名古屋学芸大学健康 ･ 栄養研究所年報

創刊号

２００７年

《Original Article》

Factors related ultrasonic bone density in subacute myelo-optico
neuropathy (SMON) patients
Katsumi Yamanaka＊ and Nakako Fujiwara＊＊

Abstract
Objective: To clarify the bone mineral density (BMD) in female sub-acute-myelo optico neuropathy(SMON) patients, and the relationship between BMD and their life style. Design: The study populationconsisted of 65 female SMON patients aged 28-89 years old living in Aichi Prefecture. BMD was measured
as stiffness (St) by using an ultra sonic bone densimeter (A-1000 Achilles of Lunar Corp). Height, weight,BMI, history of childbirth and delivery, onset age of menopause, intake of milk, intake of small fish, Barthel
Index, the number of retaining teeth, and a history of bone fracture were used as factors of life style. Results:
Average percent age-adjusted St (Adjusted St) and standard deviation (SD) was 88.4±13.2. The rate of patientswith low Adjusted St (less than 89) was higher in patients with low height, light weight and low BMI, withhistory of childbirth and delivery, with early onset of menopause, and with low intake of milk. There werenot seen to be large differences between two groups in SMON severity (severe and moderate, and slight andnone), in Barthel Index (less than 99 and 100), in the number of retaining teeth (less than 19 and 20 or more).
Conclusion: Factors related St were height, weight, history of childbirth and delivery, onset of menopause
and intake of milk. Average St in female SMON patients was lower than the average St of Japanese healthy
females within the same age group.

Introduction
There were reports from many patients who were prescribed a drug (5-chloro-7-iodo-8-hydroxyl-quinolin,which are also called clioquinol or chinoform) in Japan in the years around 1950-1960. This drug was usedwidely as an anti-amaebicidal and anti-bacterial drug in Japan. The total number of patients reached over
9,000 according to a national survey in 1970. This drug-adverse disease was called sub-acute myelo-optico
neuropathy (SMON) [1]. SMON typically started with sub-acute or sometimes acutely abdominal pain, diarrhea
followed by dysesthesia (impairment of the senses) in the lower half body, paralysis and visual disturbances.
The Ministry of Health and Welfare recognized SMON as a drug-adverse disease in 1960. Since 1960, theMinistry has formed SMON research committees, and has supported SMON patients by examining their healthcondition. In Aichi Prefecture, there were around 400 patients in 1960. Since 1960, the Aichi-prefecture SMON
research committee has examined SMON patients in cooperation with The Aichi Prefecture SMON patientgroup. An examination of ultrasonic bone density was conducted in 1994-1997. We would like to report some

＊ Nagoya University of Arts and Sciences＊＊ School of Nursing, Nagoya City University

19results of this examination.

Method
1, ParticipantsParticipants were female SMON patients who lived in Aichi prefecture, and took the general SMON
examination including ultrasonic bone density measurements from 1994 to 1997.
2, Body indices
Height and weight were measured, and the body mass index (BMI) was calculated.
3, History of menstruation and delivery
The onset age of menopause and history of childbirth and delivery were noted.
4, Nutrition
Frequency of intake of milk and intake of small fish were noted.
5, SMON severity
SMON patients had sensory disturbances, motor dysfunction and visual disturbances. These disturbancesand dysfunction were integrated into a comprehensive severity scale according to 5 levels: extremely severe,severe, moderate, slight and none. This level of severity was called SMON severity, and this definition ofseverity adopted by the Japan SMON research committee has been used since 1960.
These levels of severity were diagnosed by neurologists of SMON research committee in the SMON
examination.
6, Barthel Index
Measurements for assessing daily life activities and disability used the Barthel Index (BI). BI shows a sum
score value range from 0 (dependence) to 100 (independence) according to 10 personal activities [2].
7, History of bone fracture
History of bone fracture in the past was noted.
8, Ultrasonic bone density measurements
We evaluated the index stiffness (St) which was calculated from the speed of sound (SOS) and broadband
ultrasonic attenuation (BUA) on the os calcis using an ultra sonic bone densitometer (A-1000 Achilles ofLunar Corp) [3]. From the St, percentage- adjusted St (Adjusted St) was calculated [4]. Adjusted St shows thepercentage of the average St of the Japanese healthy female of the same age group. As the average Adjusted
St of healthy female in age, we used output data from A-100 Achilles.
9, Data analysis
Bivariate analysis was carried out by chi-square test to determine the statistical difference between thetwo groups. The level of significance was set at p<0.05.

20Factors related ultrasonic bone density in subacute myelo-optico neuropathy (SMON) patientsResults
1, Participants
The number of patients who participated in this research was 65 females. The average and standard
deviation of age was 67.5 ± 9.9 and it’s range was between 28 to 89.
2, SMON severity
The number of patients in each rank of severity were one (1.5%) in extremely severe, 4 (6.2%) in severe,36 (55.4%) in moderate, 22 (33.8%) in slight and 2 (3.1%) in none.
.
3, ultrasonic bone density
SOS, BUA, St and Adjusted St on the os calcis were shown in Table 1. Average Adjusted St and SD was
88.4±13.2. The number of patients according to Adjusted St is shown in Table 2. Then number of patients inAdjusted St 80-89 was the largest. Average Adjusted St in SMON patients was 11.6% lower than the average
St of Japanese females in the same age group.
4, The relationship between Adjusted St and the factors
We analyzed the relationship between Adjusted St and the factors which were considered to be related tobone density. We defined Adjusted St 90 or more as normal BMD. Height, weight, BMI, history of childbirthand delivery, the age of menopause, intake of milk, intake of small fish, SMON severity, Barthel Index, andthe number of retaining teeth were used as the factors to determine this. The relationship between the factors
and the rate of patients with normal Adjusted St is shown in Table 3.
The rate of patients with normal Adjusted St was significantly higher in patients with weight being 50 kg
or more, height 150 cm or more, BMI 22 or more than in patients with weight less than 49 kg, height less than
149 cm and BMI less than 21. The rate of patients with normal Adjusted St was significantly higher in patients
without a history of childbirth and delivery, 50 years or more of according to the onset age of menopause thanin patients with history of delivery and less than 49 years of the onset of age of menopause. Concerning food,Table 1. Speed of sound (SUS), Broadband ultrasonic attenuation (BUA),
stiffness (St) and percent age-adjusted St (Adjusted St) in SMON patients
N=65
Mean

S.D.

SUS (m/sec)

1494.3 ±22.0

BUA (dB/MHz)

93.6 ±11.3

St61.0 ±11.3

Adjusted St

88.4 ±13.2

Table 2. Number of patients according to Adjusted St
N=65
Adjusted St

number of patients (%)

Less than 79

1589-892399-9919

100 or more821

Table 3. Number of patients with normal Adjusted St (90 or more) according to factors
Factors

total numberwith normal Adjusted St
Numberweight (kg)%significanceless than 49

391333.350 or more

26

1557.7less than 149

371437.8150 or more

28

1340.4less than 21

41

15

36.6

22 or more

231252.2history of childbirth and delivery

yes27

1436.8deliveryno38

1348.1less than 49

29827.6

50 or more2816

57.1

less than 19

12866.7

20 or more

18

11

61.1

take often

21628.5

not take often

442045.5＊take often

211047.6＊

not take often

44

16

35.4

severe or moderate

40

17

42.5

slight or none

24

10

41.7

less than 99

23

10

43.5

100

42

17

40.5

yes

22

7

31.8

no43

27

62.8

height (cm)BMI

onset age of menopause

number of retaining teeth

milk

small fish

severity

Barthel Indexhistory of bone fracture

＊
＊

＊

＊

n.s.

n.s.

n.s.

＊

＊ p<0.05 (x test)
n.s. : not significant2the rate of patients with normal Adjusted St was significantly higher in patients who consumed milk more often
than those who didn’t. However, the rate of patients with normal Adjusted St was lower in patients who ate
small fish more often than those who did not eat small fish so often. The rate of patients with normal Adjusted
St was significantly lower in patients with history of bone fractures than without a history of bone fractures.
There were not seen to be large differences between two groups in the SMON severity groups (severe andmoderate, and slight and none), in Barthel Index (less than 99 and 100), in the number of retaining teeth (lessthan 19 and 20 or more).
There were 22 (33.8%) patients with a history of bone fractures out of 65. There were a dose-response
relationship between the rate of patients with a history of bone fractures and Adjusted St as shown in Figure
1.

22Factors related ultrasonic bone density in subacute myelo-optico neuropathy (SMON) patients

Figure 1 Percent of patients with history of bone fracture according to Adjusted St

Discussion
A history of bone fractures was seen in 129 (12.4%) out of 1042

SMON patients according to thenational SMON examination in 1996 [5]. The cause of fractures in SMON patients is thought to be that theytend to fall easily due to disturbances when standing or walking due to spasms of the legs and the decrease inmuscle strength. Another cause is thought to be that the fragility of bone increased, because of motor disturbances. For predicting fracture risk or prophylactic strategy against osteoporosis, bone density assessment isindispensable. There is a lot of evidence to support the use of ultrasound bone density for the assessment offracture risk in elderly women [6]. The Ultra sound bone densitometer is helpful equipment for assessing therisk of fractures over a large population, because of its low cost, good portability, relatively short examination
time, and a protection space against radiation is deemed not necessary. Calcaneal ultrasound bone density
correlated well with calcaneal bone mineral density assessed by single X-ray absorptiometry and dual energy
X-ray absorptiometry which has been widely used in hospitals [3,4].
In this study, the average Adjusted St in female SMON patients was lower than 100. The number ofpatients which showed more than 100 in Adjusted St was 8 out of 65. The research in Okayama Prefectureusing the same ultrasonic densimetry reported that stiffness in SMON patients tended to be lower that of nonSMON people [7]. Ando reported that he diagnosed osteoporosis in 38 SMON patients out of 64 using DPX,
and lumbar roentgenogram with osteoporotic changes [6]. Knowledge of low bone St by SMON patients isimportant as this will motivate them in preventing bone fractures by avoiding falls, improving their nutrition
and increasing their exercise.
In this study, the rate of patients with low Adjusted St was higher in SMON patients with history of childbirth and delivery than those with no history. The rate of patients with low Adjusted St was higher in SMON
patients with the onset age of menopause less than 49 years than 50 years or over. This was not contradiction
against the previous papers which showed a late menopause was a decreased risk for low BMD [9,10].
Milk or small fish are rich in calcium The rate of patients with normal Adjusted St was higher in patients
who drink milk more frequently [11-14]. However, the rate of normal Adjusted St was lower in patients who eat
small fish more often. The cause of this contrary result is not clear. Confronting factors may exist. Concerning

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ADL, there was not a large difference in Adjusted St between patients with severe or moderate and slight ornone. There was also not a large difference in Adjusted St between patients with Barthel Index 100 and lessthan 99. This result is different from previous papers [12-14] which showed that mobile handicapped people
had low bone density. Whether this result relates with the character of SMON or not is unclear.
In this study, there is a relationship between history of bone fractures and Adjusted St. One of the causesof bone fractures is considered to be due to decreased bone density.

References
1)

The national institute of health: Review on SMON. Japanese Journal of Medical Science & Biology. 1975: 28, 1-2932)

Mahoney FT, Barthel DW. Functional evaluation; The Barthel index. Maryland State Medical Journal 1965; 14: 61-65

3)

Yamazaki K, Kushida K, Ohmura M, Sana M, Sato Y, Inoue T. Ultrasound bone densitometry of the os calcis. TherapeuticResearch (1992) 13: 585-593.

4)

Yamazaki K, Kushida K, Ohmura M, Sana M, Inoue T. Ultrasound bone densitometry of the os calcis in Japanese women.
Osteoporosis international (1994) 4: 220-225.

5)

Iida M, Ando H, Yamada T, Kachi T, Tamura T, Harada A. Osteoporosis in subacute myelo-optico neuropathy. Heisei 8
Annual report of SMON research committee (1997) 17-22.

6)

Yuh I, Yamamoto I, Ohnaka Y, Takada M, Nakajima K, Masuda K, Murata K, Morita R, Clinical evaluation of ultrasonicmeasurement of the calcaneal bone. Nihon Houi Kaisi (1993) 53: 1340-1346.

7)

Yamada M, Takayanagi T, Omae R. Bone mineral density of the patients with subacute myelo- optico-neuropathy (SMON).
Heisei 5 Annual report of SMON research committee (1994) 158-161.

8)

Ando H, Yamada T, Kachi T, Tamura T, Harada A. Osteoporosis in subacute myelo-optico neuropathy. Heisei 1 Annualreport of SMON research committee (1990) 235-238.

9)

Osei-Hyiaman D, Satoshi T, Ueji M et al. Timing of menopause, reproductive years, and bone mineral density: a crosssectional study of postmenopausal Japanese women. Am J Epidemiology 1998; 148: 1055-61

10) Shilbayeh S. Prevalence of osteoporosis and its reproductive risk factors among Jordanian women: a cross-sectional study.
Osteoporos Int 2003 14: 929 40
11) Cussier EC, Going SB, Houtkooper LB et al. E Exercise frequency and calcium intake predict 4-year bone changes inpostmenopausal women. Osteoporos Int 2005; 16: 2129-4112) Uusi-Rasi K, Sievanen H, Vuori I et al. Association of physical activity and calcium intake with bone mass and size inhealthy women at different ages. J Bone Miner Res 1998; 13: 133-4213) Uusi-Rasi K, Sievanen H, Pasanen M et al. Maintenance of body weight, physical activity and calcium intake helps
preserve bone mass in elderly women. Osteoporos In 2001; 12: 373-914) Uusi-Rasi K, Sievanen H, Pasanen M et al. Association of calcium intake and physical activity with bone mass and sizein premenopausal and postmenopausal women: a peripheral quantitative computed tomography study. J Bone Miner Res
2002; 17: 544-52

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Factors related ultrasonic bone density in subacute myelo-optico neuropathy (SMON) patients

和文抄録

スモン患者の骨密度とその関連する要因について
山中克己

＊

＊＊

藤原奈佳子

女性スモン患者の骨密度の状況とその骨密度と関連する要因について検討した。愛知県に在住する28－89歳の65人の女性スモン患者を対象に検診をおこなった。骨密度の測定は Lunar Corp 社のアキレス A1000を使用し、stiffness を用いた。要因は身長、体重、BMI、出産歴、閉経年齢、ミルク、小魚の摂取状況、スモン障害度、Barthel Index、歯数、骨折の既往歴をとった。年齢補正 Stのパーセント値の平均は88.4±13.2であった。要因を ２ 群に分けて分析すると、低骨密度（年齢補正 stiffness が89以下）は低身長、低体重、低 BMI、出産歴あり、低閉経年齢、ミルクの摂取の多い患者に多かった。女性スモン患者の stiffness は同年齢の健康女性の stiffness より低かった。

＊名古屋学芸大学＊＊名古屋市立大学

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