For the programme book

PHARMACOLOGICAL
MANAGEMENT OF
OSTEOPOROSIS
DRUGS FOR TEATMENT OF
:OSTEOPOROSIS
.calcium-1 •
.vitamin D-2 •
:Antiresorpitive Drugs-3 •
a-calcitonin.
.b-Bisphosphonates
c-SERMS.
.Bone forming agents-4
.Dual acting Bone agents-5
CALCITONIN
:Bisphosphonates
.Etidronate
.Alendronate
.Residronate
.Zoledronic acid
 Important structural elements of
bisphosphonates

When R is an OH
1

group, binding to
hydroxyapatite is
enhanced OH R 1
OH

O P C P O

P-C-P is essential
OH OH
for binding to
hydroxyapatite
R 2

The R side chain

2

determines potency.
Nitrogen-containing
bisphosphonates
are most potent

Adapted from Russell G, et al. Osteoporos Int. 1999;(Suppl. 2):S66–80

 Bisphosphonate
Cellular and Molecular Mechanisms of Action

BP BP HMG Co-A

Mevalonate
BP BP BP N-Bisphosphonates

Farnesyl-PP Geranylgeranyl-PP
Active Inactive Apoptotic
Osteoclast Osteoclast Osteoclast
Isoprenylation
Squalene

Cholesterol
 Risedronate Sodium

Third Generation Bisphosphonates

R1 OH
O O
HO P C P ONa
OH CH2 OH

2.5 H2O
N R2
increased Potency20
and reduced GIT s/e
 Molecular Structure of Zoledronic Acid
Zoledronic acid is a potent nitrogen–containing –
bisphosphonate
)Core bisphosphonate moiety (red arrows •
)R2 side chain: imidazole ring (blue arrows •

N O OH
N P
O C OH
P OH
HO OH

Green JR, et al. J Bone Miner Res. 1994;9:745-751.

II-Bone forming agents:
: Teriparatide
 : Teriparatide

Is a recombinant human parathyroid

hormone acting as an anabolic agent. It
stimulates now bone formation. It is also
claimed to increase resistance to fragility
farcture. The recommended done is 20
micorgrams injected subcutaneously once
dialy. Patient taking Teriparatide must receive
special training on the injection technique.
The maximum total duration of treatment is
restricted by licence to 18 months in Europe
and 24 months is USA.
:Dual acting bone agents

:Strontium Ranelate
 ?What is Strontium Ranelate

An
innovative,
synthesize
d drug

This compound contains 2 ions of stable •

(non-radioactive) strontium per molecule and
)an organic moiety (ranelic acid
 OPG, RANK, RANKL: an essential link
between
Osteoblast and Osteoclast Differentiation

Differentiation and fusion

Osteoclas
t
Progenito OPG
RANK Osteoclas
r
t
RANK L
RANK L
Osteoblast /
Stromal cell

BONE

Adapted from Khosla. Endocrinology. 2001;142(12):5050.

 .Management of C.I.O
•Consider using inhaled Corticosteroids whenever possible.

• It is recommended that supplementation with Calcium

Carbonate sufficient to ensure a daily consumption of 1500 mg (or
equivalent) daily and vitamin D of 800 IU dialy may preserve bone mass in
patients receiving long-term treatment of Corticosteroids.
•Inhibit CIO with pharmacotherapy:

• Bisphonnates in addition to vitamin D and Calcium ate effective in both

prevention and treatment of CIO.

•Second line therphy include Hormone Replacement therapy in women

and testosterone in men, calcitonin and thiazide diuretics. Patients who
have a urine Calcium excretion > 300 mg/ 24 h may benefit from the
addition of a thiazide diuretic ( e.g: hydrochlorthiazide 25 mg/day)
•