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Osteoporosis International
Published in: Osteoporosis International 11/2011

01-11-2011 | Original Article

Bone and bone marrow pro-osteoclastogenic cytokines are up-regulated in osteoporosis fragility fractures

Authors: P. D’Amelio, I. Roato, L. D’Amico, L. Veneziano, E. Suman, F. Sassi, G. Bisignano, R. Ferracini, G. Gargiulo, F. Castoldi, G. P. Pescarmona, G. C. Isaia

Published in: Osteoporosis International | Issue 11/2011

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Abstract

Summary

This study evaluates cytokines production in bone and bone marrow of patients with an osteoporotic fracture or with osteoarthritis by real time PCR, Western blot and immunohistochemistry. We demonstrate that the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in patients with osteoporotic fractures.

Introduction

Fragility fractures are the resultant of low bone mass and poor bone architecture typical of osteoporosis. Cytokines involved in the control of bone cell maturation and function are produced by both bone itself and bone marrow cells, but the roles of these two sources in its control and the amounts they produce are not clear. This study compares their production in patients with an osteoporotic fracture and those with osteoarthritis.

Methods

We evaluated 52 femoral heads from women subjected to hip-joint replacement surgery for femoral neck fractures due to low-energy trauma (37), or for osteoarthritis (15). Total RNA was extracted from both bone and bone marrow, and quantitative PCR was used to identify the receptor activator of nuclear factor kB Ligand (RANKL), osteoprotegerin (OPG), macrophage colony stimulating factor (M-CSF), transforming growth factor β (TGFβ), Dickoppf-1 (DKK-1) and sclerostin (SOST) expression. Immunohistochemistry and Western blot were performed in order to quantify and localize in bone and bone marrow the cytokines.

Results

We found an increase of RANKL/OPG ratio, M-CSF, SOST and DKK-1 in fractured patients, whereas TGFβ was increased in osteoarthritic bone. Bone marrow produced greater amounts of RANKL, M-CSF and TGFβ compared to bone, whereas the production of DKK-1 and SOST was higher in bone.

Conclusions

We show that bone marrow cells produced the greater amount of pro-osteoclastogenic cytokines, whereas bone cells produced higher amount of osteoblast inhibitors in patients with fragility fracture, thus the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in these patients.
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Metadata
Title
Bone and bone marrow pro-osteoclastogenic cytokines are up-regulated in osteoporosis fragility fractures
Authors
P. D’Amelio
I. Roato
L. D’Amico
L. Veneziano
E. Suman
F. Sassi
G. Bisignano
R. Ferracini
G. Gargiulo
F. Castoldi
G. P. Pescarmona
G. C. Isaia
Publication date
01-11-2011
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 11/2011
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-010-1496-7

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