CORTICOSTEROID-INDUCED

OSTEOPOROSIS

R. Djokomoeljanto
Bagian Ilmu Penyakit Dalam
Fakultas Kedokteran Undip
Semarang

De Laet CED & Pols HAP. (2000)

Osteoporosis is defined as a condition characterized
by low bone mass and micro-architectural
deterioration of bone tissue, with a consequent
increase in bone fragility and susceptibility to
fractures.

Increasing age bears consequence of increased fracture.

Rates in men are lower and at a later age than in women.

There is also an increasing trend in epidemiological

observation

There are a number of risk factors that leads

to osteoporotic fracture are :
a. Bone aspects (bone strength, bone mass, quality
macro structure, extraskeletal factors, minerals.
b. Trauma leading to fracture
c. Endocrine factors (-E2, -androgen, -calcitonin)
d. Dietary factors (lactose int, calcium, vitamin D)
e. Inactivity, immobilisation or exercise
f. Drugs use (steroids ?)
g. Genetic factor

BMD: the lower the more prone to fracture

Menopause and bone mineral density

Calcium intake and fracture

Calcium protects people from fracture

Factors affecting rate of bone loss

Nutrition

Bodyweight

Life-style

Genetic

Sex
hormon

Diseases
Cushing S
Clucocort th
Hyperthyroidi
sm
Diabetes M

Increase
bone loss

Protein
Alcohol
Caffeine

Thinness

Inactivity
Cigarette sm
Bedrest

Positive
family histr
Female sex

Early menop
Oophorect.
Postmenop.
Amenorrhoe

Decrease
bone loss

calcium

Obesity

High activity

Race (black)

Pregnancy

Unknown
effect on
bone loss

phosphate

Normal activity

Osteoporosis :

Primary or evolution :
osteoporosis type I (postmenopausal)
osteoporosis type II (senile)

Secondary: IDDM, hyperthyroidism, Cushings

corticosteroid induced, anticonvulsant etc

The characteristics of OP type I and

OP type II
Characteristics

Female / male ratio

Range of age
The affected bone
Fracture predisposition
Type of bone loss
Parathyroid function
Main patophysiology
Main factor
Calcium need in the diet

Type I
(postmenopausal)
6:1
51 65
trabec > cortic
spinal, radius
fast, accelerated
decrease
resorption >
estrogen loss
low

Type II
(senile)
2:1
75
trab=cort
hip
gradual
increase
formation <
ageing
important

Risk factors for postmenopausal

osteoporosis (OP-1)
Women

Corticosteroid treatment

Postmenopausal

Anticonvulsant treatment

Pale white skin

Hyperparathyroidism

Premature menopause (surg?)

Thyrotoxicosis

Positive family history

Smoking

Nullipara

Alcohol abuse

Gastrectomy, small stature

Inactivity

Pathophysiology of osteoporosis (A)

Activation of resting OB on the surface of bone and stromal marrow.

Release of cytokines, m-CSF,TGF-, TNF enhance recruitment of MNgiant cells to become bone-resorbing cells (OC). Inhibited by OPG.

Pathophysiology of osteoporosis (B)

OPG being to act as a dummy receptor for the OPG ligand (=OPGL,
RANKL). OPGL bind RANK-rec.activator initiate OC activation and
subsequent bone resorbtion.

The remodelling cycle. A: resting trabicular surface, B:

osteoclast dig a cavity, C: completion of resorption, D:
recruitment of osteoblast, E: secretion of new matrix, F: matrix
with calcification, G: completion of mineralization of new matrix

Osteoclast formation requires various growth & differentiation

factors. Eg : OAFs, PTH, 1,25D

Osteoclast mediated bone resorption.

It attaches to bone surface via integrin-mediated binding to bone matrix

bone proteins. Secreted into the sealed space are acid and enzymes forming
an extra cellular lysosome.

The use of BMD and biochemical marker of

bone remodelling:
a. BMD assess the risk of fracture (S-DPA, DEXA, Q-CT)
Estimate the bone mass , mineral and its density
WHO score : women, proximal femur, DEXA ( 2.5> SD treat!
30% of whom become osteoporotic.
b. Markers assess the ongoing process resorption or formation
Resorption markers: HyPro, Pyridinoline and Deoxy-P (PYD)
collagen cross-linked N-telopeptide (NTX)
Formation markers: osteocalcin, BSAP, PIPC

Corticosteroid induced osteoporosis:

Due to excessive dose
In RA treated with CS 1/3 get fracture (cf.16-22% control)
In Children CS skeletal growth impairment
In adults resorption formation imbalance occurs
Axial bone loss more than appendicular (peripheral) loss.
( 40% versus 20% hence the vertebal compression)

Corticosteroid induces resorption by:

o
o
o
o
o
o
o
o

New osteoclastogenesis (ODF while OPG )

Osteoblast formation and function hampered
CS regulates the collagenase (MMP-1 and 3)
CS high dose inhibit calcium resorption from the gut
CS impair renal calcium resorption (Na, HCT)
CS PTH stimulation Ca from the bone
CS increases the apoptosis of ostoblast
CS inhibit the gonadotropin secretion hypo.

Corticosteroid induced osteoporosis:

Corticosteroid dose
(corticosteroid induced osteoporosis CSIOP)

Longterm use of prednison > 5 mg/d CSIOP

High dose CS for acute dermatis in O.K. but
Small dose of CS in rheumatoid arthritis does !
Beclomethazon proprionate 2 dd 500 g decrease
intestinal calcium absorption by 12%
Hydrocortison substitution < 15 mg is safe
Prednisolon 2.5-7.5 mg is a risk for spine / hip fracture

How to prevent the CSIOP

Reducing the dose or looking for alternatives
o Alternate dose protect children from growth failure
o Alternate dose in adults does not protect CSIOP
o Calcium (1500 mg) and vitamin D (400-800 IU/day)
o Mind the hypercalciuria
o Encourage physical activity
o If no contraindication : HRT
o

Treatment of CSIOP
Anti-resorptive therapy: calcitrol and calcitonin
bisphosphonate treatment (alendronate 5-10 mg daily for 48
weeks increases spine / hip BMD
Bone promoters. PTH as true-bone-anabolic effect The most
active part of PTH is hPTH (1-34) improves lumbar BMD as
high as 35% (CT trabecular) or 11% (DEXAtrabecular and
cortex) trabecular bone is very responsive to PTH
treatment
HRT improves slightly.

Relation between dose, duration of prednsion

administration and adrenal suppression
Duration
Dose and schedule

1 week

1 month

6 months

1 year

5 years

Replacement(<7.5
mg/day)

+/-

Alternate day (any

dose)

10 mg /day

+/-

++

15 mg/day

+/-

++

+++

20 mg/day

+/-

++

+++

+++

>30 mg/day

++

+++

+++

+++

. medication > one week risk of HPA

. morning daily dose is more physiological
. longacting CS (dexa) exerte more suppression than biological ones ( HC, Pred.)

Summary
Osteoporosis is the disease of tomorrow. The consequence
is incapacitating and costly
Prevention program is the most effective way. By increasing
the peak-bone-mass, adequate calcium intake, weight bearing
exercise, regulate the good diet, avoiding drugs that is known
to cause osteoporosis osteoporosis can be prevented. This
disorder affect mosly postmenopausal women. Care must be taken
with corticosteroid treatment. Highdose which is shown by the
depressed pituitary function may cause corticosteroid induced
osteoporosis
Although prvention is better than cure, varios medications
Are now available that effectively treat or prevent osteoporosis
By understanding the pathophysiology of osteoporosis it is
expected that rational use of treatment will be followed.