STEROID-INDUCED OSTEOPOROSIS

Supervisor
dr. Karya Triko Biakto, Sp.OT (K-Spine)


Orthopaedic and Traumatology Department
Medical Faculty of Hasanuddin University
Spine Division
Andriessanto Lengkong
Reference Reading
Osteoporosis Definition

A systemic skeletal disease characterized by
low bone mass and microarchitectural
deterioration of bone tissue, with a
consequent increase in bone fragility and
susceptibility to fracture.

Normal Bone vs Osteoporotic Bone
Loss of trabecular plates (right) results in weakened
bone structure significantly increasing risk of
fractures.






Primary vs Secondary
Osteoporosis
Primary
Postmenopausal
Decreased estrogen results in increased osteoclastic
activity without increased osteoblastic activity
Age related 3
rd
decade of life starts slow decline
in bone mass at rate of 0.5-1% per year
Most common types of fx: hip and radius
Female > Male
Secondary
Hypercortinism
Hypertiroidsm
Drugs induce



What is steroid ?
Steroid = group of organic compounds
Steroid hormones : Androgen, Estrogen
Corticosteroid : steroid hormones naturally produce in
adrenal cortex
Glucocorticoid (regulates metabolism aspect )+
Mineralocorticoid (maintain blood volume & renal
electrolytes)

Analog of corticosteroids are Synthesized (medical
drugs). Most medical steroid drugs are Glucocorticoid :
Group A : prednisolone, methylprednisolone, prednisone
Group B : triamcinolone, budesonide
Group C : dexamethasone
Group D : betamethasone


Introduction
Glucocorticoid (GC)-induced osteoporosis is the
most common cause of secondary osteoporosis
Bone loss may occur with or without other
manifestations and its severity is dependent on
both the dose and duration of GC treatment
CELLULAR AND MOLECULAR MECHANISMS OF
GCOP

GCs and osteoblast activity
Increase the apoptosis of osteoblasts and mature
osteocyte. Apoptosis may involve decreased
expression of the Bcl-2 gene and increased
expression of the Bax gene
Reduced osteoblast differentiation may be the result
of GC-induced repression of bone morphogenic
protein-2 (BMP-2) and expression of core binding
factor a1 (Cbfa1)
GCs suppress the synthesis of type I collagen and b-1
integrin (two major components of the matrix) and
increase the synthesis of collagenase 3 (or MMP-13;
a metalloproteinase which cleaves collagen fibrils),
inhibiting bone matrix formation by osteoblasts

GCs and osteoclast activity
the effects of GCs on osteoclasts are less known due
to the inherent difficulties of study
GCs cannot affect directly the bone-resorbing activity
of mature osteoclasts dont have receptor GC


CELLULAR AND MOLECULAR MECHANISMS OF
GCOP

GCs and local bone factors
Cytokines : Interleukin-1 (IL-1) and interleukin-6
(IL-6) induce bone resorption and inhibit bone
formation
Growth factors: Insulin-like growth factors (IGFs)
have an anabolic effect on bone cells that IGF-I
and IGF-II receptors. They increase the
replication of osteoblasts. Synthesis of IGF-I in
osteoblasts is decreased by GCs
CELLULAR AND MOLECULAR MECHANISMS OF
GCOP

EXTRASKELETAL ACTIONS OF
GLUCOCORTICOIDS

Effects on calcium homeostasis : Decrease
intestinal absorption of calcium and phosphate.
Increased renal excretion of calcium
PTH : GCs induce a negative calcium balance
that leads to secondary hyperparathyroidism.
Persistent elevated PTH can increase bone
resorption
Sex hormones : GCs reduce production. Pituitary
LH decreased Estrogen and testosteron
decreased


Pathogenesis
Overview of the mechanisms of glucocorticoid-induced osteoporosis (GCOP).
Osteoporosis results from an imbalance between osteoblast and osteoclast
activity. BMP-2: bone morphogenic protein-2; Cbfa1: core binding factor a1; Bcl-2:
B-cell leukemia/lymphoma-2 apoptosis regulator; Bax: BCL-2-associated X
protein; IGF-I: insulin-like growth factor-I; IGFBP: IGF binding protein; IGFBP-rPs:
IGFBP-related proteins; HGF: hepatocyte growth factor; RANKL: receptor
activator of the nuclear factor-B ligand ; CSF-1: colony-stimulating factor-1;
OPG: osteoprotegerin; PGE2: : Prostaglandin E 2; PGHS-2 prostaglandin
synthase-2
Pathogenesis Summary
GCs can influence bone remodeling in a number
of ways and at any stage of the remodeling cycle
But the primary mechanism is Decreased Bone
Formation
Decrease in bone formation :
Inhibition of osteoblast production of bone matrix
Induction of apoptosis of osteoblasts
Decrease in synthesis of insulin-like growth factor I
Transient increase in bone resorption
Promotion of osteoclastogenesis by increasing
RANKL and decreasing osteoprotegerin expression
in stromal and osteoblastic cells

Diagnosis of steroid-induce OP
Medical History and Clinical Evaluation
Laboratory tests and markers of bone turnover
Radiograph & Bone Mineral Density (BMD)
Assessment

Anamnesis & Medical history
Sex and Age
History of autoimmune disease, related with
steroid use
Calcium and alcohol intake, smoking, physical
activity
Menstrual/Fertility status
Back Pain, Myalgia
Clinical Evaluation
Systemic manifestation:
Moon face
Truncal obesity / Weight Gain
Muscle weakness (myopathy)
Skin problems
Psychological affects
Laboratory Test
CBC, marker of renal and liver function
Osteocalcin, Serum and 24-hr urine calcium
serum levels of 25-hydroxyvitamin D
Alkaline phosphatase
thyroid-stimulating hormone parathyroid hormone
Radiograph & BMD
Because trabecular bone and the cortical rim of
the vertebrae are lost more rapidly than cortical
bone from the long bone, the earliest changes
can be detected in the spine vertebrae and in
proximal femur using DXA
AP/Lat radiograph Spine vertebral
AP radiograph femur Singh Index
Wedging
vertebrae
Cod fish
Vertebral body
bone density
decreased
Singh Index
Grade VI : all trabecular visible
Grade V : principal tensile & principal compressive trabeculae is
accentuated
Grade IV : principal tensile trabeculae are markedly reduced but can
still be traced from lateral cortex to upper part of the femoral
neck
Grade III : break in principal tensile (definite osteoporosis)
Grade II : only principal compressive trabeculae stand out prominently
Grade I : principal compressive trabeculae are markedly reduced in number
and are no longer prominent

Types of BMD testing
Dual energy x-ray absorptiometry (DXA or DEXA).
Gold Standard
Measures BMD in spine, hip, or wrist
Completed in a few minutes
Radiation exposure less than 1/10 of standard x-ray
Ultrasound densitometry
Measures BMD in heel, patella
Cost-effective
Single-energy x-ray absorptiometry and peripheral
dual x-ray
Quantitative computed tomography (QCT)
Radiographic absorptiometry
BMD Assessment
Changes in BMD early on during GC therapy can be
detected by dual-energy X-ray absorptiometry (DXA),
classic X-ray studies are useful to detect vertebral
compression fractures

DEXA
Normal: T score above 1
Osteopenia: T score between 1 and 2.5
Osteoporosis: T score at or below 2.5
Severe osteoporosis: T score 2.5 or lower in the
presence of 1 or more fractures
Treatment
Aims to prevent and minimize bone loss and fracture,
to increase BMD and, at least partially, to reverse the
effects of GC

Vitamin D effect in osteoblast : stimulates synthesis of
osteocalcin and osteopontin help bone formation

Anyone receiving 7.5mg 15mg daily steroid for more
than 3 months should undergo prevention program.
Calcium and Vit D Replacement.(Adults) Ca 1500-
2000mg/day (unless contraindicated) & 400 IU of vit D
Child 400-700 mg/day
Adolescent 1000-1500 mg/day


Anti resorptive therapy : Bisphosphonates most
widely used
Bisphosphonates decrease the resorptive
activity of osteoclasts, increase osteoclast
apoptosis and decrease osteoblast and osteocyte
apoptosis
alendronate (5 and 10 mg/day or 70 mg/week)
and risedronate (5 mg/day or 35 mg/week)
Management algorithm for glucocorticoid osteoporosis.
Sambrook P N Ann Rheum Dis 2005;64:176-178
2005 by BMJ Publishing Group Ltd and European League Against Rheumatism
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