nucleus arthroplasty volume i
DESCRIPTION
Nucleus Arthroplasty Volume ITRANSCRIPT
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NucleusArthroplasty
Volume I: Fundamentals
Technology
in Spinal Care
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1 Introduction
2 About the Editors
C H A P T E R 1 3 How the Disc Degenerates
C H A P T E R 2 10 Nucleus Arthroplasty Motion Preservation Technology
versus Nucleus Replacement
C H A P T E R 3 12 Nucleus Arthroplasty Technology from the U.S. Regulatory Viewpoint
C H A P T E R 4 17 Fundamentals of Reimbursement
C H A P T E R 5 21 Worldwide Orthopedic and Spine Market
C H A P T E R 6 27 Nucleus Arthroplasty Technologies
35 Conclusion
36 Contributing Authors
Table of Contents
This monograph series is a groundbreaking project in therapidly emerging field of non-fusion spinal surgery. Thefull range of nucleus replacement technologies is examined
with discussion on surgical techniques, detailed information
on each cutting-edge device technology, indications, and
patient selection criteria.
Nucleus Arthroplasty Technology in Spinal Care is
published for the medical profession by Raymedica, LLC,
Minneapolis, MN 55431.
The views expressed in this series are those of the authors
and do not necessarily represent those of Raymedica, LLC.
Copyright 2006 Raymedica, LLC. All rights reserved.
Printed in U.S.A.
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Introduction
1
The first documented works describing the diagnosis andtreatment of the spine, spinal disorders, and spinal instabilitydate back to 1900-2500 B.C. Interestingly, the documents recom-
mended against the treatment of spinal cord injury. The develop-
ment of therapeutic treatments has a long history starting with
the cane, the first load-sharing device. Today, our efforts to
improve therapies to treat spine disease persist. We continue to
recognize problems, identify issues, and define variables in an
effort to better understand spinal degeneration and to develop
innovative solutions that utilize a wide array of materials and
technologies. Our field has had a rich history of advancements,
accomplishments, and inventiveness. We owe a great debt to the
pioneers who, armed with little more than a detailed knowledge
of anatomy, heralded in the era of spinal surgery. Their trials,
errors, innovations, and teachings have guided our efforts to
ultimately improve clinical outcomes.
Early on, it was recognized that the disc played a vital role in overall
spine health.With great effort and ingenuity, the unique anatomical,
biomechanical, and physiological properties of the disc were eluci-
dated and incorporated into elegant treatment algorithms.We now
have access to an almost overwhelming flow of information about
lumbar disc arthroplasty from countless sources. Central to the evo-
lution of therapies is a better appreciation of the complexities of the
lumbar disc. By combining knowledge gleaned from anatomical dis-
section, biochemical processes, and resultant physiology with a disci-
plined foundation in biomechanics, we have created a fabric of
understanding never before enjoyed. Spine arthroplasty is now an
important and evolving area within the treatment of spinal disor-
ders. This sub-discipline represents the coalescence of many areas of
study focused on the development of new and exciting solutions to
address clinical problems.
These significant advances in our understanding of the spine rep-
resent a culmination of efforts occurring across many fronts. Our
increased understanding of the biological factors at work in disc
disease has been a driving force in the development and emer-
gence of new materials and delivery methods. The critical role
that advanced biocompatible alloys, polymers, and viscoelastic
hydrogels play in the innovation of disc arthroplasty technologies
cannot be over emphasized.
Technological advancements have played a vital role in supporting
and expanding our knowledge of motion preserving disc technolo-
gies. The latest imaging technologies allow a much more detailed
appreciation of pathological processes, such as disc degeneration,
and provide the ability to monitor the results of an intervention.
Computerized finite element analysis offers a risk-free environment
in which to test hypotheses and predict clinical impact. Biochemical
advancements yield an intimate understanding of the chemical envi-
ronment including chemical mediators and potential intervention
portals. This wealth of knowledge can be used to great advantage
when developing disc arthroplasty technologies.
Not to be overlooked, the socioeconomic challenges involved in the
development of new technologies, such as the Nucleus Arthroplasty
motion preservation system, have also become more apparent.
The all important variable of proper patient selection continues to
require constant reassessment and vigilance. Increasingly, third-party
payers control access to care and treatment choice to an alarming
degree. Such considerations can no longer be ignored in the quest
for ideal patient management methods.
This publication has been constructed to provide an overview
of the foundational elements of Nucleus Arthroplasty motion
preservation technology including an understanding of the
degenerative process, current treatment solutions, systematic
treatment approaches, regulatory processes, and reimbursement
concerns. In addition, part one of this series will provide insight
into the potential market and the current players working in the
forefront of Nucleus Arthroplasty development activities. This is
an incredibly exciting field as technologies focused on the repair
and replacement of the diseased disc nucleus will catapult us far
beyond the treatment options we have available today.
In conclusion, we can say that the spine arthroplasty specialist
of today is well prepared to deliver the most advanced solutions
to the clinical puzzle of disc disease with technologies based on
a rich tradition of innovation and compassion coupled with a
tremendous wealth of physiological knowledge and assessment
tools. As spine surgery evolves from mechanical solutions to
therapeutic solutions both surgeons and patients will benefit.
We hope you will find this series on Nucleus Arthroplasty
technology to be a valuable asset.
Reginald J. Davis, MD, FACSCHIEF OF NEUROSURGERY
Baltimore Neurosurgical Associates, PA
Baltimore, MD 21204
Federico P. Girardi, MDASSISTANT PROFESSOR
OF ORTHOPEDIC SURGERY
Hospital for Special Surgery
New York, NY 10021
Federico P. Girardi, MDReginald J. Davis, MD, FACS
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2Reginald J. Davis, MD, FACS
Dr. Davis is founder of Baltimore Neurosurgical Associates, chief
of Neurosurgery at the Greater Baltimore Medical Center, and a
faculty member at the Johns Hopkins School of Medicine and
the University of Maryland. He is a Fellow of the American
College of Surgeons and a Diplomate of the American Board
of Surgery. Dr. Davis received his medical degree from Johns
Hopkins University School of Medicine, Baltimore, Maryland.
He has broad experience in advanced procedures such as spinal
stabilization, intradiscal electrothermal therapy, and microendo-
scopic discectomy and has conducted physician training pro-
grams on these procedures. His professional affiliations include
the AANS-CNS Section on Disorders of the Spine, the American
Association of Neurological Surgeons, the Congress of
Neurological Surgeons, and the North American Spine Society.
Federico P. Girardi, MD
Dr. Girardi is assistant attending orthopedic surgeon at the
Hospital for Special Surgery, New York, New York where he spe-
cializes in the treatment of spinal disorders including degenera-
tive disc disease (DDD), spinal deformities, metabolic fractures,
and spinal tumors. Dr. Girardi received his medical degree from
the Universidad Nacional de Rosario, Rosario, Argentina.
He has performed extensive clinical research in the areas of min-
imally invasive surgery, clinical outcomes, and spinal imaging.
He is also interested in basic research on bone, disc, and nerve
tissue regeneration and in the investigation of alternatives to
spinal fusion for the treatment of DDD. His professional affilia-
tions include the North American Spine Society, Scoliosis
Research Society, the European Spine Society, the International
Society for the Study of the Lumbar Spine, and the Spine
Arthroplasty Society.
Raymedica has selected Reginald J. Davis, MD, FACS andFederico P. Girardi, MD, to edit this series of monographson Nucleus Arthroplasty technology, because of their special
interest in this dynamic area of medicine. Both Drs. Davis and
Girardi are noted for their expertise in spine surgery and
advanced training in minimally invasive surgical techniques.
They are well respected for their clinical work and travel
widely to speak and train other physicians.
About the Editors
Reginald J. Davis, MD, FACS Federico P. Girardi, MD
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3Chapter 1 How the Disc Degenerates
Jeff S. Silber, MDASSISTANT PROFESSOR
Department of Orthopaedic Surgery
Chief, Division of Spine Surgery
Long Island Jewish Medical Center
New Hyde Park, NY 11040
Kamal Dagly, MDRESIDENT ORTHOPAEDIC SURGERY
Department of Orthopaedic Surgery
Long Island Jewish Medical Center
New Hyde Park, NY 11040
Zoe Brown, MDSPINE RESEARCH FELLOW
Department of Orthopaedic Surgery
The Rothman Institute
Department of Orthopaedic Surgery
Philadelphia, PA 19107
Archit Patel, MDSPINE RESEARCH FELLOW
Department of Orthopaedic Surgery
The Rothman Institute
Department of Orthopaedic Surgery
Philadelphia, PA 19107
Ravi PatelMEDICAL STUDENT
Department of Orthopaedic Surgery
Thomas Jefferson University
Philadelphia, PA 19107
Alexander R. Vaccaro, MDPROFESSOR
Department of Orthopaedics and Neurosurgery
Co-Chief, Division of Spine Surgery
Co-Spine Fellowship Director
Co-Director Delaware Valley Regional
Spinal Cord Injury Center and
The Rothman Institute
Department of Orthopaedic Surgery
Philadelphia, PA 19107
MOLECULAR BIOLOGY OF DISC DEGENERATION
An understanding of the biology of disc degeneration canprovide a better understanding of the diagnosis and treat-ment of low back pain (LBP). The 23 intervertebral discs that lie
between each vertebral segment provide flexibility and increase
physically in size when progressing from the cervical spine to the
sacrum.1 The disc consists of two distinct anatomic regions that
work in unison. They include the fibrous outer annulus fibrosus
and the softer inner cartilaginous nucleus pulposus. The annulus
fibrosus in the lumbar spine has up to 25 layers known as
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4lamella containing mostly type I collagen arranged in a parallel
pattern.2 The intricate cross-linked configuration of the fibrils
allows the intervertebral disc to resist tensile forces incurred dur-
ing lumbar spine bending and torsional movements. The inner
nucleus pulposus contains predominantly type II collagen fibers
arranged in a more random fashion. The fibers are surrounded
by a matrix rich in proteins known as proteoglycans. These pro-
teoglycans bind water and have a high water content in a normal
intervertebral disc. This gives the disc its characteristic stiffness
and viscoelasticity allowing compressive resistance to axial loads.3
The concentration of proteoglycans and the water binding capac-
ity of the disc increases when progressing from the outer annulus
fibrosus to the inner nucleus pulposus. In contrast, the concentra-
tion of type II collagen decreases from the inner nucleus to outer
annulus fibrosus. The collagen content of the nucleus is highest
in the cervical spine and decreases in the lumbar spine, while the
proteoglycan content increases in the lumbar spine. The high pro-
teoglycan content in the lumbar spine is ideal due to its water
binding capacity, which allows for an increased resistance to axial
compressive loads where it is most needed.
Over time, proteolytic damage to the fibrillar collagens of the
annulus occurs as a result of collagenase activity. This leads to
a decrease in collagen cross-linking and a weakening in the bio-
mechanical stability of the intervertebral disc and acceleration
of the normal process of disc degeneration or aging. As the disc
ages, the amount of aggregated proteoglycans decreases while
the content of non-aggregated proteoglycans increases leading to
lower osmotic or water binding capacity and a loss of compressive
resistance in the lumbar intervertebral disc.4
The vascularity of the intervertebral disc diminishes as it develops
and grows. The predominant source of intervertebral nutrition
during normal growth is through the vasculature of the vertebral
endplates. However in the adult, calcification of the endplates
occurs, and nutrient uptake and waste elimination occur through
diffusion. This leads to anaerobic metabolism taking a more
prominent role during which lactate production produces an
acidic environment, making proteinases more active and resulting
in further disc degeneration.5
The lumbar intervertebral disc has developed the ability phyloge-
netically to withstand high compressive axial forces. This is accom-
plished by its ability to convert compressive loads into tensile
stresses by utilizing the osmotic pressure of the interstitial fluid
and the proteoglycans located in the nucleus pulposus. As the disc
degenerates further, the annulus fibrosus becomes stiffer and the
osmotic pressure of the nucleus pulposus decreases causing imbal-
ances in load transfer and resulting in increased stresses to the
bony elements of the vertebral endplates. It has been shown that
when heavy loads are applied to the intervertebral disc, the normal
disc biology is disrupted leading to an increase in catabolic
enzymes and an acceleration in intervertebral disc degeneration.6
Certain individuals may be genetically predisposed to the catabolic
events of disc degeneration. Polymorphisms of the vitamin D
receptor, aggrecan gene, type IX collagen, and MMP-3 (matrix
metalloproteinase-3) have all been implicated in accelerated
intervertebral disc degeneration. Furthermore, studies have
shown increased rates of degenerative disc disease in siblings
of affected individuals and a strong correlation in twins.
Chronic discogenic back pain has been linked to many factors
including anatomic structural changes, inflammatory mediators,
and nervous ingrowth into the outer annulus fibrosus. Production
of inflammatory mediators such as interleukin (IL)-1, IL-8,
fibroblast growth factor and intracellular adhesion molecule
(ICAM)-1 by mononuclear cells infiltrating a herniated disc may
also lead to inflammation and pain.7 IL-1 has also been shown to
increase the rate of matrix breakdown as well as decrease the pro-
duction of proteoglycans, thereby, affecting the water content in
the nucleus pulposus. Additionally, herniated discs also produce
nitric oxide synthetase, an enzyme known to lead to the formation
of free radicals which cause direct damage to cell membranes and
matrix proteins.8 These herniated disc fragments can also generate
high levels of phospholipase A2, an enzyme which facilitates the
formation of pro-inflammatory prostaglandins and leukotrienes
both of which are important mediators in the production of pain.
T H E L U M B A R I N T E R V E R T E B R A L D I S CH A S D E V E L O P E D T H E A B I L I T YP H Y L O G E N E T I C A L LY T O W I T H S TA N DH I G H C O M P R E S S I V E A X I A L F O R C E S .
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5STAGES OF DISC DEGENERATION
Kirkaldy-Willis described the widely accepted degenerative cas-
cade (pathophysiological model) that occurs in the intervertebral
disc. The cascade is divided into three stages based on the
amount of damage or degeneration to the disc and facet joints at
a given point in time.9 This cascade of individual motion segment
degeneration is thought of as a continuum rather than as three
clearly definable and separate stages.
Stage I (Dysfunctional)
The first stage is known as the dysfunctional stage and occurs
when the initial changes of intervertebral disc degeneration begin.
This occurs between 20-30 years of age and is described by cir-
cumferential fissuring or tearing of the outer annulus fibrosus.
This may result from repetitive vertebral endplate injury leading
to a disruption in the intervertebral vascular supply and impair-
ment of the normal disc metabolism. These pathophysiologic
changes result from years of repetitive microtrauma and usually
present as acute mechanical low back pain episodes or going out
phases. In the initial stages, acute episodes of low back pain are
self limited, and improve with minimal intervention. However,
the pain experienced in this stage may be severely debilitating
because of the large innervation to the outer-third of the annulus
via the sinuvertebral nerves. Over time, the circumferential tears
may combine and form larger radial tears while the inner nucleus
pulposus loses its water-retaining properties due to changes in
aggregating proteoglycans. These changes, mostly a decrease in
amount and organization in proteoglycans, are thought to occur
due to an imbalance in the MMP-3 (matrix metalloproteinase-3)
and TIMP-1 (tissue inhibitor of metalloproteinase-1) proteins
seen in the normal nucleus pulposus. Magnetic resonance imaging
(MRI) studies during this stage may reveal a high intensity zone
(HIZ) lesion in the posterior outer annulus fibrosus and decreased
signal intensity on T2 weighted images (disc desiccation) with or
without disc bulging and without herniation.
Stage II (Instability)
The second stage, known as the instability stage, represents more
severe tissue damage. This stage occurs later in life between 30
and 50 years of age. Intervertebral disc changes occur as the
result of multiple annular tears and delamination of the layers.
Vertebral segment instability occurs, and this results in a decline
in the amount of nuclear proteoglycan composition with a
resulting loss of water content. Increased force transfer to the
annulus occurs with the subsequent loss of intervertebral disc
height. The patient in this stage of degeneration also presents
with periods of low back pain which is usually more intense,
more protracted in duration and requires more aggressive inter-
vention. These episodes occur more frequently, and MRI studies
reveal further loss of intervertebral disc height, a darker disc,
and possibly a herniation.
Figure 1
Stage II: A lateral plain radi-ograph demonstrating partialloss of disc height at the L5-S1interspace. There is radiographicevidence of vertebral bodyendplate deformation and earlyanterior osteophyte formation.
Stage II (Instability)
Figure 2
Stage II: Sagittal MRI demon-strating decreased disc T2 sig-nal intensity at both the L4-L5and L5-S1 levels as a result ofdisc desiccation. There is alsoloss of disc space height atthese levels.
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6Stage III (Stabilization)
The third stage, known as the stabilization stage, is the endpoint
in the intervertebral disc degenerative cascade and is exemplified
by endstage tissue damage and attempts at repair. Further nucleus
pulposus resorption occurs with worsening intervertebral disc
space narrowing, fibrosis, endplate irregularities, and the forma-
tion of osteophytes. This stage usually occurs after the age of 60
and may present with symptoms of neurogenic claudication or
radiculopathy from central, lateral recess, and/or foraminal
stenosis. Lower extremity symptoms may prevail over low back
pain in this stage.
DIAGNOSIS
The relationship of lumbar disc degeneration and LBP remains
controversial. This is due to the poor correlation between the
presence of degenerative disc disease (DDD) on imaging studies
and the report of symptoms in the general population. Numerous
studies have documented that a high percentage of asymptomatic
patients have abnormal findings on imaging studies including the
presence of DDD.10-15 However, some authors have reported a
strong correlation between low back pain and the presence of
a HIZ lesion seen in the outer annulus fibrosus. This finding is
thought to represent an annular tear which may lead to sympto-
matic DDD and LBP.16-20 In contrast, Carragee et al20 looked at
the incidence of HIZ annular tears on MRI in a recent prospec-
tive study. He reported the presence of a HIZ lesion in 42 symp-
tomatic patients with LBP but also in 54 asymptomatic patients.
The prevalence of a HIZ lesion was 59% in the symptomatic
group and 24% in the asymptomatic group. The authors con-
cluded that the prevalence of a HIZ lesion in asymptomatic
individuals with DDD was exceedingly high, and the presence
of an HIZ lesion was not meaningful for clinical use.20
Although approximately 80% of adults will experience low back
pain, only 1-2% will undergo an invasive surgical procedure. The
decision to undertake surgical management of DDD is extremely
patient dependent and requires great study due to the ubiqui-
tousness of imaging evidence of spinal degenerative disease. The
pre-surgical work-up should include a thorough history relating
to any spinal complaints and a physical examination followed by
Figure 3
Stage III: Lateral radiograph ofthe lumbar spine with signifi-cant loss of disc height at theL4-L5 interval. Sclerosis is seenat the vertebral endplates andwithin the facet joints.
Stage III (Stabilization)
Figure 4
Stage III: Sagittal MRI demonstrat-ing markedly decreased T2 signal atthe L4-L5 disc space resulting fromendstage disc desiccation.Mildlyincreased T2 signal is seen in theadjacent L4 and L5 vertebral bodiesconsistent with edema.
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7a working diagnosis and directed imaging studies. Imaging stud-
ies may include plain radiographs, MRI, computed tomography,
and provocative discography. The relative indications for the
surgical management of lumbar DDD for primarily axial back
pain include the following:
1. Chronic low back pain of discogenic origin for more than
six months that has failed a reasonable comprehensive non-
operative treatment program. This non-operative treatment
program may include physical therapy, chiropractic manip-
ulation, activity modification, a back education program,
oral medications, and/or epidural spinal injections.
2. The absence of neurological signs and symptoms (radicular
findings).
3. Evidence of abnormal disc morphology or DDD on MRI.
4. A concordantly positive provocative discogram which
includes normal control levels above and/or below the
degenerative disc in question.
5. A reasonably normal psychological profile including an
appropriate, educated, and motivated patient that has realis-
tic goals and expectations.21 A pre-surgical psychological
evaluation may also be strongly advised.
6. No litigation/workers compensation claims.
PROCEDURAL CHOICES
If the patient is eligible for surgical intervention, a decision must
be made on the appropriate surgical procedure. The surgical pro-
cedure must address the proposed pain generator which is usu-
ally the intervertebral disc. Many surgical strategies have resulted
in less than satisfactory long-term outcomes. This has led to the
development of newer alternative technologies including nucleus
pulposus replacement, lumbar intervertebral disc replacement,
annular fibrosus augmentation, intradiscal electrothermal annu-
loplasty (IDET), and interbody fusion techniques. Currently, the
favored treatment methods involve removing the pain generator,
the intervertebral disc, through a fusion procedure and using a
variety of bone graft alternatives/extenders or maintaining
motion with an intervertebral disc arthroplasty.
INTERBODY STABILIZATION (FUSION) PROCEDURES
At present, lumbar interbody fusion procedures are the primary
surgical treatment alternative for symptomatic lumbar degenerative
disc disease.22-27 Interbody fusion techniques include stand alone
Anterior Lumbar Interbody Fusion (ALIF), stand alone Posterior
Lumbar Interbody Fusion (PLIF), instrumented (pedicle screw)
Posterior Lumbar Interbody Fusion, Transforaminal Lumbar
Interbody Fusion (TLIF), and anterior/posterior or circumferential
fusions. Which fusion technique results in the highest fusion rate,
the fewest complications, and the best outcomes is continuously
debated among surgeons. Some spine surgeons favor anterior or
posterior-only approaches, while others favor an anterior/posterior
circumferential fusion procedure. Interbody fusion procedures have
been shown to be biomechanically superior to posterolateral inter-
transverse fusions alone in providing support against axial loads.23
Interbody fusion devices or cages come in a variety of shapes and
may be trapezoidal, ramped, lordotic, or cylindrical and are placed
either as a single device or paired. They can be inserted from
either an anterior or posterior approach. Minimally invasive cage
introduction methods designed to decrease surgical morbidity and
improve functional outcomes have been introduced.
The use of stand-alone cages without adjunctive pedicle screw
instrumentation has met with an unacceptable rate of failure
due to continued instability or symptomatic pseudarthrosis, espe-
cially when used over multiple segments or in the setting of cir-
cumferential instability (spondylolisthesis, lateral listhesis).25
The most predictable method of ensuring an interbody fusion is
a 360-degree or combined anterior and posterior spinal fusion.
Interestingly, surgeons continue to debate whether a solid fusion
is necessary to achieve a satisfactory outcome or whether a stable
interspace alone is sufficient.
Anterior surgical procedures may be performed using open or
laproscopic methods. The theoretical advantage of placing an
anterior interbody cage as compared with a posterior interbody
fusion technique is that it optimizes the ability to prepare the
intervertebral endplates through direct visualization.
I N T E R B O D Y F U S I O N P R O C E D U R E S H AV E B E E NS HOWN TO B E B I OM E C H AN I C A L LY S U P E R I O RT O P O S T E R O L A T E R A L I N T E R T R A N S V E R S EF U S I O N S A L O N E I N P R O V I D I N G S U P P O R TA G A I N S T A X I A L L O A D S .
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8Additionally, anterior placement provides a biomechanical advan-
tage in restoring lumbar lordosis more efficiently. An anterior
approach often allows for placement of a much larger spacer than a
posterior delivered cage, because there is no need to retract neural
elements. Some surgeons also feel that there is a benefit in avoiding
surgical trauma to the posterior paraspinal musculature. The ante-
rior approach, however, has its own unique complications including
the possibility of retrograde ejaculation, vascular and abdominal
visceral injuries, and post-operative incisional hernias.
The transforaminal lumbar interbody fusion (TLIF) allows place-
ment of an interbody device from the posterior approach but more
laterally than the typical PLIF technique. The proposed advantage
of the TLIF over the PLIF technique is the minimal need for neural
retraction required for cage placement. Originally, the TLIF tech-
nique called for placement of two interbody devices through a
bilateral approach. However, it is quite frequently performed by
placing a single obliquely oriented interbody cage through a unilat-
eral approach. The TLIF approach allows access to the interver-
tebral disc space lateral to the thecal sac. Studies have shown that
anterior placement of a single oblique cage using supplemental
pedicle screw instrumentation approximates the stiffness and
strength of a normal intact spinal segment.28Adjunctive poste-
rior pedicle screw instrumentation is always recommended when
performing a TLIF procedure, as it is with a PLIF.
The standard surgical exposure for posterior interbody fusions
usually involves a posterior midline incision and bilateral
paraspinal soft tissue dissection in order to expose the posterior
elements in a subperiosteal manner. Alternatively, newer tech-
niques involving minimal incisions exploit the use of specially
designed metal tubes or dilators to gradually separate the poste-
rior soft tissues (muscle fibers) creating an appropriately-sized
tunnel. These less invasive techniques may not only reduce
iatrogenic soft tissue injury, but also decrease post-operative
pain, intraoperative blood loss, and allow for faster recovery, as
compared with traditional open techniques. Unfortunately,
working through small tubes reduces the visual field and may
lead to increased surgical times. Interbody devices and pedicle
screws may all be inserted through these less invasive tube
retractor techniques. Complications specific to the posterior
interbody approach include dural lacerations, epidural fibrosus,
and nerve root injuries.29 Rarely, penetration through the ante-
rior annulus resulting in vascular and visceral injuries has also
been reported.
LUMBAR NUCLEUS PULPOSUS/INTERVERTEBRALDISC REPLACEMENT
Lumbar nucleus pulposus and artificial lumbar disc replacement
procedures were introduced to provide pain relief through a sta-
ble motion-sparing reconstruction of the intervertebral segment
via tensioning of the annulus fibrosus or stabilization of the
lumbar motion segment. Unfortunately, the extremely large and
complicated forces that exist in the native lumbar intervertebral
disc present a significant engineering challenge in creating an
ideal implant. Presently, several different types of disc prostheses
designed for use in nucleus pulposus replacement or total disc
arthroplasty procedures are either FDA approved or are being
investigated in clinical studies.
The PDN prosthetic disc nucleus, a nucleus replacement device
for symptomatic degenerative disc disease, has met with good suc-
cess.30 The majority of treated patients reported improved low
back pain and better overall function at two-year follow-up
based on Oswestry and Visual Analog scales. The PDN device
consists of hydrogel core center encased in a high molecular
weight polyethylene sleeve. This device has been shown to shrink
and swell during normal loading and unloading of the lumbar
spine mimicking the healthy human intervertebral disc. It is
hoped that future studies will shed light on the optimum surgical
treatment strategy for symptomatic DDD.
A recent prospective randomized study has demonstrated the
equivalence of an ALIF or total disc arthroplasty in the man-
agement of lumbar DDD. In a controlled, prospective, random-
ized study, 31 60 patients with one-level symptomatic discogenic
lumbar axial back pain were treated with either an ALIF or
an anterior SB Charite artificial disc replacement. The authors
demonstrated comparable improved functional outcome measures
in both treatment groups.
S T U D I E S H A V E S H O W N T H AT A S I N G L EO B L I Q U E C A G E P L A C E D A N T E R I O R LYW I T H S U P P L E M E N TA L P E D I C L E S C R E WI N S T R U M E N TAT I O N A P P R O X I M AT E S T H ES T I F F N E S S A N D S T R E N G T H O F A N O R M A LI N TA C T S P I N A L S E G M E N T .
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CONCLUSION
The vast majority of patients with LBP either experience com-
plete resolution of their symptoms or require a short period of
non-operative treatment such as anti-inflammatory medication
or physical therapy. However, the most effective method of sur-
gical intervention is still unclear. It may turn out that nucleus
replacement methods suffice for the majority of patients that
present with recalcitrant low back pain allowing for the use of
technically simpler surgery than afforded by performing a total
disc arthroplasty procedure.
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10. Erkintalo MO, Salminen JJ, Alanen AM, Paajanen HE, Kormano MJ.Development of degenerative changes in the lumbar intervertebral disc:results of a prospective MR imaging study in adolescents with and withoutlow-back pain. Radiology. 1995 Aug;196(2):529-33.
11. Salminen JJ, Erkintalo M, Laine M, Pentti J. Low back pain in the young.A prospective three-year follow-up study of subjects with and without lowback pain. Spine. 1995 Oct 1;20(19):2101-7; discussion 2108.
12. Savage RA,Whitehouse GH, Roberts N. The relationship between the mag-netic resonance imaging appearance of the lumbar spine and low back pain,age and occupation in males. Eur Spine J. 1997;6(2):106-14.
13. Jensen MC, Brant-Zawadzki MN, Obuchowski N, Modic MT, Malkasian D,Ross JS. Magnetic resonance imaging of the lumbar spine in people withoutback pain. N Engl J Med. 1994 Jul 14;331(2):69-73.
14. Borenstein DG, O'Mara JW Jr, Boden SD, Lauerman WC, Jacobson A,Platenberg C, Schellinger D, Wiesel SW. The value of magnetic resonanceimaging of the lumbar spine to predict low-back pain in asymptomatic sub-jects : a seven-year follow-up study. J Bone Joint Surg Am. 2001 Sep;83-A(9):1306-11.
15. Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW. Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospectiveinvestigation. J Bone Joint Surg Am. 1990 Mar;72(3):403-8.
16. Lam KS, Carlin D, Mulholland RC. Lumbar disc high-intensity zone: thevalue and significance of provocative discography in the determination ofthe discogenic pain source. Eur Spine J. 2000 Feb;9(1):36-41.
17. Schellhas KP, Pollei SR, Gundry CR, Heithoff KB. Lumbar disc high-intensityzone. Correlation of magnetic resonance imaging and discography. Spine.1996 Jan 1;21(1):79-86.
18. Saifuddin A, Braithwaite I, White J, Taylor BA, Renton P. The value of lumbarspine magnetic resonance imaging in the demonstration of anular tears.Spine. 1998 Feb 15;23(4):453-7.
19. Aprill C, Bogduk N. High-intensity zone: a diagnostic sign of painful lumbardisc on magnetic resonance imaging. Br J Radiol. 1992 May;65(773):361-9.
20. Carragee EJ, Paragioudakis SJ, Khurana S. 2000 Volvo Award winner inclinical studies: Lumbar high-intensity zone and discography in subjectswithout low back problems. Spine. 2000 Dec 1;25(23):2987-92.
21. Kwon BK, Vaccaro AR, Grauer JN, Beiner J. Indications, techniques, and out-comes of posterior surgery for chronic low back pain. Orthop Clin NorthAm. 2003 Apr;34(2):297-308.
22. Tsantrizos A, Baramki HG, Zeidman S, et al. Segmental stability and com-pressive strength of posterior lumbar interbody fusion implants. Spine.2000;25:1899-1907.
23. Enker P, Steffee AD. Interbody fusion and instrumentation. Clin Orthop.1994;300:90-101.
24. Zeidman SM. Intradiscal biomechanics: anterior vs. posterior approach-decisionmaking ALIF vs. PLIF and why? Augmentation vs. stand alone implant.Proceedings of the 16th Annual Meeting of the Federation of SpineAssociations. 2001;10.
25. Shaffrey CI. Indications for threaded interbody devices. Proceedings of the16th Annual Meeting of the Federation of Spine Associations. 2001;9.
26. Zdeblick TA, David SM. A prospective comparison of surgical approach foranterior L4-L5 fusion: laparoscopic versus mini anterior lumbar interbodyfusion. Spine. 2000;25:2682-7.
27. Regan JJ. Laparoscopic lumbar fusion: single surgeon experience in 127 con-secutive cases. Proceedings of the 68th Annual Meeting of the AmericanAcademy of Orthopedic Surgeons. 2001;469.
28. Savas PE, Harris BM, Hilibrand AS, et al. Transforaminal lumbar interbodyfusion: the effect of various instrumentation techniques. Proceedings of the15th Annual Meeting of the North American Spine Society. 2000;216-7.
29. Albert TJ. Complications of cages and dowels. Instructional Course Lecture#209 of the 68th Annual Meeting of the American Academy of OrthopedicSurgeons. 2001.
30. Batterjee KA, Ray CD, Osman MA, et al. One year followup on 17 Saudipatients implanted with a prosthetic disc nucleus. Proceedings of the AnnualMeeting of the International Society for the Study of the Lumbar Spine.2000;114.
31. McAfee PC, Fedder IL, Saiedy S, Shucosky EM, Cunningham BW. SB Charitdisc replacement: report of 60 prospective randomized cases in a US center. JSpinal Disord Tech. 2003 Aug;16(4):424-33.
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Chapter 2 Nucleus Arthroplasty MotionPreservation Technologyversus Nucleus Replacement
The purpose of this chapter is to help clinicians understandthe difference between Nucleus Arthroplasty motion preser-vation technology and nucleus replacement. While the discussion
may seem subjective, the difference between the two terms is vast
and can have a significant impact on a clinical practice.
Nucleus replacement is much like any other joint replacement
within the body. It is meant to replace one biologic component with
another that mimics normal biological function. However, simply
replacing the disc nucleus with a prosthetic device may not address
the problems incurred by patients suffering from degenerative disc
disease (DDD). Unfortunately, DDD is a problem that is not limited
to one portion of the vertebral disc or a single spinal level. Rather,
it is a complex disease that must be
addressed comprehensively.
Nucleus Arthroplasty motion preservation
technology goes beyond nucleus replacement
and involves a comprehensive systematic
approach to DDD. It is not only the implant
that is important in Nucleus Arthroplasty
technology, but the consideration of many factors including proper
patient selection, indications, surgical technique/approach, and
post-operative rehabilitation. Nucleus Arthroplasty technology
involves a complete spectrum of treatment starting with the initial
consultation in the surgeons office and ending with follow-up and
monitoring six months post-surgery. The systematic approach of
Nucleus Arthroplasty technology is better suited to providing pre-
dictable and successful outcomes than the device-only approach
of nucleus replacement.
N U C L E U S A R T H R O P L A S T Y M O T I O NP R E S E R V A T I O N T E C H N O L O G Y G O E SB E Y O N D N U C L E U S R E P L A C E M E N TA N D I N V O LV E S A C O M P R E H E N S I V ES Y S T E M AT I C A P P R O A C H T O D D D .
Reginald J. Davis, MD, FACSCHIEF OF NEUROSURGERY
Baltimore Neurosurgical Associates, PA
Baltimore, MD 21204
Federico P. Girardi, MDASSISTANT PROFESSOR
OF ORTHOPEDIC SURGERY
Hospital for Special Surgery
New York, NY 10021
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A discussion of the evolution of hip replacement surgery can set
the stage for the discussion of changes currently occurring
in Nucleus Arthroplasty technology. In the 1970s, a degener-
ated hip joint was treated with a hip replacement device. One
of the biggest problems with early hip replacements was that
the cement used to attach the device to the femur and acetabulum
loosened, resulting in performance problems. The clinical issues
were not simply related to the product but also involved post-
operative patient care. These problems were addressed with a
systematic approach to hip replacement. Uncemented hip
replacement devices with a porous coating that allowed bone in-
growth were developed and replaced devices that were cemented
into place. The new generation implant was designed to function
with the patient and was not merely a device within the body. In
addition to improving the implant-to-patient match, specific
post-operative rehabilitation protocols were developed and opti-
mized. The surgeon provided specific and detailed instructions on
when the patient should put weight on the leg and when he or she
should start walking.
Nucleus replacement therapy is currently in an analogous state
to hip replacement surgery in the 1970s. A systematic approach
involving the whole continuum of care is required to achieve
optimum clinical outcomes with Nucleus Arthroplasty technol-
ogy. Nucleus Arthroplasty system technology is much more
complex than hip replacement given the intricacies of the spine.
It is therefore necessary to address all variables that can affect
the outcome of the treatment. For example, optimal patient
selection and surgical technique without proper rehabilitation
will lead to minimal success. Similarly, thorough post-operative
rehabilitation without appropriate patient selection will also
result in a poor outcome.
While this may seem like common sense, most companies
developing Nucleus Arthroplasty devices have not reached such
a conclusion. Most products are simply nucleus replacement
devices and not arthroplasty systems. Given that each implant
may treat a slightly different indication and require a different
surgical technique means that a unique system involving exten-
sive clinical experience must be developed for each product.
Most disc replacement technologies are not ready for transfor-
mation into Nucleus Arthroplasty systems. While companies
can refine their devices, instruments and surgical techniques
through pre-clinical testing, the indications, patient selection
criteria, and post-operative protocol can only be discerned
through actual clinical experience.
Several issues must be addressed in order to advance the field of
Nucleus Arthroplasty motion preservation system. First, the
process of disc degeneration must be better understood. Not all
DDD is the same, just as not all cases of spondylolisthesis and
herniation are the same. Variations in the process of DDD make
it difficult to treat the condition and to achieve predictable out-
comes. Second, nucleus replacement devices currently being
developed have crossover indications and applications that make
it difficult for the clinician to determine which device is best
suited for a particular patient at a given stage of the disease
process. Additionally, how a patients DDD is classified can
impact patient selection criteria for Nucleus Arthroplasty therapy.
There is a large difference between what is called mild DDD and
what is called early stage DDD. Some clinicians believe severe
disc collapse must be present before a patient is considered to
be in the early stages of DDD. However, in many cases, a patient
may experience pain for an extended period of time, even
though radiographic evidence of DDD is lacking. These patients
may still be good candidates for Nucleus Arthroplasty non-
fusion technology.
Due to the need to develop specific patient selection and indica-
tion criteria for specific devices, the future for the Nucleus
Arthroplasty market will be more individualized as the years
pass. The goal is for a company to have a multitude of device
sizes that can be implanted using a variety of approaches and
implantation techniques. In this way, the implant and surgical
approach can be tailored to address specific patient requirements.
Once again, clinical data is imperative to develop the requisite
patient and product selection criteria. Without valid evidence,
it is more difficult to develop a Nucleus Arthroplasty system that
provides reproducible and successful clinical results. After these
issues are addressed, it is expected that the indications for
Nucleus Arthroplasty systems will be wider than those for total
disc replacements. As more technologies attain long-term clinical
history, the evolution from nucleus replacement to Nucleus
Arthroplasty motion preservation technology will become
clearer to the orthopedic industry, as other arthroplasty
technologies have in the past.
T H E F U T U R E F O R T H E N U C L E U SA R T H R O P L A S T Y M A R K E T W I L L B E M O R EI N D I V I D U A L I Z E D A S T H E Y E A R S G O B Y.
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REGULATORY OVERVIEW
At the current time, the Food and Drug Administration (FDA)considers the termnucleus arthroplasty as broadly applicableto any device that replaces the nucleus pulposus while preserving the
surrounding annulus. Such devices are intended to reduce pain and
increase function without fusing the spine. The key features of
the FDAs definition include:
Device location (i.e., placement in the nucleus space)
General intent of the device (i.e., not intended to fuse the spine)
Although devices may be varied in their designs, materials, tech-
nological characteristics, and implantation methods, any device
that meets the basic criteria outlined above will be regarded by
the FDA as a Nucleus Arthroplasty system.
The regulatory pathway for marketing approval of Nucleus
Arthroplasty devices involves a Premarket Application (PMA)
submission to the FDA. A PMA should establish reasonable
assurance of safety and effectiveness for a novel therapy or
device, typically using valid scientific evidence that is collected in
a well-controlled clinical trial. FDA approval for an Investigational
Device Exemption (IDE) will allow unapproved devices to be
studied in a clinical trial to gather this data. Such trials are
designed to measure patient pain and function at selected time
points following implantation of the Nucleus Arthroplasty device.
This data is most often compared to a control based on the
current standard of care.
Chapter 3 Nucleus Arthroplasty Technologyfrom the U.S. Regulatory Viewpoint
Glenn A. Stiegman, III, MSVICE PRESIDENT, REGULATORY AFFAIRS
Musculoskeletal Clinical Regulatory Advisers, LLC
New York, NY 10022
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Currently there are no FDA approved Nucleus Arthroplasty
devices. As of August 2006, four companies are in the process
of conducting five U.S. IDE pilot clinical trials of Nucleus
Arthroplasty technologies.
Although Nucleus Arthroplasty devices may offer many benefits
compared to the current standard of care, device design issues and
clinical concerns must be addressed in order to gather the data
necessary to demonstrate safety and effectiveness. These issues and
concerns should be addressed by means of appropriately-designed
pre-clinical and clinical studies.
CHALLENGES FOR MANUFACTURERS AND THE FDA
Even in the initial stages of development for new and innovative
therapies, the FDA must require that the preliminary safety of the
device be established prior to starting a human clinical trial. This
represents a formidable obstacle for most device manufacturers
because of limitations in testing and characterization methods.
Often when dealing with novel technologies, industry standards
and FDA guidance documents are not available to provide direc-
tion in regard to validation methods. In the case of Nucleus
Arthroplasty devices, the variety of materials, designs, and surgical
implantation techniques have made it virtually impossible to cre-
ate standardized testing that could be applied to the diversity of
devices. Creating tests that are clinically relevant is also challeng-
ing for the device manufacturer. Safety profiles may be very dif-
ferent for each device design; however, testing must be designed
and conducted to demonstrate that devices will not cause unfore-
seen risks. The devices intended use should direct both pre-clini-
cal and clinical evaluations, including material selection, device
design, pre-clinical testing, surgical technique, and clinical study
design. A clear understanding of the devices intended use will
also facilitate regulatory negotiations, and will offer the FDA the
opportunity to provide clear feedback during the pre-clinical and
clinical study design stages.
In the face of all these challenges, it is important for the manufac-
turer to work diligently and consult with the FDA early in the
process to develop appropriate pre-clinical testing. Ideally, this
effort will yield results that are scientifically and clinically relevant,
and that ultimately demonstrate the safety of the device.
REGULATORY REQUIREMENTS
Regulatory requirements for conducting clinical trials and subse-
quent PMA applications include extensive preliminary design
validation and pre-clinical studies. The following are some of the
many challenges involved:
Identifying the appropriate patient population
Selecting appropriate device materials
Designing the optimal device and placement technique
Planning and implementing pre-clinical testing
Implementing the clinical trial
PATIENT POPULATION
Paramount to the development of new treatment alternatives is a
clear understanding of the capabilities and success of available
treatment options in contrast to the unmet patient needs.Within
the confines of degenerative disc disease, the potential playing field
seems to be exceptionally large as there is a significant gap between
the conservative and surgical treatment options that are currently
implemented to cover a wide range of indications and potential
degenerative disease stages.
NUCLEUS ARTHROPLASTY MOTION PRESERVATION TECHNOLOGIESCURRENT U.S. IDE PILOT STUDIES
APPROVAL
COMPANY TECHNOLOGY INDICATION DATE
1 Spine Wave, Inc. NuCore Adjunct To Microdiscectomy Feb-06
2 Raymedica, LLC HydraFlex Not Publicly Available Jun-06
3 Spine Wave, Inc. NuCore Degenerative Disc Disease Jun-06
4 Disc Dynamics, Inc. DASCOR Not Publicly Available Aug-06
5 Pioneer Surgical Technology NUBAC Not Publicly Available Aug-06
prepared by MCRA, LLC
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In general terms, Nucleus Arthroplasty technologies represent a
host of potential products designed to address degenerative disc
disease. Ideally, the shape, form, and function of each device will
be tailored to meet the individual needs of the patient population
at a specific stage within the degenerative disc cascade.
The success of any Nucleus Arthroplasty device will be directly
tied to the ability of a particular technology to be properly
matched to a defined patient indication. However, trying to
identify the correct patient population and the appropriate time
for surgical intervention are among the biggest clinical chal-
lenges facing those who study Nucleus Arthroplasty devices.
From the regulatory perspective, device manufacturers will be
challenged to both define the intended treatment population
and establish evidence of improvement with the proposed
device in relation to the current standard of care.
DEVICE MATERIAL
Determining the appropriate material is one of the key issues
involved in engineering Nucleus Arthroplasty devices, since inap-
propriate material selection can contribute to potential failure
modes. Each material presents its own regulatory hurdles because
of the lack of validated characterization methods. As material
technologies have advanced, testing standards and characteriza-
tion methods have remained relatively stagnant. Therefore, older
or non-validated testing methods must be used which may pose
risks to the patient if not performed adequately. While the FDA
can provide valuable feedback about the potential risks and con-
cerns associated with each device, appropriate material character-
ization activities (i.e., mechanical, animal, and material tests)
must be determined by the manufacturer.
There are several options that can be used to describe and charac-
terize the device material. General biocompatibility evaluation
and testing as recommended in the ISO Standard 10993 is
required and should be performed at the initial stages of material
development. Animal testing is often required to further study the
material. Ideally, animal testing can be performed in a functional
model in which the device is implanted using similar methods to
those intended for human use. Establishing a functional model
that appropriately evaluates the device in an animal can be difficult
due to the differences in spinal anatomy and biomechanics
between humans and animals. In such instances where an appro-
priate functional evaluation cannot be performed, animal testing
may be conducted in which the primary focus is to evaluate the
effects of material particulate in potential worst-case wear debris
conditions. The particulate test usually consists of implanting an
appropriate and clinically relevant wear debris particle quantity,
shape, and size distribution into the spine of a small animal, such
as a rabbit. The intent of this test is to eliminate potential risks
associated with the material.
DEVICE DESIGN
Obviously, the material and design elements of any Nucleus
Arthroplasty device are intimately linked. The broad spectrum
of available materials has resulted in many different Nucleus
Arthroplasty device designs. The challenge is to determine the
best device design for the intended patient treatment popula-
tion. Each individual design will have specific implications in
regard to indications, patient selection, surgical technique and
post-operative rehabilitation.
Device design performance requirements will also be strongly
influenced by the indications of the selected treatment popula-
tion. As such, it is critical to completely define the design ration-
ale for the device. This can prove to be a daunting task when
working with Nucleus Arthroplasty technologies as the load envi-
ronment could be greatly influenced by many factors such as the
level of the disease, bone quality, placement of the device, and
the degenerative disease stage. This situation is further exacer-
bated by the limited information and clinical experience avail-
able to use in defining appropriate design parameters. All of
these factors can affect the clinical results, welfare of the patient,
and ultimately, the success of a particular device.
N U C L E U S A R T H R O P L A S T Y M O T I O NP R E S E R V A T I O N D E V I C E S M A Y O F F E RA G O O D A L T E R N AT I V E T O T R E A TI N D I C A T I O N S W H E R E T H E R E I S N OR E L I A B L E O R E F F E C T I V E S TA N D A R DO F C A R E .
E A C H I N D I V I D U A L D E V I C E D E S I G N W I L LH AV E S P E C I F I C I M P L I C AT I O N S I N R E G A R DT O I N D I C AT I O N S , PAT I E N T S E L E C T I O N ,S U R G I C A L T E C HN I Q U E AND PO S T- O P E R AT I V ER E H A B I L I TAT I O N .
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In addition to assessing the potential mechanical challenges
imposed on the design, all potential factors associated with the
surgical approach and device delivery method must also be scru-
tinized. The device may have an ideal design based on biome-
chanical factors, however, the surgical approach, surgical
instruments, and overall surgical procedure may significantly
affect patient outcomes.
PRE-CLINICAL TEST PLANNINGAND IMPLEMENTATION
Preliminary data on Nucleus Arthroplasty devices can be gath-
ered from various studies worldwide. However, most of these
studies have not been long-term, prospectively defined, con-
trolled, randomized, or powered with the sample size required
to make a strong conclusion about the device being studied.
In order to adequately show the device design is safe, potential
failure modes and clinical risks must be described and mitigated.
Mechanical testing is generally used to evaluate device mechanics
under clinically relevant and/or worst-case loads and displace-
ments. The type of test that is required will vary depending on the
particular device design and intent. A complete evaluation of the
device in a biomechanical model such as a cadaver spine is
important to understand the device mechanics and simulated
anatomical performance. Such testing may also provide valuable
information about the device, surgical approach, proposed surgi-
cal instruments, and surgical technique. Loading the spine in var-
ious scenarios may also provide insight into potential clinical
failure modes. While many of these failure modes can be
addressed mechanically, there may still be instances in which the
device performs perfectly in a simulated setting yet shows signifi-
cant failures in subsequent patient evaluations.While mechanical
testing has significant value, comparison of the results to a clinically
successful device or scenario is almost impossible.
CLINICAL TRIAL IMPLEMENTATION
After completing the appropriate pre-clinical testing to charac-
terize device materials, validate the design, and gather prelimi-
nary safety data, a device manufacturer must provide all this
information to the FDA. These results will be reviewed by the
FDA and used to justify approval of the human clinical trial.
The data collected in the trial will be used to demonstrate the
safety and effectiveness of the therapy in the PMA application.
IDE PILOT
Since Nucleus Arthroplasty devices are still considered a novel
therapy that utilize a wide array of designs, materials, and
implantation techniques, the FDA will likely require a pilot study
to ensure that these parameters have been optimized. This is
especially true in cases when bench testing is not adequate to
characterize device safety. The IDE pilot study, also known as a
feasibility study, is a limited human clinical study designed to
answer specific questions associated with the device or implanta-
tion method and to establish the preliminary safety of the device
and surgical technique. The length of a pilot study can vary from
six months to two years and is largely dependent on the ques-
tions or concerns that are being addressed. Specific concerns
about device material, mechanics, or biological effects may
require a study of longer duration while concerns associated
with items such as the surgical technique may be relatively short.
As indicated, a pilot study may assist in addressing concerns that
cannot be tested on the bench. For example, published literature
has reported device expulsions with certain Nucleus Arthroplasty
device designs. However, this particular device failure mode did
not occur during bench, biomechanical, or animal testing.
Clearly, additional bench testing in such situations does not
positively contribute to the existing knowledge base. Thus,
small pilot studies are conducted to provide data that cannot
be obtained strictly through pre-clinical testing.
T H E A B I L I T Y T O U S E T E C H N O L O G I C A L LY A D V A N C E D M AT E R I A L S , D E S I G NP A R A M E T E R S , S U R G I C A L A P P R O A C H E S , A N D I N S T R U M E N TAT I O N A F F O R D E DB Y N U C L E U S A R T H R O P L A S T Y M O T I O N P R E S E R V A T I O N T E C H N O L O G Y C A NM I N I M I Z E T H E R I S K S A S S O C I A T E D W I T H I M P L A N TAT I O N .
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IDE PIVOTAL
After the pilot study has been completed and all questions or
concerns regarding device safety have been addressed, the manu-
facturer must conduct a clinical study comparing the device to a
valid control. The clinical trial design of the pilot study is often
very similar to the IDE pivotal study. As discussed earlier, select-
ing a control group can prove to be very difficult in the case of
Nucleus Arthroplasty devices. Proper selection of a control group
is extremely important as the treatment results for the control
will serve as a basis for comparison in regard to device safety and
effectiveness. Selection of a control group that does not closely
match the indications and intended patient population will make
it difficult for the FDA and Centers for Medicare and Medicaid
Services (CMS) to determine the clinical meaning behind the
data and how it would translate to the general U.S. population.
As noted above, prior to selecting a control group, it is impera-
tive that the device indications be appropriately defined. The
device indications dictate the process of identifying a proper
control group and directing the design of the pivotal clinical
trial, length of the study, and primary and secondary endpoint
selections. Most Nucleus Arthroplasty devices are indicated for
mild to moderate DDD or instances of acute disc herniation.
Use of Nucleus Arthroplasty devices to address such indications
will require a two-year clinical study. In addition, post-mar-
ket follow-up for a minimum of five years may also be
requested. Appropriately describing the indications for the
intended patient population may well determine the success of
the study and the device itself.
Lastly, establishing the appropriate study endpoints is very
important, as they provide the foundation for the demonstration
of safety and effectiveness as well as supporting evidence for the
device labeling claims. If a manufacturer chooses to exclude rele-
vant endpoints in order to avoid risks or save money, the trial
results may be inadequate to support safety or effectiveness, and
may greatly weaken the manufacturers ability to make label-
ing claims regarding the device performance. Therefore, a
complete and thorough study of all potential study parameters
is recommended, including radiographic, economic, and clinical
assessment measurements.
SUMMARY
Nucleus Arthroplasty motion preservation technology has the
potential to be an excellent treatment alternative for patients in
the mild to moderate stages of DDD. Today, this represents a
relatively large unmet opportunity for advancements in patient
care. However, there are still many unanswered questions that
must be addressed before this device technology can be considered
a viable treatment alternative. As more clinical data becomes
available, manufacturers and the FDA will continue to develop
the expertise required to more appropriately design and evaluate
such devices. Until that time, individual devices must be examined
and studied very carefully on a case-by-case basis.
P R O P E R S E L E C T I O N O F A C O N T R O LG R O U P I S E X T R E M E LY I M P O R TA N T A ST H E T R E A T M E N T R E S U L T S F O R T H EC O N T R O L W I L L S E R V E A S A B A S I S F O RC O M PA R I S O N I N R E G A R D T O D E V I C ES A F E T Y A N D E F F E C T I V E N E S S .
N U C L E U S A R T H R O P L A S T Y M O T I O N P R E S E R V A T I O N T E C H N O L O G Y H A ST H E P O T E N T I A L T O B E A N E X C E L L E N T T R E A T M E N T A L T E R N AT I V E F O RP A T I E N T S I N T H E M I L D T O M O D E R AT E S TA G E S O F D D D . T O D A Y, T H I SR E P R E S E N T S A R E L A T I V E LY L A R G E U N M E T O P P O R T U N I T Y F O RA D V A N C E M E N T S I N P A T I E N T C A R E .
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THE IMPORTANCE OF REIMBURSEMENT
Obtaining optimal reimbursement is critical to the adoptionof a new device or technology. Even though a particulardevice has received regulatory approval to be marketed, there is
no guarantee that it will be adopted by surgeons if the practice or
hospital cannot obtain reimbursement from third-party payers.
The increasing costs of procedures and devices will make some
surgeons wary of using a product if the prospect of reimburse-
ment is uncertain. However, as the medical device industry con-
tinues to invent and innovate, acquiring reimbursement has
become more difficult. Obtaining proper reimbursement for a
new device is imperative if device manufacturers hope to make
an impact on the market. This is particularly true for orthopedic
devices and technologies because payers are responsible for 90%
of orthopedic procedures. Understanding the reimbursement
process is crucial for medical device companies involved in this
market sector.
Companies can make a multitude of mistakes when seeking reim-
bursement, especially for a groundbreaking treatment such as
Nucleus Arthroplasty technology. Companies may assume that
receiving Food and Drug Administration (FDA) approval will
automatically guarantee reimbursement from payers, but this is
not necessarily the case. A lack of understanding about the clinical
and economic data required to obtain optimal reimbursement can
result in the demise of a Nucleus Arthroplasty company. Therefore,
Nucleus Arthroplasty companies, especially those seeking new or
Chapter 4 Fundamentals of Reimbursement
Kelli HallasVICE PRESIDENT
Field Reimbursement Services
Emerson Consultants, Inc.
Eden Prairie, MN 55344
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additional codes, must be aware of what government and private
payers require before granting reimbursement for a new device
or technology.
REIMBURSEMENT BASICS
This chapter will review and discuss the basic elements of reim-
bursement in regard to Nucleus Arthroplasty motion preserva-
tion technologies. Most often reimbursement is thought of as a
single entity when in actuality it is composed of the following
three distinct elements:
Coverage
Coding
Payment
Reimbursement is the end result of the interaction of these drivers.
COVERAGE
Coverage refers to a third-party payers decision on whether or
not to pay for a particular procedure, device, therapy, or service
under the health services or benefits that are arranged, provided,
or paid for through a health insurance plan. A coverage determi-
nation is based on whether the procedure, device, therapy, or
service in question is considered a medical necessity. To be con-
sidered medically necessary, the goods or services should meet
the following requirements/conditions:
Appropriate and necessary for the symptoms, diagnosis, or
treatment of a medical condition;
Meet the standards of good medical practice within the med-
ical community in the service area;
Unbiased regarding convenience to the plan member or plan
provider;
Most appropriate level or supply of service that can safely be
provided; and
Provided for the diagnosis or direct care and treatment of the
medical condition.
Note that all of the conditions must be satisfied for the good or
service to be considered a medical necessity.
Coverage can be favorable, unfavorable, or limited in nature. It may
be issued formally within a policy or granted informally on a case-
by-case basis. The coverage of Nucleus Arthroplasty technologies
will vary by payer.Whereas some payers may approve the procedure
for coverage on an individual basis, others will consider the proce-
dure investigational or experimental and deny coverage. This
increased scrutiny is typical for emerging treatments and technolo-
gies.
Obtaining a positive coverage decision is critical to the success of
any technology. The following criteria are considered by payers
when making coverage decisions:
The technology must have final approval from the appropriate
governmental bodiesthe FDA in the U.S.
Scientific evidence must permit conclusions concerning the
effect of the technology on health outcomes.
The technology must improve the net health outcomes.
The technology must be as beneficial as any currently
established alternatives.
Improvement must be attainable outside of the investi-
gational setting.
Peer-reviewed data published in a U.S. journal must be
available, preferably from a multi-centered, double blind,
controlled study conducted in the U.S.
It should also be noted that, although a product may not be
intended for significant use in the Medicare population (patients
age 65 and older), the coverage policies developed by the Centers
for Medicare and Medicaid Services (CMS) heavily influence the
coverage decisions of private payers. Therefore, it is important
that companies consider the impact the technology will have on
the Medicare population during clinical trial design. The final
coverage decision made by CMS on any technology may greatly
impact the companys overall bottom line sales.
CODING
Coding represents the reimbursement language that payers and
providers use to communicate. Codes explain the why and the
what, and are universally accepted among physicians, hospitals,
and payers. Providers report on procedures by using various types
of codes both during clinical trials and after FDA approval. Codes
are dynamic and may change even if the product or procedure
does not. In the long term, it is critical that companies work
closely with CMS, the American Medical Association (AMA),
and relevant professional societies to ensure the development
of appropriate coding recommendations.
M O S T O F T E N R E I M B U R S E M E N T I ST H O U G H T O F A S A S I N G L E E N T I T Y W H E NI N A C T U A L I T Y I T I S C O M P O S E D O F T H EF O L L O W I N G T H R E E D I S T I N C T E L E M E N T S :C O V E R A G E , C O D I N G A N D PA Y M E N T .
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During a clinical trial, a code that accurately describes a proce-
dure or service may not exist, so an unlisted procedure code
will be reported. This is most often the case with break-
through and emerging technologies. However, if the appropri-
ate governing body (CMS or AMA) feels that an existing code
can accurately describe the investigational procedure, they may
recommend the use of that code during the clinical trial. In
such instances, it is highly recommended that companies com-
municate with CMS, the AMA, and professional societies, prior
to making any coding recommendations to providers.
Hospitals and physicians use different coding systems (ICD-9-
CM and CPT-4 codes) to report on their work. Each of these
systems will be described separately along with the codes to
report Nucleus Arthroplasty technologies.
Hospitals use ICD-9-CM procedure codes to describe inpatient
surgical, diagnostic, and therapeutic procedures (admitted >24
hours). ICD-9-CM codes are controlled by CMS. During a clini-
cal trial, requests can be submitted to CMS for the creation or
modification of an ICD-9-CM code to allow for accurate classifi-
cation of a new procedure. Formal applications are accepted twice
a year. FDA approval is not required to obtain an ICD-9-CM code
for an inpatient procedure.
CPT-4 codes are used by both physicians and hospital outpatient
departments to describe surgical, non-surgical, and diagnostic
procedures. CPT-4 codes are controlled by the AMA. If the AMA
decides that a procedure is closely related to an existing proce-
dure in consumption of resources, it may recommend use of the
existing code to report the procedure. If the procedure is differ-
ent and distinct from any current coding descriptions, it will rec-
ommend use of an unlisted procedure code during the clinical
trial for tracking and reporting purposes. In the case of Nucleus
Arthroplasty technology, the unlisted procedure code is reported
by the surgeon and will encompass all resource utilization to per-
form the procedure inclusive of the discectomy.
After the clinical trial has been completed, either a professional
society or an external party can file a formal request for either a
new code or modifications to an existing code if the product or
procedure has:
Received FDA approval
Published U.S. peer-reviewed data
Documented widespread use
Support of the professional society
The codes used to report Nucleus Arthroplasty technologies are
listed above in Table 1.
PAYMENT
Payment is determined by contractual terms between healthcare
providers and payers. These arrangements can take different
forms. Examples of hospital payment methodologies include:
Case rate A payment is arranged to cover a specific pro-
cedure, technology, or diagnosis.
Discounted fee for service The payment equals the
amount billed less a pre-negotiated discount.
Fee schedule The facility is paid a flat payment for the
patients admission regardless of resources used or length of
stay (DRG) involved.
Per diem The facility is paid a flat rate per day.
Examples of physician payment methodologies include:
Capitation The physician is paid a certain amount per
member per month to cover the costs of care.
Case rate The surgeon has contracted a fixed fee for a spe-
cific procedure.
Discounted fee for service The payment equals the
amount billed less a pre-negotiated discount.
Fee schedule The physician receives a pre-determined pay-
ment for a particular service.
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TABLE 1. CODES TO REPORT NUCLEUS ARTHROPLASTY TECHNOLOGIES
Insertion of partial spinal prosthesis, lumbosacral; includes nuclear replacement device lumbar; partialartificial disc prosthesis (flexible) lumbar, and replacement.
Revision or replacement of artificial disc prosthesis, lumbosacral; removal of (partial or total) spinaldisc prosthesis with synchronous insertion of new (partial or total) spinal disc prosthesis lumbosacral;repair of previously inserted spinal disc prosthesis, lumbosacral.
Unlisted procedure of the spine.
CODE TYPE NUMBER DESCRIPTION
84.64
84.68
22899
ICD-9-CM Procedure(hospital)
ICD-9-CM Procedure(hospital)
CPT-4(physician)
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In the hospital environment, Medicare pays hospitals according
to the DRG (Diagnostic Related Group) methodology. The
DRG system is intended to classify patients into clinically cohe-
sive groups that demonstrate similar patterns of consumption
of hospital resources and length of stay. According to the
Medicare payment system, Nucleus Arthroplasty technology
will be assigned to one of the DRGs listed above in Table 2.
REIMBURSEMENT FOR NEW DEVICES
When a groundbreaking device is substantially more expensive
than devices that are already on the market, companies will
usually seek a new code to receive proper reimbursement.
However, because claims information does not yet exist, many
companies will apply for an add-on payment, which is a tem-
porary provision for new technologies. This additional pay-
ment gives hospitals and surgeons in private practices in the
U.S. an incentive to use products that have recently received
FDA approval. In order to receive an add-on payment, the
product must be:
New,
Substantially improved relative to the existing technology,
diagnosis, or treatment, and
Of sufficient cost.
Add-on payments are difficult to obtain and require sufficient
clinical and economic data in order to prove to payers that such
a payment is justified.
THE CURRENT REIMBURSEMENT STATUS OFNUCLEUS ARTHROPLASTY TECHNOLOGY
It is helpful to consider the status of Nucleus Arthroplasty tech-
nology in order to gain a better appreciation of the current
reimbursement environment for this new technology. Nucleus
Arthroplasty motion preservation technologies are continuously
emerging. Unlike other spine procedures, this breakthrough
technology was not recognized by CMS until October 2004. It
was at this time that CMS created a new subcategory of procedure
codes to classify spine disc replacement technologies including
total and partial replacements.
Although codes were created to enable tracking of Nucleus
Arthroplasty procedures, CMS has collected little claims data
specific to this ICD-9-CM code and technology. This is
because, until recently, no nucleus replacement technologies
have received approval to begin an Investigational Device
Exemption (IDE) clinical trial in the U.S. Due to several recent
approvals, patient outcomes impacting coverage decisions can
now be tracked, and economic data can be collected to ensure
appropriate payment.
Ultimately, it is the responsibility of the industry and health care
providers to assist CMS in making critical coverage and reim-
bursement decisions impacting this technology. Industry must
ensure that economic data is collected and a solid reimburse-
ment strategy is integrated into the early stages of clinical trial
design and product development. Hospitals and physicians must
adhere to coding guidelines set forth to report the procedures.
All activities that take place during the clinical trial phase will
directly impact payer decisions made after FDA approval and will
ultimately affect the economics of this new technology. CMS
requires data to assist payers in making appropriate decisions. To
ensure positive coverage and payment decisions, this data must be
concise, compelling, and show substantial clinical improvement
over the current gold standard. Therefore, design and execution
of a clinical trial can either make or break a technology.
CONCLUSION
The reimbursement landscape for Nucleus Arthroplasty tech-
nologies will continue to evolve. Although a hospital procedure
code exists for the technology; coverage, payment, and physician
CPT-4 codes have yet to be determined. In the end, having a
well-designed reimbursement strategy that engages the efforts
of physicians, professional societies, and industry will have a
positive impact on reimbursement for this technology.
TABLE 2. DRG ASSIGNMENT FOR
NUCLEUS ARTHROPLASTY TECHNOLOGIES
DRG DESCRIPTION
499 Back and neck procedures, except spinal fusion
with complications.
500 Back and neck procedures, except spinal fusion
without complications.
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21
OVERVIEW
Over the past 15 years, internal fixation with spinal implantshas been used at an accelerated rate in spinal fusion proce-dures. In the last two years, the advent of non-fusion technologies,
including artificial discs, Nucleus Arthroplasty motion preserva-
tion technology and dynamic stabilization systems, have canni-
balized revenues from traditional fixation and interbody fusion
(IBF) markets. Based on historic data, the orthopedic sector is
trending towards an industry that will be classified by anatomy.
Currently, orthopedics can be divided into four major segments:
Large bone and joint - Hip and knee replacements and
ancillary technologies
Spine - Fusion technologies and now evolving towards
motion preserving technologies
Small bone and joint - From the finger to the shoulder and
from the toe to below the knee joint
Cranio - Maxillo facial
Chapter 5 Worldwide Orthopedicand Spine Market
Federico P. Girardi, MDASSISTANT PROFESSOR
OF ORTHOPEDIC SURGERY
Hospital for Special Surgery
New York, NY 10021
Viscogliosi Bros., LLCNew York, NY 10022
I N T H E L A S T T W O Y E A R S , T H E A D V E N T O F N O N - F U S I O NT E C H N O L O G I E S , I N C L U D I N G A R T I F I C I A L D I S C S , N U C L E U SA R T H R O P L A S T Y M O T I O N P R E S E R V AT I O N T E C H N O L O G Y A N DD Y N A M I C S TA B I L I Z AT I O N S Y S T E M S , H A V E C A N N I B A L I Z E DR E V E N U E S F R O M T R A D I T I O N A L F I X AT I O N A N D I N T E R B O D YF U S I O N ( I B F ) M A R K E T S .
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22
The chart below shows the 2006 estimated market size of the
orthopedic sector by segment. The large bone & joint and spine
sectors are expected to account for the lions share of revenue with
90% of the market. It is anticipated that the orthopedic sector will
have the single largest impact on the global healthcare industry
over the next decade, generating over $100 billion in revenues
worldwide. Future growth is highly dependent on both innovation
and distribution.We can expect to see consolidation in this sector,
which will create efficiencies in distribution and set the stage for
large-scale multinational companies to focus on the entire muscu-
loskeletal system. These companies will work to develop a multi-
faceted arsenal of pharmaceutical, biotech, and nanotech solutions.
Ultimately, the orthopedic sector will grow through life-changing,
surgeon-developed inventions, and the adoption, production, and
global distribution of these devices to patients who demand not
only pain relief, but also the restoration of motion.
The worldwide spine market is estimated to be a $5.8 billion
industry in 2006 and is expected to grow an average 15% to 20%
annually. While historically, this market segment has experienced
a 15% annual growth rate, certain niche markets have been
growing as fast as 40% to 100% per year. The spine market in
2006 is 58 times larger than it was in 1990 when revenues totaled
a mere $100 million. Despite this dramatic increase, this market
is poised for significantly greater growth in the near future due
to a variety of reasons including:
A philosophical revolution toward non-fusion technologies
The availability of new technologies globally to treat
expanding indications
A trend in spine surgery toward less invasive procedures
A demographic increase in the number of patients with
back pain
A continuation of intense scientific interest in the study of
spine and back pain
The increased awareness of successful treatment methods
and technologies among spine surgeons
The interest of surgeons and patients in long-term outcomes
In the last few years, the international spine market has seen the
introduction of non-fusion technologies, including Nucleus
Arthroplasty motion preservation system, artificial discs, and
dynamic stabilization systems. The goal of these motion preserva-
tion technologies is to stabilize the spine yet allow for movement.
Although spinal fusion is a highly documented and proven form
of treatment for many patients, spine surgeons have expressed
significant interest in pain relieving therapies designed to preserve
the natural motion of a given spinal segment while restoring disc
height and stability. Of particular interest are non-fusion therapies
focused on the treatment of patients with mild or moderate disc
conditions. These new motion preserving technologies can be
divided into three broad product categories:
Dynamic stabilization
Nucleus Arthroplasty technology
Total disc replacement (TDR)
It is our belief that these non-fusion technologies are starting to
cannibalize revenues from the traditional fixation and interbody
fusion markets.
U.S. LUMBAR SPINE TREATMENT CONTINUUM
For many years, neurosurgeons and orthopedic spine surgeons
have recognized the limitations of fusion procedures for treating
back pain and have been actively seeking alternatives. While
todays spine market is focused on fusion, we believe this will
change dramatically over the next several years as non-fusion
devices are introduced and proven to be more effective and bene-
ficial for patients. This will significantly affect the industrys
reliance on fusion revenues and will force the current industry
leaders to reevaluate their product portfolios in order to maintain