This document discusses various types of secondary osteoporosis, including those caused by chronic liver diseases, Cushing syndrome, Gaucher disease, cystic fibrosis, and diabetes. It provides details on the pathophysiology and mechanisms by which these conditions can lead to osteoporosis, such as through imbalances in the OPG/RANK/RANKL pathway, deficiencies in IGF-1 or vitamin K, elevated inflammatory cytokines, and effects on osteoblast and osteoclast activity. The document also covers topics like bone remodeling and epidemiology of osteoporosis.

1. 6/19/2016 1

2. Department of Clinical Biochemistry
TUMS
21395/3/30

3. Outline
Introduction
Types of osteoporosis
Conclusion
3
Bone Remodeling

4. “Osteo”is Latin for “bone”
“Porosis” means “porous or full of holes”
“Osteoporosis” means “bones that are full of holes
What is osteoporosis?
4

5. Definition:
Osteoporosis
BMD
T- score
What is osteoporosis?
5
BMD:Bone mineral density

6. Epidemiology
Estimated that more than 200 millions of individuals
suffer from osteoporosis worldwide.
In Iran
Year Osteoporosis
2010 3024798
2020 3592708
6

7. 6/19/2016 7
Bone remodeling

8. 8

9. 9
Type of osteoporosis
Primary
osteoporosis
Secondary
osteoporosis

10. 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 osteoporosis
10
Primary osteoporosis

11. Types of osteoporosis
 Presence of an underlying disease or medication
 Secondary osteoporosis
11

12. 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

13. 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

14. Hepatic osteodystrophy
14

15. 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. 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

17. OPG/RANK/RANKL
17Robbins basic pathology. Elsevier Health Sciences, 2012.

18. 18
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

19. (IGF-1) deficiency
19Insulin-like growth factor-I and bone. IBMS BoneKEy. 2011

20. 20
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

21. Adipokines
Leptin and bone: A consensus emerging? IBMS BoneKEy. 2007
21

22. 22
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

23. Glucocorticoid-induced osteoporosis
(GIO)
23

24. 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. 25
Pathogenesis of bone loss in CS
Extraskeletal events Skeletal events

26. 26
Differentiation
Proliferation
Function
Osteoblasts
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. 27
Osteoporosis and diabetes

28. 28AGEs: Advanced glycated end products
IGF-1
Diabetic
osteodystrophy
Insulin
Insulin
resistance
IGF-1AGEs

29. Diabetic osteodystrophy
29

30. 30AGEs: Advanced glycation end products
IGF-1
Diabetic
osteodystrophy
Insulin
Insulin
resistance
IGF-1AGEs

31. Gaucher disease and osteoporosis
31

32. Gluco-cerebrosidase
Ceramide Glucose
Gluco-cerebroside
Gaucher disease
32

33. 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. 34
Bone diseases
in GD
Cathepsin K
Proinflammatory
cytokines
Osteoblast
opoptosis
Osteoclastogenes

35. 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
35

36. Cathepsin K
36

37. Bone Disease in Cystic Fibrosis
37

38. Cystic fibrosis
Mutations within the gene encoding for the CFTR
The incidence of osteopenia and osteoporosis in CF
patients ranges from 34 to 79 %.
38
CFTR: Cystic fibrosis transmembrane conductance regulator

39. 39
CFBD
Inflammatory
cytokines
Pathophysiology of CFBD
CFBD:CF-related bone disease
S1P: sphingosine-1-phosphate

40. 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. 41
CFBD
Inflammatory
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. 42
Bone remodeling
Multiple connections: new concepts in bone health. 2010

43. 43
Bone Formation
Bone Resorption
Conclusion

44. chronic liver diseases
Cushing syndrome
Gaucher disease
Cystic fibrosis
Diabetes
Secondary Osteoporosis
Conclusion
44
OPG/RANK/RANKL

45. Questions or
Comments?
45Will your bones as long as you do?

46. Tanks for your attention