secondary osteoporosis presentation
TRANSCRIPT
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6/19/2016 1
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Department of Clinical Biochemistry TUMS
21395/3/30
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Outline
Introduction
Types of osteoporosis
Conclusion
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Bone Remodeling
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“Osteo”is Latin for “bone”
“Porosis” means “porous or full of holes”
“Osteoporosis” means “bones that are full of holes
What is osteoporosis?
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Definition:
Osteoporosis
BMD
T- score
What is osteoporosis?
5BMD:Bone mineral density
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Epidemiology
Estimated that more than 200 millions of individuals
suffer from osteoporosis worldwide.
In Iran
Year Osteoporosis
2010 3024798
2020 3592708
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6/19/2016 7
Bone remodeling
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Type of osteoporosis
Primary osteoporosis
Secondary osteoporosis
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Types of osteoporosis
1. Postmenopausal osteoporosis (Type I)
2. Age-related (senile) osteoporosis (Type II(
1. Juvenile and adult idiopathic osteoporosis (JIO)
2. Pregnancy and lactation-associated osteoporosis
3. Localized osteoporosis10
Primary osteoporosis
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Types of osteoporosis
Presence of an underlying disease or medication
Secondary osteoporosis
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Disease induced osteoporosis
Gastrointestinal, nutritional and hepatic disorders
Celiac disease
Inflammatory bowel disease
Gastric surgery
Eating disorders
Chronic liver diseases
Endocrine or Metabolic Disease
Hypogonadism
Hypercalciuria
Hyperthyroidism
Hyperparathyroidism
Acromegaly
Growth hormone deficiency
Cushing’s syndrome
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Diabetes mellitus
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Hematological disorders Autoimmune disorders
Monoclonal gammopathy of
uncertain significance(MGUS)
Multiple myeloma
Systemic mastocytosis
Beta thalassemia major
Rheumatoid arthritis
Systemic lupus erythematosus
Multiple sclerosis
Disease induced osteoporosis
Other
Depression
Organ transplantation
Immobilization
Some cancers
Renal tubular acidosis
Gaucher’s diseas
Cystic fibrosis
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Hepatic osteodystrophy
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Hepatic osteodystrophy
Hepatic osteodystrophy comprises two types of change in the
bone:
- Osteoporosis
- Osteomalacia
A bone mass loss has been reported in 20-50% of
patients with chronic liver diseases.
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hepatic
osteodystrophy
OPG/RANK/RANKLGenetic
factors
Adipokines
(IGF-1) deficiency
RANK: Receptor Activator of Nuclear Factor κ B
LCA: Lithocholic acid
GGT: Gamma glutamyl transpeptidase
IGF-1: Insulin like growth factor 1
RANKL: Receptor activator of nuclear factor kappa-B ligand
OPG: Osteoprotegerin
Vitamin K deficiencyBilirubin
LCA
Pathophysiology of hepatic osteodystrophy
GGT
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OPG/RANK/RANKL
17Robbins basic pathology. Elsevier Health Sciences, 2012.
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hepatic
osteodystrophy
OPG/RANK/RANKLGenetic
factors
Adipokines
(IGF-1) deficiency
RANK: Receptor Activator of Nuclear Factor κ B
LCA:Lithocholic acid
GGT: Gamma glutamyl transpeptidase
IGF-1: Insulin like growth factor 1
RANKL: Receptor activator of nuclear factor kappa-B ligand
OPG: Osteoprotegerin
Vitamin K deficiencyBilirubin
LCA
Pathophysiology of hepatic osteodystrophy
GGT
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(IGF-1) deficiency
19Insulin-like growth factor-I and bone. IBMS BoneKEy. 2011
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hepatic
osteodystrophy
OPG/RANK/RANKLGenetic
factors
Adipokines
(IGF-1) deficiency
RANK: Receptor Activator of Nuclear Factor κ B
LCA:Lithocholic acid
GGT: Gamma glutamyl transpeptidase
IGF-1: Insulin like growth factor 1
RANKL: Receptor activator of nuclear factor kappa-B ligand
OPG: Osteoprotegerin
Vitamin K deficiencyBilirubin
LCA
Pathophysiology of hepatic osteodystrophy
GGT
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Adipokines
Leptin and bone: A consensus emerging? IBMS BoneKEy. 2007
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hepatic
osteodystrophy
OPG/RANK/RANKLGenetic
factors
Adipokines
(IGF-1) deficiency
RANK: Receptor Activator of Nuclear Factor κ B
LCA:Lithocholic acid
GGT: Gamma glutamyl transpeptidase
IGF-1: Insulin like growth factor 1
RANKL: Receptor activator of nuclear factor kappa-B ligand
OPG: Osteoprotegerin
Vitamin K deficiencyBilirubin
LCA
Pathophysiology of hepatic osteodystrophy
GGT
Important for
osteocalcin synthesis.
Antiapoptotic effect on
osteoblasts.
RANKL
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Glucocorticoid-induced osteoporosis
(GIO)
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Cushing syndrome (CS) encompasses a group of hormonal disorders
caused by prolonged and high exposure levels to Glucocorticoids.
(GIO)
The prevalence of osteoporosis among patients with CS using
currently accepted WHO guideline is usually estimated 30–65%.
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Pathogenesis of bone loss in CS
Extraskeletal events Skeletal events
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Differentiation
Proliferation
FunctionOsteoblasts
Cell cycle arrest
Apoptosis
Osteocytes
Apoptosis
Osteoclasts
Differentiation
Skeletal events
24"Glucocorticoids and bone: local effects and systemic implications." Trends
in Endocrinology & Metabolism (2014)
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Osteoporosis and diabetes
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28AGEs: Advanced glycated end products
IGF-1
Diabetic
osteodystrophy
InsulinInsulin
resistance
IGF-1AGEs
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Diabetic osteodystrophy
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30AGEs: Advanced glycation end products
IGF-1
Diabetic
osteodystrophy
InsulinInsulin
resistance
IGF-1AGEs
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Gaucher disease and osteoporosis
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Gluco-cerebrosidase
Ceramide Glucose
Gluco-cerebroside
Gaucher disease
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Bone involvement is described to occur in approximately 75%
of GD-1 patients.
Gaucher disease
Osteoporosis
Bone pathology remains the main problem for GD I patients.
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Bone diseases
in GD
Cathepsin K
Proinflammatory
cytokines Osteoblast
opoptosis
Osteoclastogenes
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Examining the impact of bone pathology on type I Gaucher disease
10.2217/CLP.13.78 © 2014 Future Medicine Ltd
Pathophysiology of bone diseases in GD
OP: Osteoclast precursor
sRANKL: Soluble RANKL
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Cathepsin K
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Bone Disease in Cystic Fibrosis
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Cystic fibrosis
Mutations within the gene encoding for the CFTR
The incidence of osteopenia and osteoporosis in CF
patients ranges from 34 to 79 %.
38CFTR: Cystic fibrosis transmembrane conductance regulator
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CFBD
Inflammatory
cytokines
Pathophysiology of CFBD
CFBD:CF-related bone disease
S1P: sphingosine-1-phosphate
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Inflammatory cytokines
In patients with CF Th17,
neutrophils ,… producing the
pro-inflammatory cytokine
IL-17A.
In CF elevated levels of
(TNF-α, IL-1β, IL-6, IL-8,…(
stimulatory and/or inhibitory
effects on the development and
activity of bone cells.
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CFBDInflammatory
cytokines
PGE2
S1P
Glucocorticoids
Pathophysiology of CFBD
CFBD:CF-related bone disease
S1P: sphingosine-1-phosphate
Vit D,K and Ca
insufficiency
PGE2: Prostaglandin E2
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Bone remodeling
Multiple connections: new concepts in bone health. 2010
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Bone Formation
Bone Resorption
Conclusion
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chronic liver diseases
Cushing syndrome
Gaucher disease Cystic fibrosis
Diabetes
Secondary Osteoporosis
Conclusion
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OPG/RANK/RANKL
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Questions or Comments?
45Will your bones as long as you do?
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Tanks for your attention