Medication-Related Osteonecrosis of the Jaws: Bisphosphonates, Denosumab, and New Agents

216 Pages·2015·13.24 MB·English

by  Sven Otto (eds.)

Sven Otto Editor
Medication-Related
Osteonecrosis
of the Jaws
Bisphosphonates,
Denosumab,
and New Agents
123
Medication-Related Osteonecrosis
of the Jaws

Sven Otto

Editor
Medication-Related
Osteonecrosis
of the Jaws
Bisphosphonates, Denosumab,
and New Agents
Editor
Sven Otto , MD, DMD, FEBOMFS
Department of Oral and
Maxillofacial Surgery
Ludwig-Maximilians-University
of Munich
Munich
Germany
ISBN 978-3-662-43732-2 ISBN 978-3-662-43733-9 (eBook)
DOI 10.1007/978-3-662-43733-9
Springer Heidelberg New York Dordrecht London
Library of Congress Control Number: 2014951352
© Springer-Verlag Berlin Heidelberg 2015
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Foreword
What began as a link between intravenous bisphosphonates in cancer patients
and osteonecrosis of the jaw has greatly expanded to a defi nitive causation
from two intravenous bisphosphonates as well as several oral bisphospho-
nates for osteoporosis patients and a RANK ligand inhibitor for either cancer
patients or osteoporosis patients. Furthermore, the route of administration for
the RANK ligand inhibitors is subcutaneous rather than intravenous or oral.
Adding to the complexity of jaw osteonecrosis are more rare reports from
drugs which inhibit the vascular endothelial growth factor and others which
inhibit certain tyrosine kinase receptors as their main mechanism of action.
The textbook M edication - Related Osteonecrosis of the Jaws :
Bisphosphonates , Denosumab , and New Agents by Sven Otto explores the
science, pharmacodynamics, diagnosis, and treatment options in a complete
and comprehensive manner. Each chapter contains extensive evidence-based
as well as experience-based data designed to help the reader fully understand
the nuances of this complex and interesting disease as well as how it can be
managed and many times resolved.
S ven Otto himself has been one of the pioneers and leaders internationally
that brought to clinicians a clearer understanding of this complex pathophysi-
ology. Together with the experience and expertise of each chapter author, this
text becomes a required read and one that serves as a reference that helps
everyone in the treatment of osteonecrosis of the jaw.
As a recognized disease entity in the published literature, osteonecrosis of
the jaw was unheard of prior to 2003. In just a few years, it has become a
condition seen in nearly every dental offi ce throughout the world. While this
book thoroughly prepares the reader related to the current drugs causing
osteonecrosis of the jaw, new targeted drugs are coming to the marketplace
with similar and profound effects on normal cellular functions. Only the
naïve would think we have seen the last of jaw osteonecrosis.
FL , USA Robert E. Marx , DDS
v

Contents
1 Pharmacological Aspects of Antiresorptive Drugs:
Bisphosphonates and Denosumab . . . . . . . . . . . . . . . . . . . . . . . 1
Reiner Bartl and Emmo von Tresckow
2 Bisphosphonate and Denosumab Therapy:
Fields of Application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Cornelia Then , Emmo von Tresckow , Reiner Bartl ,
and Fuat S. Oduncu
3 Risk Factors for Medication-Related
Osteonecrosis of the Jaw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Tae -Geon Kwon
4 Defi nition, Clinical Features and Staging
of Medication- Related Osteonecrosis of the Jaw . . . . . . . . . . . 43
Sven Otto , Tae-Geon Kwon , and Alexandre Th. Assaf
5 Epidemiology of Medication- Related
Osteonecrosis of the Jaw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Towy Sorel Lazarovici and Tal Yoffe
6 Imaging Modalities and Characteristics
in Medication-Related Osteonecrosis of the Jaw . . . . . . . . . . . 63
Florian A. Probst , Monika Probst ,
and Sotirios Bisdas
7 Treatment of Medication- Related
Osteonecrosis of the Jaw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Christoph Pautke
8 Local and Microvascular Free Flaps in Patients
with Medication-Related Osteonecrosis
of the Jaw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Thomas Mücke and David A. Mitchell
9 Adjuvant Treatment Options in the Management
of Medication-Related Osteonecrosis of the Jaw . . . . . . . . . . . 103
Paolo Vescovi , Maddalena Manfredi ,
and Elisabetta Merigo
vii
viii Contents
10 New and Innovative Treatment Strategies
for Medication-Related Osteonecrosis
of the Jaw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Riham M. Fliefel and Pit J. Voss
11 Microbiology and Antibiotics in the Context
of Medication-Related Osteonecrosis of the Jaw . . . . . . . . . . . 121
Sebastian Hoefert
12 Histopathology of Medication-Related
Osteonecrosis of the Jaw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Risa Chaisuparat and Bruno C. Jham
13 Pathogenesis of Medication- Related
Osteonecrosis of the Jaw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Sven Otto , Jose Ignacio Aguirre , Ezher Dayisoylu,
and Thomas Ziebart
14 Risk Reduction of Medication-Related
Osteonecrosis of the Jaw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Noam Yarom and Stefano Fedele
15 Animal Models of Medication-Related Osteonecrosis
of the Jaw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Matthew R. Allen
16 Dental Rehabilitation in Patients Receiving
Antiresorptive Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Sebastian Hoefert , Feraydoon Sharghi, and Eva Engel
17 Dental Implants in the Context Antiresorptive
Drugs and Medication-Related Osteonecrosis of the Jaw . . . . 179
Yorck Alexander Zebuhr
18 Osteonecrosis of the Jaw in Association
with Targeted Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Matthias Troeltzsch , Markus Troeltzsch , Christoph Pache,
and Timothy Woodlock
19 History of Osteonecrosis of the Jaw. . . . . . . . . . . . . . . . . . . . . . 201
Sebastian Hoefert , Claudia Sade Hoefert,
and Martin Widmann
20 Future Perspectives of Bisphosphonates in Maxillofacial,
Dental, and Medical Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Ralf Smeets, Henning Hanken, Ole Jung, and Max Heiland
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
1
Pharmacological Aspects
of Antiresorptive Drugs:
Bisphosphonates and Denosumab
Reiner Bartl and Emmo von Tresckow
Abstract
B isphosphonates and denosumab are the most widely used classes of anti-
resorptive osteotrop drugs worldwide. They are used to treat a variety of
bone disorders including osteoporosis, metastatic bone disease and hyper-
calcemia of malignancy. Bisphosphonates are administered either orally or
intravenously, while denosumab is injected subcutaneously. While bisphos-
phonates are not metabolized and have a strong affi nity to the bone and a
very long half-life in the bone (months–years), denosumab is an antibody
which is metabolized, not specifi cally stored, in the bone and has a short
half-l ife (weeks). Both substance classes have strong inhibitory effects
towards bone resorption and are therefore used for the treatment of osteopo-
rosis and metastatic bone disease as well as other bone disorders with great
success. Generally, bisphosphonates and denosumab are well tolerated and
have few side effects. However, both substance classes of osteotrop antire-
sorptives have one side effect in common, namely, osteonecrosis of the jaw.
utes to both. The macroscopic skeleton consists of
Introduction two major components: compact or cortical bone
and the cancellous or spongy bone [1 ] (Fig. 1 .1 ).
Bone fulfi ls two mechanical tasks: weight bearing Modeling is continuous during skeletal devel-
and fl exibility at the lowest possible weight. This is opment, then it is greatly reduced and ceases
accomplished by the combination of an elastic completely after skeletal maturity, while remod-
matrix for fl exibility hardened by the deposition of eling takes place throughout life. Modeling
calcium and phosphate which gives bone its rigid- results in changes in the shape and size of the
ity, while the highly developed architecture contrib- bone, while remodeling maintains but usually
does not change size and shape. It is carried out
by two major bone cells: the osteoclasts which
R. Bartl
resorb the bone and the osteoblasts which form
Ehrenfelsstrasse 5, 81375 Munich, Germany
e-mail: [email protected] the bone [1 ] . Characteristic of active osteoclasts
are their “ruffl ed borders” which lie directly on
E. von Tresckow (*)
the surface of the bone. Howship’s lacunae are
Rosenstrasse 2, 82319 Starnberg, Germany
e-mail: [email protected] formed as the osteoclasts carve out the bone [1 ].
S. Otto (ed.), Medication-Related Osteonecrosis of the Jaws: Bisphosphonates, Denosumab, and New Agents, 1
DOI 10.1007/978-3-662-43733-9_1, © Springer-Verlag Berlin Heidelberg 2015