DOI:10.2214/AJR.07.3550
AJR 2008; 191:115-123
© American Roentgen Ray Society
Correlation of MRI-Based Bone Marrow Burden Score with Genotype and Spleen Status in Gaucher's Disease
Robert F. DeMayo1,2,
Andrew H. Haims1,
Matthew C. McRae1,
Ruhua Yang3 and
Pramod K. Mistry3
1 Department of Radiology, Yale University School of Medicine, 333 Cedar St., PO
Box 208042, New Haven, CT 06520-8042.
2 Present address: Oregon Health & Science University, Portland, OR
97239.
3 Section of Pediatric Hepatology and Gastroenterology, Yale University School
of Medicine, New Haven, CT.
Received December 15, 2007;
accepted after revision January 23, 2008.
Address correspondence to A. H. Haims
(Andrew.Haims{at}Yale.edu).
Abstract
OBJECTIVE. The purpose of this study was to correlate skeletal
pathologic findings quantified by MRI-based bone marrow burden score with
genotype and spleen status and other clinical parameters, including liver size
and duration of enzyme replacement therapy, in patients with Gaucher's
disease.
MATERIALS AND METHODS. Two radiologists retrospectively reviewed MR
images of 47 patients with Gaucher's disease and determined bone marrow burden
scores by consensus on the basis of previously published criteria. The bone
marrow burden scores were correlated with genotype, liver volume, spleen
status, age, and cumulative duration of enzyme replacement therapy.
RESULTS. Subjects with compound heterozygous N370S alleles
had significantly higher overall, lumbar spinal, and femoral bone marrow
burden scores than did N370S homozygotes. There was a significant
positive correlation between an enlarged or surgically absent spleen and bone
marrow burden score. There were no significant associations between bone
marrow burden score and liver volume, age, cumulative duration of enzyme
replacement therapy, or cumulative duration of untreated disease. Femoral and
lumbar spinal bone marrow burden scores had a weak but significant positive
correlation across all patients.
CONCLUSION. Skeletal pathologic findings in Gaucher's disease
encapsulated as bone marrow burden score correlate significantly with the
number of copies of the N370S allele, which has an ameliorative
effect on bone marrow disease. Splenectomy or splenomegaly is associated with
greater risk of bone marrow disease. Femoral and lumbar spinal bone marrow
burden scores, although only weakly correlated, independently illustrated both
the protective role of the N370S allele and the unfavourable implication of
splenectomy. This finding suggests that axial and appendicular bone marrow
burdens are related but distinct and justifies multiple-compartment evaluation
in Gaucher's disease.
Keywords: bone marrow burden score • Gaucher's disease • MRI
Introduction
Gaucher's disease (GD), the most common lysosomal storage disorder, is
caused by deficiency of the enzyme β-glucocerebrosidase. Accumulation of
glucocerebroside in the liver, spleen, and bone marrow results in the clinical
manifestations of hepatosplenomegaly, anemia, thrombocytopenia, bone pain, and
skeletal disability. In nonneuron opathic GD, skeletal manifest ations usually
produce the greatest morbidity and long-term disability, causing serious
complications, such as osteonecrosis and pathologic fractures, in more than
50% of patients
[1–3].
Genetic factors play an important but not determinative role in the
development of skeletal involvement in GD. Among patients of Ashkenazi Jewish
descent, the four mutations N370S, 84GG, L444P, and IVS2+1
account for at least 90% of cases of symptomatic GD
[4]. In the United States, most
patients have at least one copy of the N370S allele
[5]. Homozygosity for
N370S is associated with a milder phenotype, and a single copy of the
N370S allele is considered protective against neuronopathic disease
[6]. In contrast, the
L444P mutation has been associated with a more disabling course,
including neuronopathic manifestations and severe skeletal involvement
[7].
Enzyme replacement therapy with purified macrophage-targeted human
β-glucocerebrosidase has been shown to arrest or reverse the biochemical,
hematologic, visceral, and skeletal abnormalities of GD
[8–10].
Although many bone lesions respond to enzyme replacement therapy,
osteonecrosis, osteosclerosis, and vertebral compression are generally
irreversible [4,
11]. In the era of enzyme
replacement therapy, sensitive assess ment and monitoring of skeletal disease
are critical to timely intervention before perma nent disability is incurred
[4]. Quantitative MRI-based
methods have been developed to measure bone marrow infiltration in GD. The
most promising is Dixon quantitative chemical shift imaging (QCSI)
[12]. Results of QCSI of the
lumbar spine are reproducible
[13], correlate with disease
activity as in dicated by spleen size
[14], and are sensitive for
bone marrow response to enzyme replace ment therapy
[9]. Despite these advan tages,
QCSI is available at only a few academic centers worldwide and thus is not a
realistic option in most clinical settings.
Because of the practical limitations of QCSI, multiple semiquantitative
approaches to bone marrow disease in GD have been developed, including a
variety of scoring systems based on predictable changes in MR signal intensity
and anatomic distribution
[15]. The characteristic
progression of disease within the femur, from proximal metaphysis to diaphysis
to proximal and then distal epiphysis, has been the principal, if not the
sole, criterion on which most previously reported scoring systems have been
based. Reflecting this bias, in current published imaging guidelines
[4] and actual clinical
practice, MRI evaluation of skeletal disease in GD is often limited to the
femurs. Maas and colleagues
[16] proposed an alternative
bone marrow burden scoring system that in corpo rates signal intensity and
distribution para meters for the lumbar spine in addition to the femurs. In an
investigation in which the subjects were 30 patients with previously untreated
GD, Maas et al. found promising features of the bone marrow burden in terms of
reproducibility, correlation with QCSI findings, and sensitivity as an
indicator of response to enzyme replacement therapy.
In this study, we sought to apply the bone marrow burden scoring system to
a large, unselected group of patients with GD and to explore correlations
between bone marrow burden score and genotype and additional clinical
parameters, such as liver volume, spleen status, age, cumulative duration of
enzyme replacement therapy, and cumulative duration of untreated disease.
Materials and Methods
Subjects
The study was approved by the institutional human investigation committee,
which waived the requirement for informed consent, and was compliant with the
HIPAA. The study was performed at a university hospital that is a regional
referral center for GD. A computer search of the institutional imaging report
database was per formed to identify patients with GD who under went MRI of the
lumbar spine and femurs between January 2002 and March 2006. All available
corresponding medical records were reviewed for clinical parameters of
interest. Patients were retrospectively included in the study if simultaneous
sagittal T1-weighted and STIR images (or, in the case of two patients,
fat-suppressed T2-weighted images) of the lumbar spine and coronal T1-weighted
and STIR images of the femurs were available; liver and spleen volumes had
been calculated on the basis of findings on concurrent volumetric MRI of the
abdomen; genotype analysis had been performed; and a history of enzyme
replacement therapy was available, including the date of initiation and the
chronology of regimen changes. Patients younger than 18 years were excluded
from the study to minimize the confounding effect of hematopoietic bone
marrow. In this review, 47 patients with GD were identified and formed the
study population.
Imaging Protocol
All patients underwent MRI of the lumbar spine and both femurs with a 1.5-T
system. Lumbar spinal imaging was performed with a phased-array spine coil and
consisted of a sagittal T1-weighted sequence (TR/TE, 600/13; bandwidth, 15.63
kHz; matrix size, 512 x 256; number of signals averaged, 2; field of
view, 28 cm2; spacing, 4:1 mm) and a sagittal fast spin-echo STIR
sequence (2,925/60; inversion time, 140 milliseconds; echo-train length, 8;
bandwidth, 15.63 kHz; matrix size, 256 x 192; number of signals
averaged, 4; field of view, 28 cm2; spacing, 4:1 mm). For two
patients, a sagittal fat-suppressed fast spin-echo T2-weighted sequence with
parameters similar to those of the other sequences was used instead of the
STIR sequence. Femoral imaging was performed with a phased-array torso coil
and consisted of a coronal T1-weighted sequence (725/14; bandwidth, 15.63 kHz;
matrix size, 256 x 160; number of signals averaged, 1; field of view, 36
cm2; spacing, 4:1 mm) and a coronal fast spin-echo STIR sequence
(7,250/ 60; inversion time, 140 milliseconds; echo-train length, 8; bandwidth,
31.25 kHz; matrix size, 256 x 224; number of signals averaged, 2; field
of view, 36 cm2; spacing, 4:1 mm).
Bone Marrow Burden Evaluation
Two radiologists with 10 and 3 years of experience analyzed all MR images
and assigned bone marrow burden scores by consensus. Both readers were blinded
to clinical parameters. Bone marrow burden scores at each anatomic location
were based on signal intensity and distribution according to a modified
version of previously published criteria
[16] (Tables
1 and
2) and ranged from 0 to 8 for
the lumbar spine (Figs. 1,
2,
3,
4A,
4B) and from 0 to 8 for the
femurs (Figs. 5A,
5B,
6A,
6B,
7A,
7B), for an overall score of
0–16. For determining the femoral site of involvement, hip or knee
replace ment was interpreted as evidence of proximal or distal femoral
epiphyseal disease. In all equivocal cases, scoring was performed according to
a worst-case standard.
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Fig. 1 —28-year-old woman with Gaucher's disease. Sagittal
T1-weighted MR image shows normal bone marrow signal intensity is high in
relation to nondiseased intervertebral disk signal intensity. Findings on STIR
image (not shown) also were normal. Bone marrow burden score is 0.
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Fig. 2 —32-year-old woman with Gaucher's disease. Sagittal
T1-weighted MR image shows patchy bone marrow infiltration, which is
hypointense in relation to nondiseased intervertebral disk signal intensity
with preservation of fat around basivertebral vein. Findings on STIR image
were normal (not shown). Bone marrow burden score is 4 (3 for intensity, 1 for
distribution).
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Fig. 3 —55-year-old woman with Gaucher's disease. Sagittal
T1-weighted MR image shows slightly hypointense bone marrow signal in diffuse
distribution with absence of fat around basivertebral vein. Findings on STIR
image were normal (not shown). Bone marrow burden score is 5 (2 for intensity,
3 for distribution).
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Fig. 4A —49-year-old man with Gaucher's disease. Sagittal T1-weighted
(A) and STIR (B) MR images show bone marrow infiltration,
infarction, and fractures. Patchy area of low signal intensity is evident in
A, as are absence of fat around basivertebral vein and high signal
intensity in B. Bone marrow burden score is 7 (5 for intensity, 2 for
distribution).
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Fig. 4B —49-year-old man with Gaucher's disease. Sagittal T1-weighted
(A) and STIR (B) MR images show bone marrow infiltration,
infarction, and fractures. Patchy area of low signal intensity is evident in
A, as are absence of fat around basivertebral vein and high signal
intensity in B. Bone marrow burden score is 7 (5 for intensity, 2 for
distribution).
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Fig. 5A —41-year-old man with Gaucher's disease. Coronal T1-weighted
(A) and STIR (B) MR images show minimal bone marrow infiltration
with slightly low (A) and slightly high (B) signal intensity in
both femurs with diaphyseal distribution. Bone marrow burden score is 3 (2 for
intensity, 1 for distribution).
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Fig. 5B —41-year-old man with Gaucher's disease. Coronal T1-weighted
(A) and STIR (B) MR images show minimal bone marrow infiltration
with slightly low (A) and slightly high (B) signal intensity in
both femurs with diaphyseal distribution. Bone marrow burden score is 3 (2 for
intensity, 1 for distribution).
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Fig. 6A —70-year-old man with Gaucher's disease. Coronal T1-weighted
(A) and STIR (B) MR images show low (A) and high
(B) signal intensity in diaphyseal distribution in right femur. Bone
marrow burden score is 5 (4 for intensity, 1 for distribution).
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Fig. 6B —70-year-old man with Gaucher's disease. Coronal T1-weighted
(A) and STIR (B) MR images show low (A) and high
(B) signal intensity in diaphyseal distribution in right femur. Bone
marrow burden score is 5 (4 for intensity, 1 for distribution).
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Fig. 7A —41-year-old woman with Gaucher's disease. Coronal T1-weighted
(A) and STIR (B) MR images show low (A) and high
(B) signal intensity in diaphyseal distribution in left femur. Bone
marrow burden score is 6 (5 for intensity, 1 for distribution).
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Fig. 7B —41-year-old woman with Gaucher's disease. Coronal T1-weighted
(A) and STIR (B) MR images show low (A) and high
(B) signal intensity in diaphyseal distribution in left femur. Bone
marrow burden score is 6 (5 for intensity, 1 for distribution).
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Clinical Data
Clinical data acquisition was conducted by one author and included patient
age and sex, genotype, liver and spleen volumes (calculated from concurrent
findings on volumetric MRI of the abdomen), history of splenectomy, and
details of enzyme replacement therapy (date of initiation and chronology of
regimen changes). Because all patients had at least one copy of the
N370S allele, for primary data analysis, genotype was classified as
N370S homozygous and N370S compound heterozygous. Because
nearly one half (20 of 47) of the patients had undergone splenectomy, spleen
status was treated as a categoric variable, with a value of 0 for spleen size
within the range of normal, 1 for an enlarged spleen (> 200 cm2
in diameter), and 2 for a surgically absent spleen. Regarding the statistical
analysis of enzyme replacement therapy, both the cumulative duration of
therapy and the cumulative duration of untreated disease (defined as age minus
cumulative duration of enzyme replacement therapy) were considered.
Statistical Analysis
Data were analyzed with SAS software (version 9.1, SAS). Differences
between groups were analyzed with the nonparametric Wilcoxon's test.
Correlation was calculated with two-tailed nonparametric Spearman's rank
correlation (
). A value of p < 0.05 was considered
significant.
Results
The clinical information and imaging data are summarized in
Table 3. The study population
consisted of 47 patients (27 women, 20 men; mean age, 44.6 years; range,
18–71 years). All patients had at least one copy of the N370S
allele. Nineteen (40%) of the patients were homozygous for N370S, and
28 (60%) were compound heterozygous with one N370S allele and one
other mutant allele. Genotypes in the heterozygous group were distributed as
follows: eight patients (17% of total study population) with
N370S/L444P, seven (15%) with N370S/84GG,
six (13%) with N370S/IVS+2, five (11%) with
N370S/? (the question mark denoting an uncharacterized
mutant allele), and one (2%) each with N370S/R131L and
N370S/V394L. Thirty-seven (79%) of the 47 patients were
undergoing enzyme replacement therapy. The homozygous and heterozygous groups
each included five patients with previously untreated disease. The homozygous
and compound heterozygous groups did not differ significantly in age
distribution, cumulative duration of enzyme replacement therapy, or cumulative
duration of untreated disease. There were, however, significantly more women
in the homozygous group (79%, 15 of 19) than in the heterozygous group (43%,
12 of 28) (p = 0.02).
Compound heterozygotes had more severe skeletal disease than did
homozygotes, having higher overall bone marrow burden scores (p <
0.001), lumbar spinal bone marrow burden scores (p < 0.01), and
femoral bone marrow burden scores (p < 0.01)
(Table 4,
Fig. 8). Within the homozygous
group, overall bone marrow burden scores ranged from 0 to 15 (median, 6),
lumbar spinal bone marrow burden scores from 0 to 8 (median, 3), and femoral
bone marrow burden scores from 0 to 8 (median, 3). Within the heterozygous
group, overall bone marrow burden scores ranged from 2 to 16 (median, 10),
lumbar spinal bone marrow burden scores from 0 to 8 (median, 5), and femoral
bone marrow burden scores from 2 to 8 (median, 6). Considering all genotypes
with at least five patients, N370S/ L444P was associated with the
greatest burden of skeletal disease (median overall bone marrow burden score,
11). All five patients with maximal skeletal disease (overall bone marrow
burden score, 16) were compound heterozygotes, two with
N370S//L444P and one each with N370S/84GG, N370S/?,
and N370S/R131L. Perhaps owing to the small numbers of patients,
there were no statistically significant differences in skeletal disease
between the various compound heterozygous subgroups. Femur and lumbar spine
bone marrow burden scores were weakly but significantly correlated across all
patients ( = 0.40, p < 0.01)
(Fig. 9). In subgroup
analysis, this correlation persisted for the compound heterozygotes ( =
0.43, p = 0.02) but was nonexistent among the N370S
homozygotes ( = –0.04, p = 0.87). The difference, however,
was not statistically significant (p = 0.12).
Considering all patients, there was a significant association between an
enlarged or surgically absent spleen and more severe bone marrow infiltration
in both the axial and appendicular skeletons, reflected as positive
correlations between spleen status and overall bone marrow burden score (
= 0.51, p < 0.001), lumbar spinal bone marrow burden score (
= 0.43, p < 0.01), and femoral bone marrow burden score ( =
0.42, p < 0.01) (Table
4). In subgroup analysis, there was a trend toward greater
skeletal disease with abnormal spleen status in all instances except for
femoral bone marrow burden in the N370S homozygous group. This trend,
however, was significant only for overall bone marrow burden score ( =
0.46, p = 0.01) and femoral bone marrow burden score ( = 0.47,
p = 0.01) in the compound heterozygous group.
There was a significant negative correlation between liver volume and
cumulative duration of enzyme replacement therapy across all patients ( =
–0.42, p < 0.01). This trend was also found in subgroup
analysis and was significant for homozygotes ( = –0.56, p
= 0.01) but not for compound heterozygotes ( = –0.36, p =
0.06). There were no significant associations between skeletal disease and
liver volume, age, cumulative duration of enzyme replacement therapy, or
cumulative duration of untreated disease.
Discussion
To our knowledge, this study is the first to implement bone marrow burden
scoring in an unselected group of patients with GD and to explore the relation
between bone marrow burden score and genotype. Our subjects were generally
representative of the U.S. population of patients with GD in terms of
distribution of genotypes and prevalence of enzyme replacement therapy. The
severity of bone marrow infiltration correlated significantly with genotype,
specifically with the number of copies of the N370S allele.
Homozygotes with two copies of the N370S allele had significantly
lower bone marrow burden scores than compound heterozygotes with only one copy
of the N370S allele.
Although there were no statistically significant differences between the
compound heterozygote subgroups, the N370S/L444P genotype was
associated with uniformly severe skeletal disease, two of eight patients
having the maximum possible bone marrow burden score and five of eight
patients having advanced irreversible pathologic changes in the form of having
undergone total joint replacement or having vertebral compression fractures.
Severe bone marrow burden was also generally evident in the
N370S/IVS+2 and N370S/? genotypes. The
N370S/84GG genotype exhibited substantial variability in degree of
bone marrow infiltration.
The correlation between genotype and bone marrow burden in our study was
generally concordant with published data regarding associations between
genotype and disease severity in GD. The ameliorative effect of the
N370S allele and the unfavorable effect of other mutations,
particularly L444P, are well known and appear partially attributable
to differential gluco cerebrosidase enzyme activity. For example,
Pasmanik-Chor and colleagues
[17], using a vaccinia
virus–derived system to express normal and mutated glucocerebrosidase in
human cells, found that the N370S enzyme has activity comparable with
that of its normal counterpart, whereas other mutant enzymes, in cluding
L444P and 84GG, have significantly less activity.
The relation between spleen status and bone marrow burden in our study was
in agreement with earlier observations. Patients who had undergone splenectomy
or who had splenomegaly had significantly higher bone marrow burden scores,
both in the axial and appendicular skeletons, than did those with intact,
normal-sized spleens. This finding substantiates a previously reported
[18] asso ciation between
splenectomy and skeletal lesions and supports the notion that com promise of
the splenic reservoir of GD cells accelerates progression of disease in other
compartments.
The absence of a significant correlation between enzyme replacement therapy
and bone marrow infiltration is our most striking negative finding but must be
interpreted with caution given that our primary objective was to explore the
association between genotype and skeletal disease. Enzyme replacement therapy
was at best a secondary consideration, incorporated mainly to mitigate its
potential as a confounding factor. This investigational bias is reflected in
our method, particularly its static framework, which handicapped our ability
to discern the influence of enzyme replacement therapy on bone marrow disease
over time. Numerous previous studies have shown that enzyme replacement
therapy decreases glucocerebroside accumulation and increases normal fat
content in bone marrow [11].
In the earlier studies, longitudinal data were used to explore intraindividual
rather than interindividual differences related to enzyme replacement therapy.
Future investigations incorporating longitudinal bone marrow burden data are
needed, not only to validate the sensitivity of bone marrow burden scoring as
an indicator of response to enzyme replacement therapy but also to assess the
relation between genotype and the efficacy of enzyme replacement therapy.
Femoral and lumbar spinal bone marrow burden scores correlated only weakly,
but each score independently illustrated both the protective role of the
N370S allele and the unfavorable implication of splenectomy. These
results suggest the phenotypic complexity of GD applies not only to individual
organ systems but also to the axial and appendicular compartments of the
skeleton. If, as Maas and colleagues
[16] propose, lumbar bone
marrow burden is more reflective of reversible pathologic changes but femoral
bone marrow burden is more indicative of static disease, it is natural that
these two parameters would overlap to some extent while still conveying
distinct information. The multiple-compartment approach of bone marrow burden
is an advance over previous scoring systems and highlights the limitation of
imaging protocols restricted to the femurs.
In implementing bone marrow burden scoring, we encountered a few practical
challenges that were fairly easily overcome. The Maas bone marrow burden
guidelines are based on non-fat-suppressed fast spin-echo T2-weighted
sequences instead of STIR sequences. STIR imaging is compatible with the
premise of bone marrow burden scoring because the inversion pulse affects fat
signal intensity uniformly regardless of location. However, with STIR imaging,
the femoral signal intensity categories slightly hypointense and hypointense
relative to subcutaneous fat are no longer applicable, necessitating a
modified bone marrow burden scoring system that omits these designations.
Because our methods deviated from those in the original report by Maas and
colleagues [16], neither the
reproducibility nor the validity of our bone marrow burden scores can be
assumed. Despite this limitation, we believe STIR imaging is justified because
of its superior sensitivity for bone marrow edema compared with a long-TE
sequence without fat suppression.
The bone marrow burden criteria were developed and validated for previously
untreated patients with GD, presumably with less advanced disease and a low
prevalence, if any, of joint replacement. In our study group, 10 of 47
patients had a total of 12 hip and three knee prostheses, which we interpreted
as evidence of proximal or distal femoral epiphyseal involvement. Certain
clinical scenarios in GD occur with sufficient frequency that they must be
anticipated and explicitly addressed in an optimal scoring system. We believe
joint prostheses fall into this category.
Bone marrow burden scoring is ideally suited to ranking disease as it
progresses along a predictable continuum of anatomic distribution or signal
intensity, but the pathologic process frequently deviates from its expected
trajectory or fails to fit neatly into a single category. One patient in our
study, for example, had infarction of the distal but not the proximal femoral
epiphyses. We assigned her femoral site of involvement three points,
deliberately overlooking the fact that her disease skipped a location (Fig.
10A,
10B). Because these types of
inconsistencies are inevitable in any categoric scoring system, we support
general standards for resolving them, such as the worst-case approach, to
minimize subjectivity in interpretation.
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Fig. 10A —29-year-old woman with Gaucher's disease. Coronal T1-weighted
MR image of lower part of femurs shows low signal intensity in right distal
femoral epiphysis consistent with infarction.
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Fig. 10B —29-year-old woman with Gaucher's disease. Coronal T1-weighted
MR image of upper part of femurs shows normal signal intensity in proximal
femoral epiphyses. Pattern deviates from characteristic progression of bone
marrow pathologic changes in Gaucher’s disease, in which proximal
femoral epiphyseal involvement precedes distal epiphyseal involvement.
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The bone marrow burden system does not explicitly address irreversible
pathologic skeletal changes such as infarction, osteonecrosis, and fracture, a
bias justified by its designers on the grounds that "irreversible
components would be relatively insensitive to subtle changes in bone marrow
invasion" [16].
Consequently, at times the bone marrow burden indicates the presence of
discrete, likely irreversible complications in the currency of continuous,
reversible bone marrow infiltration, giving the false impression the two
processes are, with appropriate weighting, equivalent. This approach is
exemplified by the symmetry of the point system used for T2 relaxation, in
which equal values are assigned to hypointense bone marrow infiltrated by GD
cells and to hyperintense bone marrow that may be infarcted. Chronic
irreversible change can inflate the bone marrow burden and exaggerate the
impression of reversible bone marrow in filtration, as illustrated by the four
patients in our study with a femoral score of 6 or 7 but a lumbar spinal score
of 0. All of these patients had evidence of chronic medullary infarcts in the
femurs (in three cases confirmed after review of longitudinal MRI data not
considered during bone marrow burden assessment) but no signs of reversible
bone marrow disease.
Limitations of our study included its retrospective design, relatively
small numbers of patients in each subgroup (which may account for the lack of
a clear statistical relation between bone marrow burden scores and specific
compound heterozygous subgroups), lack of verification of results against the
reference standard of Dixon QCSI, and absence of longitudinal data for
assessment of changes in bone marrow burden related to natural progression of
disease or response to enzyme replacement therapy.
The semiquantitative MRI-based bone marrow burden score indicates the
presence of marked ameliorative and adverse effects of the N370S
allele and splenectomy, respectively, on bone marrow disease in GD. Axial and
appendicular bone marrow burden scores convey related but distinct information
and should be individually evaluated. The bone marrow burden scoring system
represents an advance in terms of multiple-compartment evaluation of skeletal
disease in GD but is limited by lack of differentiation of reversible and
irreversible pathologic changes. Future investigation is needed to address
this limitation and to explore the interplay between axial and appendicular
forms of disease and between genotype and the efficacy of enzyme replacement
therapy.
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Abstract
Introduction
