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Bone mass in Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia.

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AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 80:107-113 (1989)
Bone Mass in Guamanian Patients With Amyotrophic Lateral
Sclerosis and Parkinsonism-Dementia
RALPH M. GARRUTO, CHRIS C. PLATO, RICHARD YANAGIHARA,
KATHLEEN FOX. JAMES DUTT. D. CARLETON GAJDUSEK.
AND JORDAN TOBIN
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, Maryland 20892 (R.M.G.,R.Y., D.C.G.);Applied Physiology
Section, National Institute on Aging, Francis Scott Key Medical Center,
Baltimore, Maryland 21224 (C.C.P., K.F., J.T.); Department of Computer
Science, University of South Alabama, Mobile, Alabama 36688 (5.0.)
KEY WORDS
Bone loss, ALS, PD Guam, Longitudinal study
ABSTRACT
Bone mass, as assessed by measurements of total subperiosteal diameter and medullary width of the second metacarpal bone on
hand-wrist radiographs, was evaluated for 31 Guamanian patients (15 males,
16 females) with amyotrophic lateral sclerosis (ALS),
67 patients (39 males, 28
females) with parkinsonism-dementia (PD), and 66 (34 males, 32 females)
nonaffected Guamanian controls. Comparisons between the two disease
groups and between each disease group and the nonaffected controls were
made taking into account the sex, age, and disability status ofeach participant.
At all ages, ALS patients of both sexes had significantly lower percent cortical
areas (PCA) than did nonaffected controls. The ALS males also had significantly lower PCA than PD males, although no significant differences were
observed between female ALS and PD patients. The PD patients of either sex
had a lower PCA when compared to controls, but the differences were not
statistically significant. The observed differences in PCA were due solely to
increased medullary width, suggesting that the diminished cortical bone
thickness resulted from greater bone resorption rather than differential bone
growth. Longitudinal studies support the cross-sectional findings of accelerated bone loss among ALS patients. It is not possible to determine from the
present data whether the observed differences in PCA of the second metacarpal of the ALS patients are due to atrophy of the first interosseous muscle, to a
generalized resorption process inherently associated with the development
and progression of ALS,or to factors not accounted for by the present analysis.
We previously demonstrated a lower bone
mass in neurologically normal children, adolescents, and adults from the island of
Guam, compared to other ethnic groups in
the continental United States (Plato et al.,
1982,1984). In the present report, we evaluated the bone mass in Guamanian patients
with amyotrophic lateral sclerosis (ALS)and
parkinsonism-dementia (PD), two neurodegenerative disorders occurring in high incidence among Guamanians. Clinically, ALS
on Guam is the same as that described by
Charcot more than one hundred years ago. It
is a disease of the motor neurons and the
@ 1989 ALAN R. LISS. INC.
corticospinal tract, characterized by muscle
weakness, progressive muscle atrophy, paralysis and spasticity. Neuropathologically,
Guamanian ALS is similar to classical ALS
worldwide, except that it is often associated
with neurofibrillary tangles in the brain and
spinal cord. The second neurological disorder, PD, is found in equally high incidence on
Guam and is often encountered together
Received October 12,1987; accepted November 4,1988.
Address reprint requests to Dr. Ralph M. Garmto, Building 36,
Room 5B-21, National Institutes of Health, Bethesda, Maryland
20892.
108
R.M. GARRUTO ET AL.
with ALS in the same family, the same sibship, and occasionally in the same individual. Parkinsonism-dementia is characterized clinically by bradykinesia (slowness of
voluntary motor activity), muscular rigidity,
and tremor. It is always accompanied by an
early onset progressive dementia. Neuropathologically PD is associated with severe
neuronal loss and neurofibrillary tangles
but, unlike Alzheimer disease, senile
plaques are not usually seen. The objective of
the current study was to determine if a lower
bone mass was primarily associated with the
disease process or was a secondary consequence ofimmobility or other factors, such as
age, sex, and menopause. During the past
decade, systematic and intensive investigations on the etiology and pathogenesis of,
and pathogenetic relationship between, ALS
and PD of Guam have revealed subtle defects
in mineral metabolism and selective intra-
neuronal deposition of calcium, aluminum,
and silicon in brain and spinal cord of these
patients (Garruto, 1988; Garruto et al., 1984;
Garruto and Yase, 1986; Yanagihara et al.,
1984).
MATERIALS AND METHODS
Bilateral hand-wrist radiographs were obtained from 31 Guamanian patients (15
males, 16 females) with ALS,67 patients (39
males, 28 females) with PD, and 66 neurologically normal Guamanian controls (34
males, 32 females). Diagnoses were clinically verified by neurologists at the National
Institute of Neurological Disorders and
Stroke (NINDS) Research Center on Guam,
and registered patients were examined at
three- to six-month intervals. Informed consent was obtained from all participants. Patients were rated for degree of disability (see
criteria in Table 1) with 0 indicating no
TABLE 1. Disability categories for patients with amyotrophic lateral sclerosis a n d parkinsonism-dementia
of Guam and percent of patients in each category
Disability
score
0
Disability
category
None
1
Mild
2
Moderate
3
Marked
Amyotrophic lateral sclerosis
Criteria
Percent
No weakness or muscle atrophy
Mild weakness and muscle
atrophy
Unable to work, yet able to
care for self; fully ambulatory
Moderate weakness and muscle
atrophy
Requiring help in dressing,
bathing, eating, daily
functions; needs assistance
with walking
Marked weakness and muscle
atrophy
Requiring total or nearly total
nursing care; confined to bed
or wheelchair
0
41
25
34
Parkinsonism-dementia
Criteria
Percent
No bradykinesia', tremor,
rigidity, dementia
Mild bradykinesia, tremor,
rigidity, dementia
Unable to work, yet able to
care for self; fully ambulatory
Moderate bradykinesia, tremor,
rigidity, dementia
Requiring help in dressing,
bathing, eating, daily
functions; needs assistance
with walking
Marked bradykinesia, tremor,
rigidity, dementia
Requiring total or nearly total
nursing care; confined to bed
or wheelchair
2
43
28
27
'Bradykinesia refers to the slowness of voluntary motor activity.
TABLE 2. Mean age, age range, a n d mean disability scores of Guamanian patients with amyotrophic lateral
sclerosis a n d parkinsonism-dementia a n d nonaffected controls
Disease
category
Amyotrophic lateral sclerosis
Male
Female
Parkinsonism-dementia
Male
Female
Control
Male
Female
No. of
individuals
mean i SE
(years)
range
(years)
15
16
53.13 k 2.72
52.19 2.49
+
35-71
33-66
39
28
60.74 f 1.39
60.07 f 1.54
43-81
48-76
34
32
53.76 5 1.57
52.25 1.83
38-82
33-71
*
109
BONE LOSS IN ALS AND PD OF GUAM
disability, 1 indicating mild, 2 indicating
moderate, and 3 indicating marked disability. All controls had disability scores of zero.
Percentages of patients characterized by the
various degrees of disability are also listed in
Table 1;thus, it becomes evident that while
the end result of disability in each score is
comparable between ALS and PD, the components and the diagnostic criteria for each
score are not the same in both diseases.
Table 2 summarizes the mean age and age
range for ALS and PD patients and controls.
To evaluate differences in the rate of bone
loss over time, we collected serial radiographs from 17 ALS patients (7 males, 10
females), 27 PD patients (17 males, 10
females), and 22 nonaffected controls (9
males, 13 females) between 1977 and 1981.
Most participants had only two serial X-rays,
although some had as many as five.
Total subperiosteal diameter (T) and medullary width (M) of the second metacarpal
bone were measured directly from the radiographs (Fig. l),utilizing a dial-reading caliper with 0.05 mm readout capability (Garn,
1970; Plato and Norris, 1980). Percent cortical area (PCA), derived from T and M, where
PCA = [(T2 - M2)/T21 x 100, was selected,
instead of cortical thickness, as the indicator
of bone mass, because it accounts for differences in bone size. The data were analyzed
utilizing standard methods by t-tests, analysis of variance, and linear regression analysis. Analysis of variance comparisons were
tested using Duncan's multiple range test
(Duncan, 1975) and Bonferroni's t-test
(Miller, 1981).
RESULTS
The PD patients were approximately
seven years older than ALS patients and
controls (Table 2). Mean age differences be-
100 I
I
I
I
1
I
90 -
80 -
70 0
I-
8
0
601
1
30
20
30
40
50
60
70
80
90
AGE
Fig. 1. Scatter diagram and regression lines of percent cortical area of the left second metacarpal bone on
age in male Guamanian patients with amyotrophic lateral sclerosis (ALS), parkinsonism-dementia (PD), and
in nonaffected controls.
tween PD patients and ALS patients by sex
were significant (P < .Ol), as were differences between PD patients and controls (P <
.01). Significant differences were not found
in ages of male or female ALS patients and
their respective controls. The percent of ALS
and PD patients in each disability category is
shown in Table 1.There was no significant
difference between A L S and PD in the number of patients in each disability category.
There was also no significant difference in
the mean PCA value between patients with
different disability scores, except in male
ALS patients between those with disability
scores of 1and 3. It seems, therefore, that the
degree of overall disability has little effect on
the PCA of the second metacarpal of male
ALS patients and no effect at all on the PCA
TABLE 3. Bilateral measurements o f the second metacarpal bone of Guamanian patients with amyotrophic
lateral sclerosis (ALS) and parkinsonism-dementia (PO)and nonaffected controls
Sex
Male
Female
Disease
category
N
ALS
PD
Control
ALS
PD
Control
15
39
34
16
28
32
Left hands
Subperiosteal
Medullary
diameter
width
Mean f SE
Mean k SE
8.71 f 0.18
8.94 !r 0.1 1
8.76 i 0.11
7.98 f 0.16
7.81 0.11
7.74 0.09
*
+
4.01
3.65
3.14
3.63
3.66
3.02
f 0.39
-I 0.14
i 0.17
f 0.27
f 0.16
0.17
+
Right hands
Subperiosteal
Medullary
diameter
width
Mean SE
Mean f SE
+
9.23 + 0.21
9.23 k 0.14
9.12 !r 0.11
8.21 f 0.17
8.10 k 0.12
8.07 0.10
+
4.29 f 0.44
3.96 f 0.16
3.40 0.18
3.70 f 0.32
4.01 k 0.18
3.16 f 0.19
+
110
R.M. GARRUT0 ET AL.
of female ALS patients, or of PD patients of
either sex.
No significant differencesin total subperiosteal diameter and medullary width were
found between disease categories (Table 3).
Likewise, with the exception of male and
female controls, no significant bilateral differences were found. However, male and female controls had a significantlylower medullary width (I' < .01)than either ALS or PD
patients.
Comparisons of bone mass between ALS
patients, PD patients, and controls were performed using the PCA of the left (or nondominant) hand. Since analysis of variance of
PCA in terms of age, sex, diagnosis, and
disabilitystatus gave significant F values for
TABLE 4. Analysis of variance: Percent cortical area
of the second metacarpal bone of Guamanian patients
with amyotrophic lateral sclerosis and
parkinsonism-dementia and nonaffected controls
Source
d.f.
Total
Error
Model
Age
Sex
Diagnosis
Disability
109
102
7
Sum
squares
Mean
squares
F
value
P
10,663
7,585
3,078
1,207
325
758
788
74
440
1,207
325
379
263
5.94
16.31
4.39
5.12
3.55
,0001
,0001
.039
.008
.017
1
1
2
3
I00
I
b
A
Male
I
-
Disease
category
N
PCA
Mean =k SE
ALS
PD
Control
ALS
PD
Control
15
39
34
16
28
32
76.05 k 2.21
84.09 3z 1.41
85.24 f 1.48
16.72 f 2.05
79.25 f 1.61
82.70 k 1.46
~~~
Female
~~~
TABLE 6. Multivariate analysis of variance: Percent
cortical area (PCA) of the second metacarpal bone
of Guamanian patients with amyotrophic lateral
sclerosis (ALS) and parkinsonism-dementia (PD) and
nonaffected controls adjusted for age
Sex
Contrast
Sum of
squares
F value
P
Male
ALS vs. PD
ALS vs. Control
PD vs. Control
ALS vs. PD
ALS vs. Control
PD vs. Control
647
883
21
59
380
156
9.05
12.34
0.30
0.90
5.78
2.36
.0035
,0007
.5856
.3453
,0188
,1287
Female
-
_-A.
-
Ao OiSo
-
$3
80 -
A
70 -
0.
*O
0.
60 -
40 -
Sex
all four variables (Table 4), further comparisons were made by diagnosis, sex, and age
~ O U D Fimre
.
1 shows the scatter diamam
tion for the female comparisons. Table 5
presents the age-adjusted mean percent cortical area by sex and diagnosis. In both sexes,
nonaffected controls have the highest mean
PCA and the ALS patients have the lowest.
The mean PCA of PD patients lies between
those of the controls and ALS patients, but
closer to the former. Statistical comparisons
of these means, through multivariate analysis of variance, shown in Table 6, indicate
that 1)the differences in PCA between ALS
patients and controls are statistically significant in both males and females, 2) differences between PD patients and controls are
not statistically significant in either sex, and
KO
-
=A."*.A"$
90 -
50-
$
TABLE 5. Age-adjusted mean percent cortical area
(PCA) of the second metacarpal bone of Guamanian
patients with amyotrophic lateral sclerosis (ALS) and
parkinsonism-dementia (PD) and nonaffected controls
i-np0-i
-*
ALS
---A
CONTROLS
08
-
-
Fig. 2. Scatter diagram and regression lines of percent cortical area of the left second metacarpal bone on
age in female Guamanian patients with amyotrophic
lateral sclerosis (ALS), parkinsonism-dementia (PD),
and in nonaffected controls.
the PEA of ALSYpatients is lower than those
ofPD and controls at all ages of both sexes.
Because of differences in the mean age of
onset between ALS and PD patients, the
111
BONE LOSS IN ALS AND PD OF GUAM
participants were separated into three age
groups: younger than 50 years (<50), between 50 and 59 years (50-59), and 60 years
or older (360). Table 7 shows the mean ages
and mean PCA by sex, disease category, and
age group. This age grouping was more critical in females, as 9 of 32 controls, 5 of 16ALS
patients, and none of the 28 PD patients
were below the average age of menopause
(46.6 years) of Guamanian women (Plat0 et
al., 1982). No statistically significant differences in the mean age were found between
disease categories within age groups.
Among females in the <50 age group, no
significant differences in PCA were found
between any of the disease categories. Both
female PD patients in this age group were
postmenopausal, while the ages of 5 of the 7
ALS patients and 7 of the 11 controls were
below the average menopausal age. Among
younger males, ALS patients had the lowest
PCA. However, the only significant difference was betweenALS and PD patients (P <
.01). In the 50-59 age group, male and female ALS patients had the lowest PCA, and
controls of either sex had the highest. In
males, the differences in PCA between ALS
patients and controls and between ALS and
PD patients were statistically significant (P
< .01). In females, significant differences ( P
< .01) were found only between ALS patients
and controls. In the 260 age group, the mean
PCA of the ALS patients was again the lowest, and those of the nonaffected controls the
highest. However, the differences between
disease categories were not significant.
The mean age of onset for ALS was 46.9
years in males and 46.3 in females, while the
mean age of onset for PD was 55.8 in males
and 55.3 in females. A significantly negative
correlation ( r = -0.52, P < .001) was found
between the age of onset of PD in males and
PCA. By contrast, no significant correlation
was found between the age of onset and PCA
in male and female patients with ALS, and in
female PD patients.
The duration of disease (from onset to
radiographic examination) for ALS was 6.26
years in male patients and 5.9 years in female patients. The duration for PD was 4.7
and 4.2 in male and female patients, respectively. No significant correlations were
found between duration of disease of either
ALS or PD and PCA, except in males the
youngest age group ( 4 0years) had a significantly negative correlation of -0.79 ( P <
.05).
Comparisons between disability and disease duration for male or female ALS patients were nonsignificant when age groups
were studied separately. There were, however, significant correlations ( r = 0.56, P <
.03 in ALS males; r = 0.69, P < .003 in ALS
females, and r = 0.53, P < .006 in PD females) when age groups were pooled. Correlations between disability and duration of
PD in males were not significant.
The longitudinal analysis of PCA by disease category is summarized in Table 8. The
average annual regression coefficient is the
average of the individual regression coefficients of participants from their first to last
visit. With the exception of the control females (who were also the youngest), all
groups had a negative correlation with age.
Only the coefficients for ALS male and PD
female were significantly (P < .05) different
from zero. Comparisons between pairs of
coefficients resulted in statistically significant differences between ALS and PD males
(P < .Ol), ALS and control males (P < .05),
and PD and control females (P < .05).
TABLE 7 . Mean percent cortical area (PCA) of the second metacarpal bone of Guamanian patients with
amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) and nonaffected controls
Age
group
(years)
<50
50-59
260
Disease
category
ALS
PD
Control
ALS
PD
Control
ALS
PD
Control
N
Male
Age f SE
(years)
PCA f SE
N
7
2
9
3
16
16
5
21
9
44.1 f 2.0
44.5 f 1.5
43.0 f 1.2
53.7 f 0.7
54.4 f 0.7
53.6 f 0.7
65.4 f 2.0
67.1 1.3
64.9 f 2.3
82.9 f 0.4
89.0 f 3.5
87.8 f 2.0
66.2 f 9.3
85.0 f 1.6
87.3 f 1.8
75.6 f 7.9
80.6 f 1.3
82.5 f 3.3
6
2
*
11
6
11
14
4
15
7
Female
Age f SE
(years)
*
41.7 2.4
48.5 5 0.5
40.8 f 1.6
53.3 k 1.6
53.5 f 0.8
54.4 0.8
63.2 3~ 1.6
66.5 f 1.3
66.0 f 1.5
+
PCA & SE
85.7 f 4.3
81.0 f 4.7
87.3 f 2.6
73.2 4.2
79.7 f 3.0
85.8 f 1.4
73.5 3.5
74.8 2.0
74.9 f 2.7
+
**
112
R.M. GARRUTO ET AL.
T A B L E 8. Longitudinal analysis of the progressive loss o f percent cortical area in Guamanian patients with
amyotrophic lateral sclerosis ( A L S ) and parkinsonism-dementia (PD)and nonaffected controls
Sex
Male
Female
Disease
category
No. of
individuals
Average annual'
regression + SE
Mean age
(years)
1st visit
Age range
(years)
1st VlSlt
Mean2
interval
(years)
ALS
PD
Control
ALS
7
17
9
10
10
13
-5.15 f 2.02
-0.62
0.39
-0.49 -+ 0.42
-2.49
1.72
-2.79
1.17
0.22 zk 0.52
50.1
61.3
54.2
53.1
59.2
44.2
35-68
53-82
26-82
39-67
50-75
24-60
1.7
2.9
2.6
2.5
2.4
2.3
PD
Control
+
*+
'Average of the individual annual regression ciiefficients of percent cortical area on age.
"Mean number of years between first and last visit.
DISCUSSION
Our data indicate that nonaffected neurologically normal Guamanian males have a
higher PCA than either ALS or PD patients
of the same age and sex, and ALS patients
have the lowest, although these differences
are not always statistically significant. ALS
patients of either sex have a significantly
lower PCA than do controls of the same age
and sex. Male ALS patients also had significantly lower PCA in the second metacarpal
than did male PD patients. Differences between PD and nonaffected controls were
nonsignificant in both males and females. In
evaluating these results, one is confronted
with the inherent differences in bone mass
related to sex, age, menopausal status, age of
onset of the disease, and degree and duration
of immobility and disability.
The contributions of sex and age were
controlled (with one exception) by analyzing
the male and female data separately by age
groups. The only exception was in the 4 0 year-old group, where both female PD patients in this age group were postmenopausal. Their mean age was also significantly higher than that of female ALS
patients, or controls in the same age group.
This inter-group age difference could account for the lower PCA in the PD women.
While the older age and the postmenopausal
status of the <50-year PD females may be
responsible for their lower PCA, these factors cannot account for the lower PCA values
of the ALS male, or the female ALS patients
in the remaining age groups.
Age of onset of either ALS or PD did not
show consistent correlations with PCA. It is
not clear from our data why the later onset of
PD in males resulted in less cortical bone.
Immobilization is known to enhance bone
loss. However, disability could not account
for the differences in PCA between ALS and
PD patients, since their disability scores
were not significantly different. One could
argue, however, that differences in age of
onset and/or the duration of disability prior
to radiographic examination may be important factors in determining the amount of
bone loss. Even though our data showed
associations between duration of disease and
disability, we found no consistent correlation
between the duration of either ALS or PD
with PCA. It is possible that patients with a
longer duration have a less severe form of the
disease so that, even though the duration
from onset to death is longer, the overall
extent of immobilization may be no greater
than in patients with a shorter duration.
Indeed, the only significant correlation between duration and PCA was found in the
youngest (<50 years) ALS males.
Our results indicate that, while ALS and
PD patients have similar disability scores,
the former consistently have lower PCA values. Two questions emerge: first, is the measure of disability in the two diseases comparable, and second, how does the measure of
disability relate to the bone being measured?
Although the end result for the degree of
disability in Table 1 is the same for ALS and
PD, the criteria used in deriving the degree
of disability for each disease are not. In ALS,
the criteria revolve around the issue of weakness and muscle atrophy, whereas in PD the
major criteria are slowness of voluntary
movement and rigidity. An earlier study
(Plato and Norris, 19801,indicated that bone
remodelling responds to the amount of physical stress exerted on the bone by the muscle.
Thus, progressive muscle atrophy in ALS
may have a more profound effect on bone
mass than on overall immobility. Furthermore, ALS involves the atrophy of one of the
BONE LOSS IN ALS AND PD OF GUAM
muscles attached to the bone (second metacarpal) being measured. Hence, the similarity in the overall immobility between A L S
and PD notwithstanding, the second metacarpal bone of ALS patients should be losing
more bone than that of PD patients. In other
words, the effect of disability and immobility
on bone remodelling may be preferential and
not always generalized.
An analysis of the longitudinal data suggests that male ALS patients lose bone more
rapidly than either male PD patients or nonaffected controls, and that female PD patients similarly have a higher rate of bone
loss than do female controls. Our longitudinal data do not permit a full ascertainment of
the sources of variation in bone loss. Because
of the small number of participants in each
category, it was impossible to adjust adequately for age or duration of disability. The
size of the data set notwithstanding, the
results of the longitudinal analysis offer additional support to the conclusions of the
cross-sectional analysis.
Our present results from hand-wrist radiographs of Guamanian patients with ALS
and PD support the notion that once the
intervening factors of age, sex, menopause
status, disease duration, and immobility and
disability are controlled, there is still a significant difference in bone PCA between
ALS patients and Guamanian controls of
either sex and between male ALS and male
PD patients. This point is supported by a
recent report by Glasberg et al. (1987a) who
studied bone mineral content through single
photon absorptiometry in the radius of
United States ALS patients. They also found
increased incidence of osteopenia in the patient group, which could not be accounted for
by disability. Whether the PCA differences
are the result of weakness and atrophy of the
second interosseous muscle in ALS or are
due to a generalized bone demineralization
associated with calcium deficiency, toxic
metals, and metabolic dysfunction in these
disorders on Guam (Garruto et al., 1985;
Garruto and Yase, 1986; Glasberg et al.,
1987a; Glasberg et al., 1987b1,or a combina-
113
tion of both factors, could not be ascertained
from the present data.
LITERATURE CITED
Duncan DB (1975) t-Tests and intervals for comparisons
suggested by the data. Biometrics 32:339-359.
Garn SM (1970) The Earlier Gain and Later Loss of
Cortical Bone. Springfield, I L Charles C. Thomas.
Garruto RM (1989) Amyotrophic lateral sclerosis and
parkinsonism dementia of Guam: Clinical, epidemiological and genetic patterns. Am. J . Hum. Biol. (in
press).
Garruto RM, Fukatsu R, Yanagihara R, Gajdusek DC,
Hook G, and Fiori CE (1984) Imaging of calcium and
aluminum in neurofibrillarv tangle-bearing neurons
in parkinsonism-dementia df GuLm. Proc. Gatl. Acad.
Sci. U S A . 82:1875-1879.
Garmto RM. Yanaeihara R. and Gaidusek DC (1985)
Disappearance oT high incident aGyotrophic lateral
sclerosis and Parkinson-dementia of Guam. Neurology
35:193-198.
Garruto RM, and Yase Y (1986) Neurodegenerative disorders of the Western Pacific: The search for mechanisms of pathogenesis. Trends Neurosci. 9:36%374.
Glasberg M, Gross B, Kleerekoper M (1987a) Bone mineral content and osteopenia in amyotrophic lateral
sclerosis. Book of Abstracts, International Conference
of Amyotrophic Lateral Sclerosis, October 29-31,
1987, Kyoto, Japan, p. 117.
Glasberg M, Kleerekoper M, and Glasberg J (1987b)
Parathyroid metabolism and calcium homeostasis in
ALS. Book of Abstracts, International Conference of
Amyotrophic Lateral Sclerosis, October 29-31, 1987,
Kyoto, Japan, p. 77.
Miller RG, Jr (1981) Simultaneous Statistical Inference.
New York: Springer-Verlag.
Plato CC, Garruto RM, Yanagihara RT, Chen KM, Wood
JL, Gajdusek DC, and Norris AH (1982) Cortical bone
loss and measurements of the second metacarpal bone:
I. Comparisons between adult Guamanian Chamorros
and American Caucasians. Am. J. Phys. Anthropol.
59:461465.
Plato CC, Greulich WW, Garruto RM,and Yanagihara R
(1984) Cortical bone loss and measurements of the
second metacarpal bone: 11. Hypodense bone in postwar Guamanian children. Am. J. Phys. Anthropol.
6357-63.
Plato CC, and Norris AH (1980) Bone measurements of
the second metacarpal and grip strength. Hum. Biol.
52:131-149.
Yanaghara R, Garruto RM, Gajdusek DC, Tomita A,
Uchikawa T, Konagaya Y, Chen KM, Sobue I, Plato
CC, and Gibbs CJ (1984) Calcium and vitamin D
metabolism in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia.
Ann. Neurol. 25:42-48.
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