Neue Targets in der Osteoporosetherapie 12 New Targets in Osteoporosis Therapy F. Jakob, L. Seefried, P. M. Jehle

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3 Neue Targets in der Osteoporosetherapie 12 New Targets in Osteoporosis Therapy F. Jakob, L. Seefried, P. M. Jehle Solche Daten zeigen, dass die Interfaces, die der Knochen zu anderen Organsystemen aufweist, sei es das Immunsystem, die Muskulatur oder der Stoffwechsel, bislang erheblich unterschätzt wurden und dass hier hochinteressante Entwicklungen möglich sind, die über den Knochen alleine hinausgehen.

4 Science 3 June 2005 Vol no. 5727, pp

5 Science 3 June 2005 Vol no. 5727, pp

6 Science 3 June 2005 Vol no. 5727, pp

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9 mammopoesis Ca RANK Ligand

10 resorption of bone synthesis of bone osteoclast steady state osteoblast IL6 IL6 IL6 IL1 E2 IL6 P IL6 menstruation ovulation menstruation

11 PV1 M-CSF rankl c-fos NF B V 2 TRAF6 CSr6 cathepsin k carbone anhydrase II H + -ATPase determination proliferation differentation polarisation resorption

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13 The breast and the skeleton communicate during lactation to provide a steady supply of calcium for milk production. Wysolmerski J J JCEM 2012;97: by Endocrine Society

14 PTHrP IL6 Wachstumsfaktoren Ca NFkB Osteoklasten GM- CSF

15 Lancet, 360, 2061 Fornarina Fornarina

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23 Bone and the epidermo-pilosebaceous unit of the skin share a lifelong renewal activity where similar molecular players operate, and because mammary glands and hair follicles are both skin appendages

24 Das Progesteron bereitet den weiblichen Körper auf die Fortpflanzung vor

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27 Antirheumatika 65+ J. 29% Alterstruktur Männer (22 Mio. Verordnungen) unter 30 J. 12% J. 14% 65+ J. 45% Alterstruktur Frauen (32 Mio. Verordnungen) unter 30 J. 9% J. 9% J. 21% J. 24% J. 18% J. 19% 50% 37% bis 54 ab 54 bis 54 50% ab 54 63% Quelle: IMS Health, VIP

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31 Factors mediating luteal ce ll apoptosis in humans. The Fas and Fas-ligand and Bcl-2 and Bax systems are involved in the intracellu lar signaling pathway for apoptosis, and apoptosis is induced by caspase-3 activation. Cytokines may also be involved in apoptosis. HCG works as a survival factor by regulating apoptosis-related factors, such as Fas, the Bcl-2 and Bax syst em and survivin

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42 9 MAY VO L N AT U R E 2 1 1

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44 Adipozyt Leptin Osteocalcin Adiponectin Osteoblast Osteocalcin -Zellen Insulin Adiponectin Pankreas Cell 130, 456

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48 Osteocalcin, a bone-derived multifunctional hormone. Undercarboxylated osteocalcin stimulates insulin secretion and β-cell proliferation in the pancreas, energy expenditure by muscle, and insulin sensitivity in adipose tissue, muscle and liver. In addition, it promotes male fertility by stimulating testosterone synthesis in Leydig cells of the testis through the activation of its receptor, GPRC6A, in these cells.

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59 Der zum Diabetes neigende Stoffwechsel und die Überproduktion an Androgenen verringern die Energieverluste durch Wärme und sorgen für den Aufbau von Fettdepots. Insulin trägt zusammen mit dem Hormon Leptin, das Appetit und Fettmasse reguliert, zum Erhalt von Energiebalance und der Funktion der Eierstöcke be Leider wendet sich dieser evolutionsbiologisch angelegte Vorteil in Zeiten hochkalorischer Nahrungszufuhr ins Gegenteil

60 Our results show for the first time that female O/PCOS-prone rats gain a survival advantage over their lean-prone congenics when confronted with a challenge of time-limited feeding and an opportunity for food-related activity The longer survival of female O/PCOS-prone rats compared with their leanprone congenics relates to higher baseline energy reserves, greater When leptin signaling is defective, as in the O/PCOS-prone rats, the energy homeostasis pathway involving feeding-related peptides, such as neuropeptide Y, is impaired. This impairment results in increased appetite, decreased energy expenditure, and greater fat accumulation effects that are advantageous for survival in the AAC

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64 Leider wendet sich dieser evolutionsbiologisch angelegte Vorteil in Zeiten hochkalorischer Nahrungszufuhr ins Gegenteil

65 MESENCHYMAL STEM CELLS MYOBLAST CHONDROCYT OSTEOBLAST ADIPOCYTE

66 24 OCTOBER 2008 VOL 322 SCIENCE

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