Artigo de atualização / update ARTICLE
Adjacent segment disease of the lumbar spine:
genetic versus biomechanical theories
Síndrome transicional da coluna lumbar:
teoria genética versus biomecânica
Síndrome transicional de la columna lumbar:
teoría genética versus biomecánica
Lyonel Beaulieu Lalane1
Karen A. Weissmann Marcuson2
ABSTRACT
resumo
resumen
KEYWORDS: Intervertebral
disc/pathology; Lumbar
vertebrae/surgery; transitional
syndrome; Spinal fusion/
adverse effects
descritores: Disco
intervertebral/patologia;
Vértebras lombares/cirurgia;
Fusão vertebral/efeitos
adversos
descriptores: Disco
intervertebral/patología;
Vértebras lumbares/cirugía;
Fusión vertebral/efectos
adversos
Adjacent segment disease has been
considered a late complication of
spinal fusion. It’s described as any
degeneration that develops at mobile
segments above or below a fused
spinal segment. Several questions
have arisen in the late years regarding
this syndrome, we try to define it,
describe it and determine if it’s
caused by strain forces due to spinal
arthrodesis or whether it’s the natural
history of the degenerative spinal
process. Possibilities on conservative
and surgical management are
discussed. Spinal degeneration is a
pre – determined genetic process and
therefore the involvement of unfused
levels is an expected result.
A doença do disco adjacente tem sido
considerada como complicação tardia
da cirurgia de artrodese vertebral. Ela
é descrita como qualquer degeneração
que ocorre nos segmentos móveis acima ou abaixo do segmento vertebral
que passou pela cirurgia de artrodese.
Muitos questionamentos têm sido apresentados nos últimos anos relacionados
a esse problema e será apresentada e
discutida a possível etiologia mecânica relacionada à realização da artrodese vertebral ou ao processo degenerativo vertebral do disco intervertebral.
As possibilidades do tratamento conservador e cirúrgico são apresentadas
e discutidas. A degeneração do disco
intervertebral está relacionada à predisposição genética e o acometimento
dos segmentos vertebrais que não sofreram cirurgia de artrodese é um acontecimento esperado.
La enfermedad del disco adyacente ha
sido considerada como una complicación tardía de la artrodesis vertebral.
Ella es descrita como cualquier degeneración que ocurre en los segmentos
movibles encima o abajo del segmento vertebral artrodesados. Muchas
controversias se han presentado en
los últimos años relacionados con ese
problema. De esta forma será presentado y discutido la posible etiología
mecánica relacionada con la formación de artrodesis vertebral y el proceso degenerativo vertebral del disco
intervertebral. Las posibilidades del
tratamiento conservador y quirúrgico serán presentadas y discutidas. La
degeneración del disco intervertebral
está relacionada con la predisposición genética, con la agresión de los
segmentos vertebrales no artrodesados y una agresión esperada.
Trabajo hecho no Hospital Exequeil Gonzalez Cortés e Fundación Médica San Cristoba. Santiago, Chile.
MD, Instituto Traumatologico de Santiago, Chief of Spine group. Fundación Médica San Cristobal, member of the spine group. Member of the Sociedad Chilena
de Ortopedia y Traumatología. Santiago, Chile.
2
MD, Hospital Exequeil Gonzalez Cortés, Staff member of the spine group. Fundación Médica San Cristoba. Santiago, Chile.
1
Recebido: 19/06/08 Aprovado: 30/09/08
COLUNA/COLUMNA. 2008;7(3)276-280
Adjacent segment disease of the lumbar spine: genetic versus biomechanical theories
iNtroduction
Lumbar fusion is a procedure that has been in development for
more than 80 years. Adjacent segment disease or transitional
syndrome has been considered a late complication of spine
fusion, especially instrumented fusion. Not since the introduction
of pedicle screw fixation, a device which allows a better control
of intersegment mobility and higher load resistance, has this
syndrome been an object of real study (Figure 1).
A big metha – analysis of 101 articles documented 94.8%
fusion rates in 5756 patients studied. In relation to pedicle screw
fixation they described 12.5% rates of complications in which
adjacent segment degeneration was included1. The incidence of
this syndrome is low during the early years after surgery, but
it progressively begins to increase in frequency during the late
ones. It ranges in the lumbar spine between 5.6% at 2 years
follow-up2 to 45% at 33 years after surgery3. No all patients are
symptomatic. Actually most of findings are just X- rays ones at
follow – up. Those patients that appear symptomatic may require
surgery. In a study by Abla et al. 501 fusions in a period of 5
years, 8.2% required an extension of the original fusion, having
the time between their first and second surgery an average of 16.4
years4. Can we consider these degenerative changes as being
caused or triggered by surgery? Is the transitional syndrome
a late complication of surgery, or is the normal degenerative
process of the spine following its course? Is it natural History?
Figure 1
Adjacent segment degeneration in a 55 year old female after
a posterior fusion due to spinal stenosis. One year post-op
277
to allow its mobile segments to function normally. We know the
degenerative process is the normal ageing progression of the
spine. So how can we help not compromise the biomechanics
of an already dysfunctional spine whose mechanics are already
altered, hence the need for the original surgery anyhow. So
can we state that this process is caused by our surgery in the
opposite of it being triggered by it?
Findings at an adjacent level disease
We divided these findings in four main groups:
disc degeneration, instability, stenosis and fracture.
Disc degeneration can manifest itself as loss of disc height, disc
space narrowing6 or herniated nucleus pulposus5 (Figure 2).
Instability may be considered hipermobility of the segment
or listhesis, a 7% incidence has been reported of adjacent
instability after 2.4 years7 and 45% after 33 years2, Chen et al.
define instability of the adjacent segment as a slippage of more
than 4mm, either anterior or posterior and/or an angle change of
more than 10° on flexion and extension8. Lateral listhesis is not
mentioned in his definition, we consider it to be a component
or manifestation of instability, no studies have stated a
measurable parameter, it presence is in itself diagnostic. The
motion segment above the fused level is the most commonly
affected7-8. May be due to hypertrophic facet arthritis, Flavum
Ligament hypertrophy and/or osteophyte formation5. Fractures
are rare, but may be present as either a vertebral compression
fracture9 or a stress fracture of the pars interarticularis on both
sides10. Any of this findings by itself or combined constitute
part of the adjacent segment syndrome.
Risk factors that induce or trigger changes in the adjacent
mobile segments are plentiful. It has been mentioned adjacent facet
injury, long arthrodesis, sagittal alignment, coronal alignement,
previously degenerated segments, lumbar stenosis, PLIF, age,
osteoporosis, smoking, females and post-menopausic states5. Facet
violation is not uncommon. Astudy by Shah et al. of 212 top-level
screws where evaluation by computed tomography scan, violation
occurred in 32% of the patients with a 20% of facet involvement.
This may raise the subject of adjacent instability in those patients in
Definition
How could we define adjacent segment disease? Park et
al. describes it as any degeneration that develops at mobile
segments above or below a fused spinal segment5. We define
it as any radiological changes developing at an adjacent
segment, not necessarily immediately next to a previously
fused level at least a year after spinal fusion. These findings are
not necessarily symptomatic. However a time component has
been stated in our definition. We cannot consider alterations
at an adjacent level as a new pathology or complication, most
probably below that time lapse, those findings were already
there, a year is somewhat arbitrary, just the time it takes you not
to consider it a failed back surgery syndrome. If we believe it to
be a late complication of our surgery, then it was, maybe, our
failure to maintain the basic biomechanics of the spine in order
Figure 2
Disc narrowing, disc herniation, hipermobility found
adjacent to a previously
fused segment. Risk factors
for adjacent segment
degeneration
COLUNA/COLUMNA. 2008;7(3)276-280
Lalane LB, Marcuson KAW
278
whom facet damage was present11. Instrumented arthrodesis have
higher incidences of transitional syndromes than non instrumented
ones, a study with computed tomography showed that the facet
violation with pedicle screws is around a 30%11, in the literature one
can find in studies up to 50%, therefore this would contribute to
the acceleration of a degenerative process but secondary to facet
injury, not due to stress forces. Other studies argue against this issue
but no serious studies have been made to prove why unistrumented
arthrodesis has lesser incidences of transitional syndrome.
The length of the arthrodesis is a subject to be treated separately
as is commonly blamed. Some studies suggest that the posterior
ligamentary complex is important in maintaining the stability in
the non fused segments in relation to the fused ones12. Out of 31
patients that underwent lumbar arthrodesis with pedicular screws
in which the indemnity of the posterior ligamentary complex was
maintained only two developed adjacent segment disease over
the fused segments in comparison with 24% of the ones where
the ligamentary complex was not preserved. Out of the caudal
segments none of the patients with ligamentary complex indemnity
developed any degenerative changes in relation to 5.6% in which
it was not preserved12. The effect of PLIF was studied on adjacent
segment changes, no correlation was found between radiological
degeneration and clinical results, no risk factor were determined,
only it was suspected that the horizontalization of the lamina
and the facet tropism were one of the risk factors for secondary
neurological deterioration in the adjacent segment13. Aging people
have segment degeneration as a base, will see that this really does
not explain the pathology, this people also have absence of other
support structures, osteoporosis, especially in post – menopausal
patients and they have little physical activity which also helps
instability7. This is the core of genetic theory, that is why older
patients are more prone to develop adjacent instability and why
our interventions should be to stimulate spine stability through
physiotherapy and exercise, we may prevent in a small percentage
its development but not avoid it altogether.
Segments above or below a previous fusion
In 1950 Kellgren and Lawrence described that 50% of the population
would develop degenerative changes by the age of 504. What is it
that triggers increased changes in the segments above or below a
fusion and why it that cranial segments are affected more often is?
Studies performed both in dogs and human cadaveric specimens
show increased mobility in the adjacent segments5,14, Chow et al.
described that adjacent segments to fused ones must work more
frequently towards the extremes of their functional ranges of
motion15 especially after a multilevel fusion, therefore there is a
transference of motion from the fused segments to the free ones that
overload them. Cunningham et al.16 also described that there is a
considerable increase of up to 45% in the intradiscal pressure of
adjacent disc segment, the torque produced at the segment above is
greater than the one below, and therefore this transfer of movement
and load affect primarily the cranial one.
Immediately next to and adjacent fused
segment or supradjacent to it
Transitional syndrome usually develops in the immediately next
to a fusion. Instability requiring surgical stabilization commonly
COLUNA/COLUMNA. 2008;7(3)276-280
develops in spine’s most mobiles segments. Therefore it’s expected
that this same process develops in the levels around fusion, it’s
impossible to determine whether the symptomatic changes
that develop in a patient were due to the natural progression of
degenerative changes or induced by fusion17. A short term study
was developed at two years follow-up, where adjacent segments
were studied with magnetic resonance, important degenerative
changes in the immediately adjacent segments in relation to remote
segments were present in up to 75% of the patients18 (Figure3).
Figure 3
Supraadjacent segment
disease in a 75 - years
woman, 10 years after
surgery. Notice how the
immediately adjacent
segment remains
perfectly normal, while
the supraadjacent disc
has undergone severe
degenerative changes
Genetic versus biomechanical theories
Fifty percent % of the population develops degenerative
changes by the age of 5019, if a patient underwent surgery for
spondylotic changes in a segment; the highest probability is that
they develop the same pathology in the adjacent segments6. The
radiological changes in the transition zones in asymptomatic
fusions at ten years have the same frequency as the changes
observed in control patients that haven’t undergone surgery20.
However there is the feeling that the mechanical stress under
which the immediately adjacent segment to an arthrodesis are
submitted, suffer an accelerated degenerative process20. From
a biochemical perspective Cole found considerable changes in
the metabolism and composition of the adjacent disc to a fused
segment21-22.
Has adjacent segment disease a short or long
termed etiology
As previously mentioned, degenerative changes may appear
as early as two years after the intervention19. We defined the
presence of adjacent segment disease after a year of surgery,
but if we believe in the genetic theory, those changes being the
normal progression can either be there before surgery or evolve
rapidly after it independent on time. As age is a prognosis factor
for its development, older patients should be more predisposed
to early and higher rates of segment instability. So though Abla
et al. report 16 years average appearance of these changes4,
earlier changes are not to be excluded.
Traumatic versus degenerative etiologies to
transitional syndrome
If degenerative changes were due to overstress in adjacent
segments, then there would be no difference in the incidence
between traumatic or degenerative surgery, however this
is not the case, traumatic surgery has very little incidence
of transitional syndrome in comparison to degenerative
surgery, this mainly supports a degenerative surgery over a
biomechanical one.
Adjacent segment disease of the lumbar spine: genetic versus biomechanical theories
Previously engaged levels versus healthy ones
in adjacent degeneration
It’s reasonable to consider that a previously degenerated disc is
prone to develop adjacent instability faster than a healthy level,
even if this last one is submitted to shear stress forces. The
biomechanical theory considers that the stress forces applied to the
unfused disc are higher with more fused segments, due to a longer
lever effect; healthy disc should be more resilent to this effect.
Throckmorton et al. did a retrospective study, with a two year
follow- up were they reviewed the clinical outcomes of this two
groups, validated with the SF-36 scores and Magnetic Resonance.
Twenty patients where fused adjacent to a degenerative level, five
to a normal one, no adverse impact was detected in the adjacent
degenerated level group, with a power analysis that validated
this data with a 98% certainty, therefore it’s not a matter of stress
forces, for this are equally well tolerated in a degenerated level23.
Short versus long fusions. Does it matter?
Long fusions imply a larger lever, so they are expected to
produce more stress on the non fused segments, the longest
fusions are made in scoliosis, for those patients whose fusion
ended at L5 level a follow-up was made for up to 14 years, it
concluded that 61% of the patients developed disc degeneration
in the L5 – S1 level, this was associate with a significant
forward shift in sagital balance and revision surgery24.
We believe than more the length of the fusion is the last
level involved that matters. Rinella et al. studied the effect of
age and distal fusion levels comparing fusions ending in T11L2 to those ending L3-L4, higher rates of transition syndrome
where found in the more distal arthrodesis25.
Management
Based in the radiographic evaluations, Transitional syndrome
apparently does not correlate with a poor prognosis4. This is why
it doesn’t necessarily need a surgical treatment. Conservative
treatment may be considered with emphasis in pain control and
optimizing quality of life. In order to consider surgery we must
consider that the problem is being caused by the instability or
the secondary spinal stenosis in the lumbar spine, in the cervical
spine. Chen et al. described instability in transitional syndrome as
a listhesis of more than 4mm or an angular variation higher than
10°7-8, Schlegel et al. defined instability as a listhesis in continuity
to a fused segment or significant malalignement whether in the
coronal or sagittal plane without specifying measurements26. What
consideration should we take when we think surgery, we should
asses what kind of involvement there is in order to chose the best
treatment, is there compression or instability. How many levels
are involved and how long was the previous arthrodesis, which
was the last level fused and what option do we have of extending
this fusion, of course things we must consider for any patient are
age, bone quality and co morbidities. And of course we must never
forget to try and explain the physiopathology of the disease, why
did this happen and how could I have avoided it.
In order to solve the problem we have three alternatives,
decompression without fusion, arthrodesis whether instrumented or
not and in the future we might consider using a disc arthoplasty. We
can consider only decompressing in those patients with no proven
279
instability, in the presence of a single unilateral radiculopathy,
lateral disc herniations or single level foraminal stenosis due to
osteophyte formation. This would be the minimal useful surgery
we could offer a patient, its advantages are a shorter surgical time
and therefore the co morbidities associated and the preservation
of the segment mobility, however we cannot predict whether
instability will develop in the segment after laminoforaminotomy4.
It would be mandatory to respect the respective facets, eventual
fusion may occur. To approach the patient considering fusion
without instrumentation is a mistake, Whitecloud et al. observed
an 80% of non union in non instrumented patients27.
Satisfactory results have been obtained with the instrumented
extension of fusion and decompression, the same Whitecloud et
al. saw that their rate of non-union fell to 17% with the use of
instrumented fusion27, Chen et al. reported a 5.1% of non union in
his prolonged fusion using this technique7 but adjacent segment
disease may then develop in the next adjacent level.
A new possibility is to consider the use of disc arthoplasty,
it was published a case report concerning the use of a Bryan
disc in the two altered levels above a previous fusion on the
cervico – thoracic junction, it had a good result at short term
follow-up, but we must wait and see how it actually performs28.
The down part of surgery is that this is a very complex surgery
in an already involved segment, complication described for
this surgery are persistent pain, CSF leakage, fracture of the
osteosinthesis instrumentation, non union, higher infection risk,
excessive blood loss and higher risk of neurological damage5.
There is evidence that the percentage of complications
is higher in patients that require fusion of multiple segments
as opposed to those that only require a one level fusion4. The
outcome of surgery is not good, Park et al. considered that post
– operative pain is the only predictor of a poor result in patients
submitted to decompression by a transitional syndrome5, but
Abla et al. observed that the affectivity of surgery is 30 to 70%
in different series, other than pain, other aetiologies for failed
back surgery syndrome must be under consideration4.
Medicine is moving towards prevention more than treatment,
so how could we prevent transitional syndrome. If we favour
the degenerative theory, the only solution we might offer our
patient is gene therapy to treat any predetermined degenerative
changes, this is still under research and as yet nothing has been
proved concerning this matter. If we go with the biomechanical
theory there are some things we could do, dynamic stabilization,
whether with disc arthroplasty or dynamic instrumentation is an
option. Guyer et al. published 63 to 85% of good results with disc
arthoplasty, however for the moments indications are limited29,
An 8.6 year follow-up (7 to 10 years) of “ProDisc I” showed a
26% of transitional syndrome at 34 studied levels30, so under a
degenerative perspective arthroplasty does not prevent adjacent
instability, under a biomechanical perspective, disc arthoplasty
does not modify degenerative changes of the posterior spinal
complex, where degenerative disease may begin either in the
operated segment or the ones adjacent to it.
However the presence of a disc does not interfere with
intradiscal pressure in the segments above it, a study by Dmitriev et
al. was performed in the cervical spine it was a human in vitro study
of 10 cadavers concerning the C5- C6 junction, the bodies where
COLUNA/COLUMNA. 2008;7(3)276-280
Lalane LB, Marcuson KAW
280
classified as either control, undergoing disc arthoplasty, allograft and
plating plus allograft, the spines where submitted to axial rotation,
flexo-extension and bending. The intradiscal pressure was not
altered in either the arthoplasty or the control groups, this was most
significant in flexo-extension where fused subjects had significantly
higher intradiscal pressure than both the arthoplasty and control
group. Range of movement though less than the control group was
maintained in the arthoplasty group30. Perhaps the absence of strain
in the adjacent segments will somehow prevent adjacent segment
disease, there is not enough follow up to conclude either way.
Hashimoto et al. compared the incidence at five years
follow-up of adjacent segmented disease and revision surgery
in posterolateral fusion and those fused with the artificial
Graf ligament. At the first group between 25 and 43% of the
patients where affected, of those 18.5% required surgery, in the
second group six to 18% presented adjacent instability and of
those 5.6% required revision surgery32. So there is a degree of
prevention in dynamic stabilizations. Sengupta et al. published
19% of revision surgery with the use of dynamic stabilization33,
this would avoid the strain over the above segment but wouldn’t
prevent the natural history of the pathology.
REFERENCES
1. Dickman CA, Yahiro MA, Lu HT,
Melkerson MN. Surgical treatment
alternatives for fixation of unstable
fractures of the thoracic and lumbar spine.
A meta-analysis. Spine. 1994; 19(20
Suppl):2266S-2273S.
2. Kuslich SD, Danielson G, Dowdle JD,
Sherman J, Fredrickson B, Yuan H,
Griffith SL. Four-year follow-up results of
lumbar spine arthrodesis using the Bagby
and Kuslich lumbar fusion cage. Spine.
2000; 25(20):2656-62.
3. Lehmann TR, Spratt KF, Tozzi JE,
Weinstein JN, Reinarz SJ, el-Khoury GY,
Colby H. Long-term follow-up of lower
lumbar fusion patients. Spine. 1987;
12(2):97-104.
4. Abla AA, El Kadi H, Bost J, Maroon JC,
Wert M, Abla A. Degenerative changes
above and below lumbar fusion. Contemp
Spine Surg. 2006;7(2):1-5.
5. Park P, Garton HJ, Gala VC, Hoff JT,
McGillicuddy JE. Adjacent segment
disease after lumbar or lumbosacral fusion
: review of the literature. Spine. 2004;
29(17): 1938-44. Review.
6. Miyakoshi N, Abe E, Shimada Y,
Okuyama K, Suzuki T, Sato K. Outcome
of one-level posterior interbody fusion
for spondylolisthesis and postoperative
intervertebral disc degeneration adjacent to
the fusion. Spine. 2000; 25(14):1837-42.
7. Chen WJ, Lai PL, Niu CC, Chen LH,
Fu TS, Wong CB. Surgical treatment of
adjacent instability after lumbar spine
fusion. Spine. 2001; 26(22):E519-24.
8. Chen WJ, Lai PL, Chen LH. Adjacent
instability after instrumented lumbar
fusion. Chang Gung Med J. 2003;
26(11):792-8.
COLUNA/COLUMNA. 2008;7(3)276-280
Conclusion
Adjacent segment disease is a difficult and controversial
pathology, its diagnosis and treatment are complicated
and unfortunately it seems we cannot yet prevent it.
However we do not consider it as previously described a
late complication of spine fusion. Most of the literature
reviewed support that degenerative changes are already
present or developing when we decide to fix a segment.
Seventy five percent (75%) of degenerative changes at
mobile segments at only two years follow up are described,
despite the average 16 years in the development of adjacent
instability. So we cannot blame stress forces for what nature
is responsible. Adjacent segment degeneration is the natural
progression of the patient’s spine, we believe that with our
interference we trigger or accelerate the process but we
do not produce it, that is why dynamic stabilization aids
in diminishing the probability of transitional syndrome, it
does not eliminate it. When we figure out how to stop,
avoid or treat the normal degenerative process, aging as
we more commonly know it, we will prevent this disease.
Gene therapy is our next step.
9. Etebar S, Cahill DW. Risk factors for
adjacent-segment failure following
lumbar fixation with rigid instrumentation
for degenerative instability. J Neurosurg.
1999; 90(2 Suppl):163-9.
10.Brunet JA, Wiley LJ. Acquired
spondylolysis after spinal fusion. J
Bone Joint Surg Br. 1984; 66(5):720-4.
11.Shah RR, Mohammed S, Saifuddin A,
Taylor BA. Radiologic evaluation of
adjacent superior segment facet joint
violation following transpedicular
instrumentation of the lumbar spine.
Spine. 2003; 28(3):272-5.
12.Lai PL, Chen LH, Niu CC, Fu
TS, Chen WJ. Relation between
laminectomy and development of
adjacent segment instability after
lumbar fusion with pedicle fixation.
Spine. 2004; 29(22):2527-32;
discussion 2532.
13.Okuda S, Iwasaki M, Miyauchi A, Aono
H, Morita M, Yamamoto T. l Risk factors
for adjacent segment degeneration after
PLIF. Spine. 2004; 29(14): 1535-40.
14.Bastian L, Lange U, Knop C, Tusch
G, Blauth M. Evaluation of the
mobility of adjacent segments after
posterior thoracolumbar fixation: a
biomechanical study. Eur Spine J.
2001; 10(4):295-300.
15.C how DH, Luk KD, Evans
JH, Leong JC. Effects of short
anterior lumbar interbody fusion
on biomechanics of neighboring
unfused segments. Spine. 1996;
21(5):549-55.
16.Cunningham BW, Kotani Y, McNulty
PS, Cappuccino A, McAfee PC. The
effect of spinal destabilization and
instrumentation on lumbar intradiscal
pressure: an in vitro biomechanical analysis.
Spine. 1997; 22(22):2655-63.
17.Emery SE, Bohlman HH, Bolesta MJ, Jones PK.
Anterior cervical decompression and arthrodesis
for the treatment of cervical spondylotic
myelopathy. Two to seventeen-year follow-up. J
Bone Joint Surg Am. 1998; 80(7):941-51.
18.Kulkarni V, Rajshekhar V, Raghuram L.
Accelerated spondylotic changes adjacent to
the fused segment following central cervical
corpectomy: magnetic resonance imaging
study evidence. J Neurosurg. 2004;100(1
Suppl Spine):2-6. Comment in: J Neurosurg.
2004; 100(1 Suppl Spine):1; discussion 1.
19.Kellgren JH, Lawrence JS. Osteo-arthrosis and
disc degeneration in an urban population. Ann
Rheum Dis. 1958;17(4):388-97.
20.Hambly MF, Wiltse LL, Raghavan N,
Schneiderman G, Koenig C. The transition
zone above a lumbosacral fusion. Spine. 1998;
23(16):1785-92.
21.Cole TC, Burkhardt D, Ghosh P, Ryan M,
Taylor T. Effects of spinal fusion on the
proteoglycans of the canine intervertebral disc.
J Orthop Res. 1985; 3(3):277-91.
22.Cole TC, Ghosh P, Hannan NJ, Taylor TK,
Bellenger CR. The response of the canine
intervertebral disc to immobilization produced by
spinal arthrodesis is dependent on constitutional
factors. J Orthop Res. 1987; 5(3):337-47.
Correspondência
Lyonel Beaulieu Lalane
Luis Pasteur 5292, Vitacura, Santiago,
Chile
Tel.: + 56-2 7549500
E-mail: [email protected]
[email protected]