FARMAKOTERAPI OSTEOPOROSIS

Suharti K Suherman
Dept. Farmakologi & Terapeutik
FKUI
 TERAPI OSTEOPOROSIS
• Nonfarmakologi : perubahan life-style +
suplemen , dll.
• FARMAKOTERAPI 
*Hormonal Replacement Therapy(HRT)
*Selective Estrogen Receptor Modulator
*Bisphosphonate
*Calcitonin
*Recombinant Paratiroid : Teriparatide
Bone remodeling sequence in healthy subjects
 HRT  al. Estrogen (ERT)
• tulang estrogen
# meregulasi aktivitas osteoblast ;
# me ⇓ Σ & activitas osteoclasts.
# WPM  aktivitas osteoblast ⇓
 osteoclast >> active  OP

• ERT menstimulasi aktivitas osteoblast

 Indikasi

• u/ WPM  mencegah & terapi OP

• Kegunaan telah banyak dibuktikan 
tetapi mengingat ESO yg serius
apalagi, jangka lama 
 Estrogen replacement therapy
• Women Health Initiative study (WHI)
randomized controlled trial,first
proved HT ⇓ incidenc of all OP-
related fractures in PMW
• later study concludedserius SEs >
benefits on bone  a significant ⇓
in HT use for PMW with OP
•  HT was not used as 1st-line th/ for
OP & fracture
Levin V .A, et.al.. Estrogen th/ for osteoporosis in the modern era. Osteoporosis
International (2018) 29:1049–1055
. Later studies  challenged these &
have shown significant efficacy of
HT in various doses, durations,
regimens, & routes of administratn
These studies support that HT improves
BMD & ⇓ fracture risk in ♀ with &
without OP

& suggest that low-dose transdermal

HT are less likely associated with
the SEs of breast -Ca,
endometrial hyperplasia, CAD &
VTE previously observed in
standard-dose oral HT regimens.
• Given the need for Estr in PMW & evidenc
supporting the cost effectiveness,
safety, efficacy , we propose that
HT should be considered for the
primary prevention & Th/ of OP
in appropriate candidates.
• lower-dose & transdermal that have
been shown to be safer than oral
standard-dose HT.
•
• low dose transd 17β Est (14μg/day) mono
th/for 2 yrs  a significant ⇑ in BMD &
prevention of bone loss without ⇑ risk
of endometr hyperpl &vaginal bleeding
compared to placebo
• 17β- estradiol transdermal patch  slow,
sustained release of the hormone,syste
matic distribution, & more constant
blood levels than oral dose
•  + vit D + Calcium + physical exercise
• Levin ER,et al. Estrogen, Progestin, & the Female Reprod Tract. In: GG, 13th
ed. 2018.McGraw-Hill, 803–830.
 SELECTIVE ESTROGEN RECEPTOR
MODULATOR = SERM
• senyawa dg : tissue-selevtive activity
• SERM yg telah disetujui FDA
• Generasi - 1 : tamoxifen
- 2 : raloxifen (RLX)
- 3 : bazodoxifen

Nolin TD & Friedman PA. Agents affecting mineral ion homeostatis & bone turnover.
GG,13th ed, 2018.887.
SERM  raloxifen : menghambat
resorpsi tulang , tanpa stimulasi
mammae
Indikasi : th/ & pencegahan osteoporosis
pd WPM
& ternyata ⇓ resiko invasive
breast-Ca (in high risk PMW)

Bikle DD. Agent that affect bone mineral homeostasis. In ; Bestram G

Katzung,editor. Basic & Clinical Pharmacology, 14th ed. McGrawHill,, 14th
ed.2018, 772-791.
Seung S K, et.al. Treatment of osteoporosis & ⇓ in risk of invasive breast-Ca in
PMW with raloxifene Expert Opin Pharmacother. 2011 March; 12(4):
 Studi RLX
• 3 studi besar :
1.Multiple Outcomes of Raloxifene Evaluation
(MORE, 1999, 2002),
2. Continuing Outcomes Relevant to Evista
(CORE, 2004, 2005)
3. Raloxifene Use for The Heart (RUTH, 2006)
 RLX tdk hanya atasi osteo- penia / porosis
WPM, tetapi juga ⇓ kejadian fraktur
vertebra / nonvertebra & insidens Ca-
mammae
• Kemudian 2 studi lain
a. Study of Tamoxifen & Raloxifene
(STAR, 2006)  terbukti efektivitas RLX
= tamoxifen dlm cegah Ca-mammae
b. Evista Versus Alendronate (EVA trial,
2007) : efektivitas RLX = alendronat
dlm me ⇓ insidens fraktur osteoporosis
Studi-2 tsb memberikan highlight  RLX
berguna u/ pencegahan & th/osteoporo
sis WPM & u/ pencegahan estrogen-
related breast cancer
• Penggunaan dimonitor, mungkin timbul
ESO al. thromboemboli;
hasil meta-analisis  resiko deep
vein thrombosis (DVT),
pulmonary embolism (PE);
 karenanya kontra-indikasi u/ WPM
dgn/pernah alami thromboemboli,
meski rx tsb > banyak terjadi pd
WPM di US & Eropa;
di Asia >sering terjadi gangguan GI
 BISFOSFONAT
Potensi anti resorpsi 3 generasi
Chemical Antiresorptive
Generation Examples potency
modification
First Short alkyl or halide Etidronate 1
side chain Clodronate 10

Second Cyclic side chain Tiludronate 10

Amino-terminal Pamidronate 100
group Alendronate 100-1,000

Third Cyclic side chain Risedronate 1,000-10,000

Ibandronate 1,000-10,000
Zoledronate 10,000+

Reprinted with permission from WattsEndocrinol

NB. Metab Clin
North. Am
1998;27:419-439.
 Farmakologi Bisfosfonat
• Bone-seeking
• Efektif pd pemberian oral
atau IV
OH R1 OH
• Absorpsi oral  buruk
O = P— C— P = O • Tidak dimetabolisme,
ekskresi melalui ginjal
OH R2 OH
• Retensi ditulang cukup
lama
• Side chain determines
potency & side effects
 Mekanisme kerja
• Hambat aktivitas osteoclast progenitors
• Hambat Osteoclast recruitment
• Merangsang apoptosis mature osteoclast
• Efek antiapoptotic pd osteoblast &
osteocytes
• Indikasi : osteoporosis  PMW atau
andropause
• Efek samping : gangguan sal cerna ;
arthralgia, myalgia, flu-like syndr ;
rx lokal pd tempat infus, rx alergi
umum (jarang)
• Efek samping yg serius : ONJ (jarang);
BP th/  subtrochanteric femur
fracture in longterm recommend a
“drug holiday” after 5 yrs of th/
and 3 yrs for zolendronic acid
 Preparat :

• Risedronat  5mg/h atau 35mg/mggu

Alendronat  10mg/h atau 70mg/mggu
Ibandronat  150mg/bln  oral
3mg/3ml IV bolus/3month
Zolendronic acid  ; 5mg /100ml/ thn
 Calcitonin

• hormone produced by parafollicular C

cells
• A single chain peptide hormone  IM /
nasal spray
• Postmenopausal oeteoporosis 
calcitonin inhibit osteoclast activity
in bone resorption osteoclast
↑ BMD = Bone Mineral Density)
  enough intake Calcium & vit D
• Preparations : synthetic salmon
calcitonin  nasal spray 50 IU
2x/ day or injection ampul 50 IU
 1 x / 2 days

• Adverse reactions : nausea, flushing,

dose-dependent
• Hati-hati efek samping kanker hepar