Table Of ContentJOINT DISEASE IN THE HORSE
SECOND EDITION
Edited by
C. Wayne McIlwraith, BVSc, PhD, Dr med vet Christopher E. Kawcak, DVM, PhD, Diplomate
(h.c. Vienna), DSc (Purdue), DSc (h.c. Massey), ACVS & ACVSMR
Laurea Dr (h.c. Turin), D vet med (h.c. London), Professor
FRCVS, Diplomate ACVS, ECVS, & ACVSMR Iron Rose Ranch University Chair in
University Distinguished Professor Musculoskeletal Research
Barbara Cox Anthony University Chair in Gail Holmes Equine Orthopaedic Research Center
Orthopaedics College of Veterinary Medicine and Biomedical
Director Orthopaedic Research Center Sciences
Gail Holmes Equine Orthopaedic Research Center School of Biomedical Engineering
College of Veterinary Medicine and Biomedical Director of Equine Clinical Services
Sciences Colorado State University
School of Biomedical Engineering Fort Collins, Colorado
Colorado State University
P. René van Weeren, DVM, PhD, Diplomate ECVS
Fort Collins, Colorado
Professor of Equine Musculoskeletal Biology
David D. Frisbie, DVM, PhD, Diplomate ACVS & Department of Equine Sciences
ACVSMR Faculty of Veterinary Medicine
Professor Utrecht University
Gail Holmes Equine Orthopaedic Research Center Utrecht, The Netherlands
College of Veterinary Medicine and Biomedical
Sciences
School of Biomedical Engineering
Colorado State University
Fort Collins, Colorado
3251 Riverport Lane
St. Louis, Missouri 63043
JOINT DISEASE IN THE HORSE, SECOND EDITION ISBN: 978-1-4557-5969-9
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Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden
our understanding, changes in research methods, professional practices, or medical treatment may become
necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds, or experiments described herein. In using such information or
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have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most
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Previous edition copyrighted 1996.
Library of Congress Cataloging-in-Publication Data
Joint disease in the horse / edited by C. Wayne McIlwraith, David D. Frisbie, Christopher E. Kawcak, P. René van Weeren. -- Second edition.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4557-5969-9 (hardcover : alk. paper)
I. McIlwraith, C. Wayne, editor. II. Frisbie, David D., editor. III. Kawcak, Christopher E., editor. IV. van Weeren, P. René 1957- , editor.
[DNLM: 1. Horse Diseases. 2. Joint Diseases--veterinary. SF 959.J64]
SF959.J64J385 2016
636.1’089672--dc23
2015015062
Vice President and Publisher: Loren Wilson
Content Strategy Director: Penny Rudolph
Content Development Manager: Jolynn Gower
Content Development Specialist: Brandi Graham
Publishing Services Manager: Jeffrey Patterson
Project Manager: Bill Drone
Designer: Brian Salisbury
Printed in China.
Last digit is the print number: 9 8 7 6 5 4 3 2 1
To Nancy, Myra, Erin, and Madelon for their continued participation in
what we do, as well as their support and patience,
AND to the horse, whose unselfish efforts and willingness to serve have
inspired much of the basic and clinical research reported in this text.
C O N T R I B U T O R S
Myra F. Barrett, DVM, MS, Diplomate ACVR Christopher E. Kawcak, DVM, PhD, Diplomate ACVS &
Assistant Professor of Diagnostic Imaging ACVSMR
Gail Holmes Equine Orthopaedic Research Center Professor
College of Veterinary Medicine and Biomedical Sciences Iron Rose Ranch University Chair in Musculoskeletal Research
Environmental and Radiological Health Sciences Gail Holmes Equine Orthopaedic Research Center
Colorado State University College of Veterinary Medicine and Biomedical Sciences
Fort Collins, Colorado School of Biomedical Engineering
Director of Equine Clinical Services
Pieter A. J. Brama, DVM, MBA, PhD, Diplomate ECVS Colorado State University
Professor of Veterinary Surgery Fort Collins, Colorado
School of Veterinary Medicine
Veterinary Science Centre Melissa R. King, DVM, PhD, Diplomate ACVSMR
University College Dublin Assistant Professor
Belfield, Dublin, Ireland Equine Sports Medicine and Rehabilitation
Gail Holmes Equine Orthopaedic Research Center
Janny C. de Grauw, DVM, PhD College of Veterinary Medicine and Biomedical Sciences
Resident in Veterinary Anesthesiology School of Biomedical Engineering
Faculty of Veterinary Medicine Colorado State University
Department of Equine Sciences Fort Collins, Colorado
Utrecht University
Utrecht, The Netherlands C. Wayne McIlwraith, BVSc, PhD, Dr med vet
(h.c. Vienna), DSc (Purdue), DSc (h.c. Massey),
David D. Frisbie, DVM, PhD, Diplomate ACVS & ACVSMR Laurea Dr (h.c. Turin), D vet med (h.c. London),
Professor FRCVS, Diplomate ACVS, ECVS, & ACVSMR
Gail Holmes Equine Orthopaedic Research Center University Distinguished Professor
College of Veterinary Medicine and Biomedical Sciences Barbara Cox Anthony University Chair in Orthopaedics
School of Biomedical Engineering Director Orthopaedic Research Center
Colorado State University Gail Holmes Equine Orthopaedic Research Center
Fort Collins, Colorado College of Veterinary Medicine and Biomedical Sciences
School of Biomedical Engineering
Laurie R. Goodrich, DVM, PhD, Diplomate ACVS Colorado State University
Associate Professor in Equine Surgery and Lameness Fort Collins, Colorado
Gail Holmes Equine Orthopaedic Research Center
College of Veterinary Medicine and Biomedical Sciences Kurt Selberg, MS, DVM, MS, Diplomate ACVR
School of Biomedical Engineering Assistant Professor
Colorado State University Department of Veterinary Biosciences and Diagnostic
Fort Collins, Colorado Imaging
College of Veterinary Medicine
Kevin K. Haussler, DVM, DC, PhD, Diplomate ACVSMR University of Georgia
Associate Professor Athens, Georgia
Gail Holmes Equine Orthopaedic Research Center
College of Veterinary Medicine and Biomedical Sciences
School of Biomedical Engineering
Colorado State University
Fort Collins, Colorado
vii
viii CONTRIBUTORS
P. René van Weeren, DVM, PhD, Diplomate ECVS Natasha M. Werpy, DVM, Diplomate ACVR
Professor of Equine Musculoskeletal Biology Associate Professor
Department of Equine Sciences Department of Large Animal Clinical Sciences
Faculty of Veterinary Medicine College of Veterinary Medicine
Utrecht University University of Florida
Utrecht, The Netherlands Gainesville, Florida
P R E FA C E T O T H E F I R S T E D I T I O N
Lameness is the most important cause of wastage in rac- It is the first time a book has been devoted to the subject of
ing horses as well as in horses that perform in other athletic joint disease in the horse, and the amount of new information
events. Joint injury and joint disease are the most common is impressive. With this book, we hope that clinicians now
causes of lameness, and together they represent a major part have a reference base with supportive data to provide more
of the caseload for equine clinicians. Many medical and sur- realistic answers to their clients and that the person involved
gical treatments exist for various joint problems, but many in research becomes more aware of what work has been com-
of these treatments are controversial, particularly with regard pleted to date.
to treatment selection and definitive treatment results. In Three issues of semantics require mention. For consis-
recent years, much progress has been made in basic research tency, we have chosen to use the word osteoarthritis instead
in inflammatory and degenerative joint problems in the of degenerative joint disease, which was previously used by
horse. In addition, prospective and retrospective studies have the editors and others as a synonym for osteoarthritis. Osteo-
resulted in more realistic figures for the prognosis and treat- arthritis is the preferred term today in the nonequine litera-
ment of many clinical entities. Much of the basic work in joint ture and has been adopted in this text. With our international
disease was originally done in laboratory animals, but more authorship, as second issue is the use of the term “infectious”
recently, considerable original work has been reported in the versus “infective.” As a British author has pointed out to us,
horse and in vitro work with equine tissue. infectious is frequently defined as “capable of being spread
The purpose of this book is to define the current status of from one host to another with or without direct contact,”
the rapidly changing area of developmental and degenerative thus, the equine influenza virus or equine herpesvirus could
joint disease, which is of significant clinical importance to the be regarded as an infectious organism. However, “infective”
horse. We have been fortunate to obtain contributors who by usage is more restricted in its definition, and Churchill’s
have done much of the original work. The principal objec- Medical Dictionary suggests “capable of causing infection” as
tives of this book are to present current scientific information its only definition. Therefore, it is felt that in the case of infec-
on the basic joint pathobiology and translate it into practical, tive arthritis, bacteria could not be regarded as infectious as
clinical usage for the equine clinician. At times, this can be in the case of respiratory viruses, although the bacteria could
difficult, and in some instances, only anecdotal information be regarded as infective because it is capable of causing infec-
is available. The contents are designed to be of value to both tion. The editors and scrutineers are concerned about this
researchers and clinicians. distinction in Britain; whereas in American literature vari-
Section I covers general principles in joint pathobiology ous terms (including septic) have been used synonymously.
and consists of eight chapters, written by contributors who Both terms are used in this text according to the contributor’s
have done original research in their areas. This section pro- preference. Hyaluronic acid, sodium hyaluronate, and hyal-
vides the necessary background information to effectively uronan are also used interchangeably. It has been suggested
evaluate and interpret the diagnostic and surgical aspects of that when the cation of polysaccharide is undetermined, the
the diseases covered later. Section II presents the pathology, compound is properly referred to as hyaluronan; therefore,
pathogenesis, and clinical diagnosis of traumatic and degen- this term is used.
erative joint disease. Section III discusses the treatments We would like to recognize the editorial and production
available for traumatic arthritis and osteoarthritis, includ- staffs of the W.B. Saunders Company for their professional
ing physical therapy, nonsteroidal antiinflammatory drugs, efforts on this project. We want to thank the authors for
intraarticular corticosteroids, hyaluronan, polysulfated gly- their excellent contributions, and Helen Mawhiney for sec-
cosaminoglycan, other chondroprotective drugs, and surgery. retarial assistance. We would also like to acknowledge Tom
In Section IV, osteochondritis dissecans, subchondral cystic McCracken, Phil Guzzy, and Conery Calhoun of Biograph-
lesions, infective arthritis, and other entities affecting joints ics; and Jenger Smith and Charley Kerlee of CSU Multi-Media
are presented. Section V includes current research relative to Instructional Development for their help with illustrations.
equine joint disease that has not been presented previously. Dr. McIlwraith gratefully acknowledges Drs. John F. Fessler
This includes the use of experimental models in the investi- and David C. Van Sickle for their early influence and mentor-
gation of equine arthritis, chondrocyte culturing and explant ing in starting a career in investigating equine joint disease.
culture systems, cellular responses and receptor mechanisms Finally, because many joint-associated (or orthopedic)
associated with bacterial lipopolysaccharide-induced joint problems remain to be solved for our equine patients, all roy-
damage, and finally, a summary by Dr. A. Robin Poole on the alties from this text will be used for ongoing research in our
future direction of arthritis research. Equine Orthopedic Research Laboratory at Colorado State
In the time since the W.B. Saunders Company approached University.
one of us (CWM) to write a book on equine joint disease,
C. Wayne McIlwraith
considerable new work has been undertaken and, fortunately,
much of this is captured in timely fashion by the contributors. Gayle W. Trotter
ix
P R E FA C E T O T H E S E C O N D E D I T I O N
As discussed in the preface to the first edition of this book, future directions in joint disease that will continue to improve
lameness is the most important cause of wastage in rac- our ability to treat horses are featured.
ing horses as well as in horses that perform in other athletic
events. Joint injury and joint disease are the most common ACKNOWLEDGMENTS
causes of lameness, and together they represent most of the
caseload for equine clinicians. Many medical and surgical Much of the book has been written by the four of us, but we have
treatments exist for various joint problems, and there have had particularly critical contributions from Dr. Myra Barrett in
been many advances in this area since 1996 as well as much both content and organization with the imaging parts of Chapter
clarification of the value of various treatments with evidence- 9 as well as Chapters 20 through 26. Drs. Natasha Werpy and
based research. Whereas in 1996 we extrapolated much of Kurt Selberg have also contributed to the imaging chapters; Dr.
our information from laboratory animal research and human Janny de Grauw contributed to the chapter on synovial fluid and
studies, the majority of this text now provides evidence based serum biomarkers; and Dr. Laurie Goodrich added her expertise
on experimental and clinical research in the horse. This to Chapter 27, and Dr. Jos Malda commented on Chapter 1 and
increases both the appropriateness of the findings and the Dr. van Weeren’s part of Chapter 27. We also wish to acknowl-
clinical translation for the veterinarian. edge Lynsey Bosch for typing and patience and Paula Vander-
The purpose of this book is to redefine the current status linden for typing and organization as we have prepared these
of the continually changing area of developmental and trau- manuscripts. We also thank Dave Carlson for the line drawings
matic joint disease. We are fortunate to have contributors who to go with the radiographs in Chapter 9 and the editorial and pro-
have done much of the original work. New biologic therapies duction staffs of Elsevier with special mention to Penny Rudolph
that are targeted against specific mediators that have been who started this project; Brandi Graham for her great support,
identified with different pathobiologic and biomechanical patience, and editing; and William Drone for copyediting.
etiologies. These basics will be presented but limited to what Drs. McIlwraith, Frisbie, and Kawcak wish to acknowledge
is clinically relevant. the incredible contributions and assistance of faculty and staff
The text begins with a discussion of general anatomy and of the Orthopaedic Research Center and the more recent
physiology of joints as well as biomechanics, followed by the program of Equine Sports Medicine and Rehabilitation. This
pathogenetic pathways of traumatic arthritis and posttrau- team has facilitated acquisition of much of the information in
matic osteoarthritis and the pathologic manifestations of this book and will advance our knowledge for future editions.
joint disease. Osteochondritis dissecans, subchondral cystic Dr. van Weeren also acknowledges the great contributions of
lesions, septic arthritis, and the effect of loading on joint tis- the present and past members of his research team at Utrecht,
sues are then reviewed. The principles of diagnosis follow, with special mention of Dr. Pieter Brama, on whose research
with much increased detail on the current state-of-the-art efforts a large part of the content of Chapter 8 is based.
in clinical examination and intraarticular injection (includ- In addition, Wayne, Dave, Chris, and René are fortunate to
ing simulations based on computed tomography) as well as in be married to experts in this or related areas. Dr. Nancy Good-
imaging, which has probably progressed the most in equine man has been Wayne’s major clinical mentor starting in 1983
joint disease use in the 19 years since the first edition was and has given great professional and personal support. Dave
published. Frisbie thanks Dr. Myra Barrett-Frisbie, and her major contri-
There is a chapter on synovial fluid and serum biomarkers, butions to this text have been previously noted. Chris Kawcak
followed by separate chapters with discussion of the validation is married to Dr. Erin Contino, who is a product of our Equine
of the various treatment options including nonsteroidal antiin- Sports Medicine and Rehabilitation program as well as our
flammatory drugs, intraarticular corticosteroids, hyaluronan, graduate research program and is soon to be a faculty mem-
polysulfated glycosaminoglycan, and pentosan polysulfate. ber at Colorado State University. René van Weeren is married
Newer therapies that are presented for the first time include to Madelon Bitterling, who is both a human and an animal
biologic therapies (including the autologous-conditioned physiotherapist and an expert in veterinary ergonomics.
serum products as well as the platelet-rich plasma products We would also like to recognize the funding agencies that
and mesenchymal stem cells). Various types of rehabilita- have supported our research. This includes Grayson-Jockey
tion including underwater treadmilling as well as a careful Club Research Foundation, American Quarter Horse Associa-
discussion of oral joint supplements and their use in equine tion, United States Equestrian Foundation, and Morris Animal
joint disease are also new materials included for the first time. Foundation, as well as the National Institute of Health. Finances
Chapters 20 through 26 then cover all details on pathogen- limit us answering many important relevant questions and, to
esis, diagnosis, and treatment of the various joint entities by support much of this work, we at the ORC owe it to our fantas-
region including separate chapters on distal limb, fetlock, car- tic donors who contribute to answering these questions. These
pus, elbow and shoulder, tarsus, stifle, and hip. We conclude discretionary dollars have allowed a considerable amount of
with a chapter on joint disease; both current research and the research to be translated into clinical reality here.
xi
SECTION I General Principles of Joint Pathobiology
1
General Anatomy and Physiology of Joints
P. René van Weeren
The horse has always taken a special position among the spe- privileged place in the big family of animal species with which
cies that have been domesticated by humankind. The horse humankind has surrounded itself.
was domesticated rather late, around 3500 BC,1 millennia Where the role of the horse in society has changed pro-
after such species as goat, sheep, and cattle. Unlike these other foundly in the past century, the underlying reasons of its use
species, the main purpose of the horse’s domestication was and popularity have not changed at all. It is still the stamina of
not the provision of edible products or products that could be the animal and athletic capacity of its locomotor system that
somehow transformed into clothing, such as meat, milk, fur, form the basis for almost all present-day use. The most critical
or skin, but for a less tangible commodity: the combination of body systems for athletic performance are the cardiorespira-
physical power and athletic capacity. tory system and the musculoskeletal system. Within the lat-
Horses have been the major power source for all Eurasian ter system, joints are literally pivotal elements. It may not be
and Northern African civilizations since their introduc- surprising that orthopedic malfunctioning or other musculo-
tion from roughly 3500 to 500 BC until the invention of the skeletal disorders account for the vast majority of reasons to
steam engine that started the Industrial Revolution in the late consult an equine vet.3 Of the specific elements of the muscu-
1700s. The ultimate personification of the role of the horse in loskeletal system, joint disorders invariably rank first or sec-
society is perhaps Bucephalus, the legendary horse of Alex- ond in importance (together with tendinopathies, depending
ander the Great, who conquered the vastest land empire the on discipline). Most figures come from the racing industry,4,5
world has ever known. Bucephalus served Alexander who, but the relatively scarce data for sport horses also point in the
according to legend, was the only person able to mount the same direction.6,7 In a survey of U.S. horse owners in 1998 it
stallion, from a young age to its death at the age of 30 after was estimated that 60% of all lameness was related to osteo-
the battle of Hydaspes in what is now Pakistan, 2900 miles arthritis (OA) and approximately $145 million was spent on
from its native Macedonia. There, Alexander named the veterinary bills relating to the problem.8 In this respect, the
city of Bucephala (present-day Jhelum) after him. After the clinical importance of joint disorders in the equine species is
Industrial Revolution horses still remained essential for many very comparable to the situation in humans where musculo-
sectors of human society until after World War II, when the skeletal disorders in general and articular pathologies in par-
combustion engine definitively took over all traditional roles ticular represent an enormous burden to society in terms of
of the horse in warfare, transport, and agriculture. Some loss of quality of life and costs of healthcare with 151 million
have predicted that the loss of its classic duties would make sufferers of OA worldwide.9 For this and a number of impor-
the horse into a zoo species,2 but they were proven entirely tant biologic reasons the horse is increasingly recognized as
wrong by the rapidly increasing popularity of the horse as a a suitable, if not the best, model for human joint disease.10
sports and leisure animal from the mid-1960s onwards. Over This translational aspect of equine joint disease will be dealt
the millennia, humans and horses appeared to have bonded with in more detail in Chapter 27, which discusses arthritis
in a way that goes far beyond economic value or utility and research and future directions in joint disease.
is more profound than with any other domesticated species, This first chapter gives a general introduction into the
with the exception of the dog. Though admittedly the equine anatomy and physiology of the (equine) joint, as a basis for
industry is susceptible to the fluctuations of economic pros- the understanding of the following chapters that address in
perity, this fascination for the equine species is not likely to detail specific disorders, diagnostic possibilities, and thera-
disappear soon, if ever. This obviously guarantees the horse its peutic interventions.
1
2 SECTION I General Principles of Joint Pathobiology
JOINT FUNCTIONS disk and the symphysis of the pubic bones in both humans
and horses. In synovial joints there is no structural connec-
Whereas the necessary stability of the equine musculoskel- tion between the bony parts of the skeleton, but both ends
etal system is provided by the rigid bony components, joints are capped with hyaline cartilage and articulate by gliding
permit motion of these bony components in relation to each over each other although contained in a joint capsule that is
other and, indirectly, the displacement of the entire indi- filled with synovial fluid, a viscous liquid. A sliding bearing in
vidual with respect to the environment, that is, locomotion. mechanical engineering basically functions according to the
To accomplish this, joints have to meet several requirements. same principle.
They have to be as robust as the bony elements of the mus- In a functional sense, there are several other ways to clas-
culoskeletal system, as the forces generated by locomotion sify joints. A common way is according to the degree of
and other (athletic) activities are transmitted through joints motion they permit. Although the following nomenclature
as they are through bones. They also have to allow for smooth is currently seen as obsolete,15 it is still widely used and will
and as frictionless as possible motion of the bony ends that hence be mentioned here. A synarthrosis is a joint permitting
articulate with respect to each other. Lastly, they have a role, little mobility. Most of these joints are of fibrous nature, such
together with other structures, such as the digital cushion in as the sutures that connect the bony components that make
the foot, to mitigate and dampen the accelerations and associ- up the skull. Amphiarthroses are joints that permit more, but
ated vibrations that are generated during the impact peak of still very limited, mobility. They are generally of either fibrous
the stride cycle at hoof landing. This latter aspect has been or cartilaginous nature, with the intervertebral joints (again
relatively well studied in the equine literature.11,12 with the exception of C1-C2) as the best examples. Finally,
All the aforementioned requirements that are at least par- diarthrodial joints permit maximal motion. These are always
tially contradictory (strength comparable to bone, smooth synovial joints and their motion is limited by periarticular or
surfaces for supple gliding, and resilience for shock absorp- intraarticular structures such as capsules or ligaments, but
tion) have to be accommodated in a single structure, which not by the nature of the joint. Virtually all joints of the appen-
is a challenging task. As will be explained, nature deals with dicular skeleton of the horse are diarthrodial joints.
these challenges in an ingenious way, however, at the cost of Other functional classifications are based on the degrees
flexibility and repair capacity. For reasons of clarity the com- of freedom a joint has. Any three-dimensional body in space
ponents that make up a joint will be dealt with separately, but has six potential degrees of freedom within the global coor-
it is important to stress that a joint is more than a collection dinate system: three translations along the x, y, and z axes of
of tissues with separate characteristics and functions. There is the coordinate system, and three rotations around these axes.
common agreement nowadays that the joint should be seen as In aeronautical terms these rotations are indicated as pitch,
a complex multicomposite organ not unlike structures such yaw, and roll. In joints, translations of bony parts with respect
as the liver, kidney or heart.13,14 Within this organ the consti- to each other are limited (but may occur, for instance in the
tuting elements act together to ensure proper joint function. middle carpal joint), but rotations can be substantial and may
There is a strong interplay of all these components in health comprise rotations around more than one axis, as is the case
and disease and mutual influencing of physiologic function- in the hip joint. The horse has evolved as a flight-and-fright
ing; malfunctioning of the components will also inevitably animal specialized in fast motion, for which reason most of
affect the other constituents and hence performance of the the joints of the appendicular skeleton are largely monoaxial,
entire joint at a shorter or longer term. permitting excursions that are basically restricted to flexion-
extension in the sagittal plane.
TYPES OF JOINTS This chapter is limited to the general anatomy and physiol-
ogy of diarthrodial joints only, as the other joint types in the
Joints can be classified in several ways. A gross division can horse hardly, if ever, give rise to clinical problems.
be made between classification according to structural char-
acteristics, that is, the type of tissue(s) that form the inter- EMBRYONIC JOINT DEVELOPMENT
face between the articulating bony parts of the skeleton, and
classification according to function, or the degree and type of The axial and limb skeleton is derived from the embryonic
movement joints allow. paraxial and lateral plate mesoderm, which is the precur-
The currently used basic classification is three major cat- sor tissue of, among other tissues, the hyaline cartilage that
egories, which are fibrous joints with the bone connected by is found in diarthrodial joints. The mesenchymal progenitor
dense connective tissue, cartilaginous joints where cartilage is cells, originating from the lateral plate mesoderm, differenti-
the interface, and synovial joints in which there is a fluid-filled ate into chondrocytes that form a cartilaginous skeletal anla-
cavity.15 In the horse, the articulations between the bodies of gen as precursor for the later bony skeleton and connecting
the vertebrae that make up the axial skeleton are fibrous joints, diarthrodial joints.16 Joint formation occurs when cells at the
with the exception of the articulation between the first and future joint site start to flatten and form a region that is dis-
second cervical vertebrae (C1-C2), which is a synovial joint. tinct from the adjacent cartilaginous areas.17 This zone, once
A cartilaginous joint has an interface consisting of hyaline morphologically distinct, is called the interzone. The cells in
or fibrous cartilage; examples are the human intervertebral this zone lose their chondrogenic phenotype and cease the
CHAPTER 1 General Anatomy and Physiology of Joints 3
expression of collagen type II. The interzone is further char-
acterized by the expression of growth/differentiation fac-
tor 5 (Gdf5), Wnt9a, double cortin, and versican, whereas Trabecular bone
matrilin-1 is not expressed anymore.16,18 The importance
of the interzone for joint formation has been demonstrated
Joint capsule
unequivocally by the experimental removal of the interzone
from the elbow joint in chicken embryos, which led to the
Synovial Subchondral
fusion of the humerus with the radius and the ulna in the membrane bone plate
absence of joint formation.19 Articular
The moment when interzone development starts dur- Joint cavity cartilage
containing
ing embryonic development varies per species. Recently,
synovial fluid
equine embryonic development has been mapped in detail
using magnetic resonance imaging.20 When taking the day
in which ovulation was first detected as day 0 of pregnancy
and hence of embryonic life (E0), it has been shown that at
E40 the interzone is fully formed and consists of three dis- FIGURE 1-1 Schematic representation of a diarthrodial joint.
tinct layers: the inner interzone (II) that will develop into the (Adapted from: De Grauw J.C. (2010). Molecular monitoring
of equine joint homeostasis. Thesis, Utrecht University.)
joint cavity, intraarticular structures, and articular cartilage,
and two adjacent outer interzones, which are precursors to
the epiphyseal growth cartilage and will eventually turn into and temporomandibular joints. These constituting struc-
bone.21 Using laser capture microdissection to harvest tis- tures of the joint will be discussed separately in the following
sue samples from outer and inner interzones, respectively, it paragraphs.
was shown that the mRNA expression patterns of both tissue
Articular Cartilage
types varied markedly for genes related to chondrogenesis.
Further, several genes involved in cell adhesion, transcription The functional characteristics of a construction are largely
regulation, and various signaling pathways were expressed determined by the interplay of the material properties of the
differentially. The top 25 genes expressed more in the outer building blocks or components that construction is made
than in the intermediate interzone were mostly associated of and the way these components are arranged and inter-
with endochondral ossification, cartilage, and growth plate connected, that is, the architecture of the construction. For
matrix composition. Examples are genes for matrilin-1 and structured tissues, such as articular cartilage or bone, this is
3, BMP5, and Col2al. They also partake in Wnt/b-catenin similar. However, as in all living tissues, the situation is more
signaling, bone morphogenetic protein (BMP) signaling, complex as cellular action, driven by a wide variety of cues
and sonic hedgehog signaling, which are essential regulatory and effected through various signaling pathways, determines
pathways for chondrogenesis and osteogenesis.21 This infor- tissue homeostasis and the response to external stimuli. If
mation is important for the further development of regenera- that response can somehow not cope with the demands made
tive techniques for articular lesions in which the full recovery by these stimuli, pathology may ensue.
of the original structure and function is still a major challenge The major components of the extracellular matrix (ECM)
(see also Chapter 27). of articular cartilage are collagen, proteoglycans (PGs), and
water. Water content varies from 70% to 80%, depending on
PRINCIPLES OF JOINT ANATOMY age. The other components account for approximately 50%
(collagen) and 35% (PGs) on a dry weight basis. The remain-
Figure 1-1 presents a semischematic and simplified draw- ing 15% consists of about two thirds (10% of total dry weight)
ing of a diarthrodial joint. The basic structures common to of glycoproteins (substances such as proteinases and inhibi-
all synovial joints are layers of articular cartilage covering tors of these, growth factors, specific molecules such as fibro-
the ends of the articulating bones that together constitute the nectin, lubricin, cartilage oligomeric protein [COMP], etc.)
joint, subchondral bone beneath this cartilage, synovial fluid Minor fractions are minerals (3%), lipids (1%), and miscella-
that surrounds the articulating bone ends, and some struc- neous components (1%).22 The cellular component of articu-
ture that restrains the synovial fluid within the joint. This lat- lar cartilage is relatively small and accounts for approximately
ter structure will often be a joint capsule, but other structures 1% to 12% volume percentage, depending on the location
may serve this purpose as well, as is the case of the proximal within the joint and the depth in relation to the surface.22
interphalangeal joint that has no capsule but in which the
Layered Composition of Articular Cartilage
synovial fluid is retained by the ligamentous and tendinous
structures that surround the joint. Additional structures that Whereas cartilage macroscopically is seemingly a homo-
serve principally to stabilize the joint and to restrict motion in geneous tissue, there are large differences in structure and
unwanted directions are collateral or other periarticular liga- composition from the surface down to the transition to the
ments, intraarticular ligaments, such as the cruciate ligaments subchondral bone. Classically, four layers or zones are dis-
in the femorotibial joint, and menisci, as in the femorotibial cerned, although the transitions between these layers are
