2. The role of estrogen in osteoporosis
Advisor: D.r mohiti
By: zahra malekpour
Dep of biochemistry
1394

3. Introduction Osteoporosis: A metabolic bone disorder
low bone mass and increase in bone fragility
Bone mass is a determinant of bone strength.
bone formation peak is at the end of growth.
Sex hormones as estrogen have important role in pubertal skeleton growth.
Estrogen is a regulator bone metabolism.

4. Bone Formation Bone compounds include: Ossification (osteogenesis):
support cells: osteoblasts and osteocytes
remodeling cells: osteoclasts
non-mineral matrix: collagen & proteins called osteoid
Ossification (osteogenesis):
Synthesis of extracellular organic matrix (osteoid)
Matrix mineralization leading to bone formation .
Remodeling of bone by the process of resorption and reformation

5. Bone remodeling
The process of osteoclasts resorb bone and osteoblasts form new bone.
Importance of bone remodeling:
Bone enabling to respond and adapt to load induced strain.
replace old or damaged bone tissue.
maintenance calcium homeostasis.

6. Bone remodeling Bone remodeling unit: Bone resorption: Bone formation:
Activation of osteoclasts
Resorption of minerals and matrix
Bone formation:
Migration and differentiation of preosteoblast
Matrix formation
mineralization

7. Bone remodeling

8. The bone resorption process

9. The bone resorption process

10. The bone formation process

11. The bone formation process

12. The Role of estrogen In
Bone remodeling

13. Estrogen Are as ovarian sex hormones.
Responsible for cellular proliferation and growth of tissues related to reproduction.
In premenopausal women ovaries are the most important source of circulating estrogens.
Placenta also secrets estrogens.
In postmenopausal women and men extragonadal tissues are the source of estrogen.

14. Estrogen effects on osteocytes/osteoclasts/osteoblasts
regulator of bone growth
regulation of bone remodeling
Decrease bone resorption
maintenance of bone formation
regulation of osteoclasts

15. Estrogen receptors Classic receptors: Non classic receptors
Erα: gen in chromosome 6, protein 595 aa
Erβ: gen in chromosome 14, protein 530 aa
Non classic receptors
G protein-coupled estrogen receptor 1(GPER1) or (GPR30):
Gen in chromosome 7, protein 375 aa
present in various cell membrane elements
respons for rapid estrogen signaling

16. Isoforms of Erα & Erβ

17. Estrogen signaling pathway

18. The role of estrogen in bone remodeling

19. The role of estrogen on T cells

21. The role of estrogen in bone remodeling

22. Health bone & osteoporosis

23. Bone formation and age

24. Treatment Bisphosphonates: Antiresorptive medications:
nonhydrolyzable analogues of PPi
bind divalent metal ions, such as Ca2+
rapidly cleared from the circulation and bind to areas undergoing osteoclastic resorption
The non-nitrogen containing bisphosphonates: are metabolized in osteoclasts to analogs of ATP, induce apoptose. (clodronate, etidronate)
Nitrogen-Containing Bisphosphonates: Inhibit Farnesyl Diphosphate Synthase, Prevents the Prenylation (alendronate, ibandronate, zolendronate)

25. Treatment 2. Denosumab 3. selective estrogen receptor modulators(SERM)
Human monoclonal antibody
Against RANKL
3. selective estrogen receptor modulators(SERM)
(Act as agonist/antagonist of estrogen)
chemical structure
relative level of corepressors and coactivators
type of ER-dependent regulatory sequences; ERE or other transcription factor binding sites.
ERα/ERβ ratio varies between tissues

26. Sites of action of different classes of drug

27. Reference
Khosla S, Jo Oursler M, G. Monroe D. Estrogen and the skeleton. Trends in Endocrinology and Metabolism. 2012; 23(11):
Weitzmann M.N, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. J. Clin. Invest. 2006; 116:1186–1194.
Vrtacniv P, Ostanek B, Mencej-Bedrac S, Marc J. The many faces of estrogen signaling . Biochemia Medica 2014; 24(3):329–42.
Cui J, Shen Y, and Li R.Estrogen synthesis and signaling pathways during aging: from periphery to brain. Trends in Molecular Medicine. 2013; 19(3):
Manolagas S.C, Obrien CH.A. and Almeida M. The role of estrogen and androgen receptors in bone health and disease. Nat. Rev. Endocrinol ; 9: 699–712.

28. Reference
Singh D, Sanyal s, and Chattopadhyay N. The role of estrogen in bone growth and formation: changes at puberty. Cell Health and Cytoskeleton. 2011; 3:1–12
Galea G, Price J, Lanyon L. Estrogen receptors’ roles in the control of mechanically adaptive bone (re)modeling. Nature(BoneKEy Reports 2). 2013; 413:1-7.
Roelofs AJ, Thompson k, Gordon SH, et al. Molecular Mechanisms of Action of Bisphosphonates: Current Status. Clin Cancer Res. 2006;12:6222s-6230s.
Das S and Crockett JC. Osteoporosis – a current view of pharmacological prevention and treatment. Drug Design, Development and Therapy. 2013; 7:435–448

29. thanks