroxyapatite
Reprinted with permission from Russell RGG, et al. Osteoporosis Int. 1999;(suppl 2):66-80.
11/24/2018
OSTEOPOROSIS

3. Bisphosphonates: Pharmacokinetics
Russell R, et al.
Osteoporos Int.
1999;
(suppl 2):S68-80.
Intestinal
absorption is
low: 0.5%-10.0%
Food (eg, Ca) interferes with absorption
Fast and “complete” uptake into bone: 20%-80%
Bisphosphonates:
Pharmacokinetics
Urine is main route of
elimination; no metabolites
Slow release
from bone
No biliary
secretion
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OSTEOPOROSIS

4. Bisphosphonates RISEDRONATE IBANDRONATE ZOLEDRONATE ALENDRONATECH 3 P C O HO OH Cl 2 NH N
(CH ) 4 H S
ETIDRONATE
PAMIDRONATE
ALENDRONATE
IBANDRONATE
RISEDRONATE
TILUDRONATE
CLODRONATE
ZOLEDRONATE
Bisphosphonates
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OSTEOPOROSIS

5. reduce the risk of fracture
Bisphosphonates
maintain bone mass O
reduce the risk of fracture O
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OSTEOPOROSIS

6. FDA Approves Once-Weekly Tablets of Fosamax® for Treatment and
Prevention of Postmenopausal
Osteoporosis
Oct. 23, 2000
   Two new dosage strengths of Fosamax®
(alendronate sodium) have been approved
as once-weekly tablets: 70 mg for the
treatment of postmenopausal
osteoporosis  and 35 mg for the prevention
of postmenopausal osteoporosis. 
11/24/2018
OSTEOPOROSIS

7. FDA Approves a new 35 mg Once-Weekly dosage strength of Actonel® for the Treatment and Prevention of Postmenopausal Osteoporosis
May. 20, 2002   
11/24/2018
OSTEOPOROSIS

8. … and always remember ... … to stay up right …
11/24/2018
OSTEOPOROSIS