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Pathophysiologie des Knochenstoffwechsels

Pathophysiology of bone metabolism

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Zusammenfassung

Osteoporose ist eine multifaktorielle Erkrankung mit einem hohen Risiko für Fragilitätsfrakturen. Die Suszeptibilität ist durch Vererbung, Lebensweise und bestehende Krankheiten determiniert. Knochen wird von Osteoklasten, Osteoblasten und Osteozyten unter Vermittlung lokaler und systemischer Faktoren regeneriert. Insulinähnliche Wachstumsfaktoren, Bone Morphogenetic Proteins und wnt-Proteine sind anabol wirksam. Das RANK/RANK-Ligand- und Osteoprotegerin- (OPG-) System reguliert den Knochenabbau. So wird der Quotient aus OPG und dem osteoklastenstimulierenden RANKL günstig durch Sexualhormone, Vitamin D, Parathormon, Wachstumsfaktoren und mechanische Kräfte beeinflusst. Osteozyten regeln die Knochenmasse über Sclerostin, einen Inhibitor der Knochenbildung. Über Nebenschilddrüsen, Intestinum, Leber und Niere unterliegt die Knochensubstanz einer interaktiven Regulation durch den Kalzium-, Phosphat- und Vitamin-D-Stoffwechsel. Sexualhormone spielen eine wichtige Rolle für den Knochenaufbau in der Adoleszenz und den Verlust in der Menopause/Andropause. Überaktivität von Osteoklasten und/oder funktionelle Defizite von Osteoblasten/Osteozyten können den Knochenverlust und damit die Osteoporose fördern.

Abstract

Osteoporosis is a multifactorial disease entailing a high risk to sustain fragility fractures. Its susceptibility is determined by genetic and environmental factors and underlying diseases. Bone is rebuilt and regenerated by osteoclasts, osteoblasts and osteocytes. Local and systemic growth and differentiation factors such as Insulin-like growth factors, bone morphogenetic proteins and wnt-proteins confer anabolic signals, while the RANK/RANK-Ligand and Osteoprotegerin (OPG) system regulates bone resorption. The ratio of osteoclast stimulating RANKL and its soluble decoy receptor OPG is modulated by sex hormones, vitamin D, parathyroid hormone, local growth factors and mechanical loading. Osteocytes regulate bone mass via the bone formation inhibitor sclerostin. Bone is tightly interconnected with and regulated by the calcium/phosphate/vitamin D system via the parathyroid gland, the gut, liver and kidneys. Sex hormones are important for bone formation during adolescence and their loss in menopause/andropause exaggerates bone resorption. Basically over-activity of osteoclasts and/or functional deficits of osteoblasts can cause negative bone balance and favor osteoporosis.

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Abbreviations

BMP:

Bone Morphogenetic Proteins

CSR:

Kalzium-Sensing-Rezeptoren

DKK:

Dickkopf-Protein, Hemmstoff des wnt-Signalwegs

ECM:

Extrazelluläre Matrix

FGF-23:

Fibroblast Growth Factor 23

frz:

Frizzled-Rezeptor

LRP5:

Lipoprotein-related Protein 5, Ko-Rezeptor für frz

MSC:

Mesenchymale Stammzellen

OPG:

Osteoprotegerin

PPAR-γ:

Peroxisome Proliferator-Activated Receptor γ

PTH:

Parathormon

PTHrP:

Parathormon-related Peptide

RANK:

Receptor Activator of NF-κB

RANKL:

Receptor Activator of NF-κB Ligand

sFRP:

Secreted Frizzled Related Proteins, lösliche Rezeptoren für wnt

Wnt:

wnt-Proteine, Liganden für frz und sFRP

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehung/en hin: Ich halte Vorträge für die Firmen Servier, Novartis, Lilly, P&G.

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Authors and Affiliations

  1. Orthopädisches Zentrum für Muskuloskelettale Forschung, Universität Würzburg, Brettreichstraße 11, 97074, Würzburg, Deutschland

    F. Jakob, L. Seefried & R. Ebert

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  1. F. Jakob
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  2. L. Seefried
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  3. R. Ebert
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Correspondence to F. Jakob.

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Jakob, F., Seefried, L. & Ebert, R. Pathophysiologie des Knochenstoffwechsels. Internist 49, 1159–1169 (2008). https://doi.org/10.1007/s00108-008-2113-0

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