Secondary Osteoporosis Presentation

6/19/2016 1

Department of Clinical Biochemistry TUMS

21395/3/30

Outline

Introduction

Types of osteoporosis

Conclusion

3

Bone Remodeling

“Osteo”is Latin for “bone”

“Porosis” means “porous or full of holes”

“Osteoporosis” means “bones that are full of holes

What is osteoporosis?

4

Definition:

Osteoporosis

BMD

T- score

What is osteoporosis?

5BMD:Bone mineral density

Epidemiology

Estimated that more than 200 millions of individuals

suffer from osteoporosis worldwide.

In Iran

Year Osteoporosis

2010 3024798

2020 3592708

6

6/19/2016 7

Bone remodeling

9

Type of osteoporosis

Primary osteoporosis

Secondary 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


Presence of an underlying disease or medication

Secondary osteoporosis

11

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

12

Diabetes mellitus

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

13

Hepatic osteodystrophy

14

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.

15

16

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

OPG/RANK/RANKL

17Robbins basic pathology. Elsevier Health Sciences, 2012.

18

hepatic

osteodystrophy


factors

Adipokines

(IGF-1) deficiency


LCA:Lithocholic acid






LCA


GGT

(IGF-1) deficiency

19Insulin-like growth factor-I and bone. IBMS BoneKEy. 2011

20

hepatic

osteodystrophy


factors

Adipokines

(IGF-1) deficiency








LCA


GGT

Adipokines

Leptin and bone: A consensus emerging? IBMS BoneKEy. 2007

21

22

hepatic

osteodystrophy


factors

Adipokines

(IGF-1) deficiency








LCA


GGT

Important for

osteocalcin synthesis.

Antiapoptotic effect on

osteoblasts.

RANKL

Glucocorticoid-induced osteoporosis

(GIO)

23

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%.

24

25

Pathogenesis of bone loss in CS

Extraskeletal events Skeletal events

26

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)

27

Osteoporosis and diabetes

28AGEs: Advanced glycated end products

IGF-1

Diabetic

osteodystrophy

InsulinInsulin

resistance

IGF-1AGEs

Diabetic osteodystrophy

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30AGEs: Advanced glycation end products

IGF-1

Diabetic

osteodystrophy

InsulinInsulin

resistance

IGF-1AGEs

Gaucher disease and osteoporosis

31

Gluco-cerebrosidase

Ceramide Glucose

Gluco-cerebroside

Gaucher disease

32

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.

33

34

Bone diseases

in GD

Cathepsin K

Proinflammatory

cytokines Osteoblast

opoptosis

Osteoclastogenes

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

36

Bone Disease in Cystic Fibrosis

37

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

39

CFBD

Inflammatory

cytokines

Pathophysiology of CFBD

CFBD:CF-related bone disease

S1P: sphingosine-1-phosphate

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.

40

41

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

42

Bone remodeling

Multiple connections: new concepts in bone health. 2010

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Bone Formation

Bone Resorption

Conclusion

chronic liver diseases

Cushing syndrome

Gaucher disease Cystic fibrosis

Diabetes

Secondary Osteoporosis

Conclusion

44

OPG/RANK/RANKL

Questions or Comments?

45Will your bones as long as you do?

Tanks for your attention

Secondary Osteoporosis Presentation

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