Osteoporos Int (2011) 22:133141

DOI 10.1007/s00198-010-1238-x

ORIGINAL ARTICLE

Impact of smoking on bone mineral density and bone

metabolism in elderly men: the Fujiwara-kyo Osteoporosis
Risk in Men (FORMEN) study
J. Tamaki & M. Iki & Y. Fujita & K. Kouda & A. Yura &
E. Kadowaki & Y. Sato & J. S. Moon & K. Tomioka &
N. Okamoto & N. Kurumatani

Received: 26 November 2009 / Accepted: 1 March 2010 / Published online: 10 April 2010
# International Osteoporosis Foundation and National Osteoporosis Foundation 2010

Abstract
Summary Our cross-sectional analysis of 1,576 men aged
65 years examined smoking effects on bone status.
Number of smoking years was associated with decreased
bone mineral density (BMD), after adjusting for age,
height, weight, and number of cigarettes smoked daily.
Smoking did not affect biochemical marker serum values
for bone turnover.
Introduction The impact of smoking on bone status in men
has not been conclusively established. We examined how
smoking and its cessation influence bone status and
metabolism in men.
Methods We analyzed 1,576 men among a baseline survey of
Japanese men aged 65 years, the Fujiwara-kyo Osteoporosis
Risk in Men study, conducted during 20072008.
Results Lumbar spine (LS) BMD values among never,
former, and current smokers were 1.0450.194, 1.030

0.189, and 1.0010.182 g/cm2 (P=0.005), respectively,

while total hip (TH) BMD values were 0.8880.120,
0.8850.127, and 0.8700.124 (P=0.078), respectively.
The significant trend for LS BMD remained after adjusting
for the covariates; age, height, weight, physical activity, milk
consumption, and drinking habit (P=0.036). Among never
and ever (current and former) smokers, LS and TH BMD
decreased with the number of pack years or the number of
smoking years, respectively, adjusted for those covariates.
Among ever smokers, LS and TH BMD decreased with the
number of smoking years after adjusting for age, height,
weight, and number of cigarettes smoked daily. Smoking did
not reveal significant effect for serum osteocalcin or tartrate
resistant acid phosphatase isoenzyme 5b.
Conclusion The impact of smoking on bone status is
mainly associated with the number of smoking years in
elderly men.

J. Tamaki : M. Iki (*) : Y. Fujita : K. Kouda : A. Yura :

E. Kadowaki
Department of Public Health,
Kinki University School of Medicine,
377-2, Oono-higasi, Osaka-sayama,
Osaka 589-8511, Japan
e-mail: masa@med.kindai.ac.jp

Keywords Bone metabolism . Bone mineral density . Men .

Smoking

Y. Sato
Department of Human Life, Jin-ai University,
Echizen, Japan
J. S. Moon
Faculty of Human Sciences, Taisei Gakuin University,
Sakai, Japan
K. Tomioka : N. Okamoto : N. Kurumatani
Department of Community Health and Epidemiology,
Nara Medical University School of Medicine,
Kashihara, Japan

Introduction
Hip fractures is expected to increase throughout Asia and
Latin America by 2050, while the proportion of all hip
fractures among the elderly in Europe and North America
will fall from about one half to around one quarter by 2050
[1]. In Japan, 22% of all hip fractures occurred in men in
2002 [2]. Osteoporosis is now becoming a major public
health issue, even among men.
Smoking is associated with an increased risk for
osteoporosis [3, 4] and osteoporotic fractures [5]. Currently,
the smoking rate has decreased in developed countries, but

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has increased in developing countries including Asia [6].

This has contributed to the global tobacco epidemic as
reported by the World Health Organization in 2008 [6]. In
Japan, the smoking rate among men has continued to
decrease to approximately 40% [7], but this rate is still
higher than that of other developed countries [6].
Meta-analyses of the effects of smoking on bone status
have demonstrated decreased bone mass in current smokers
compared to non-smokers, although data for men is limited
[3, 4]. Ward et al. [4] reported that the decrease in bone
mass for smokers is greater in men than in women.
Additionally, smoking has more adverse effects on bone
mass for individuals aged 60 years or more [4]. A review
by Wong et al. [8] indicated that effects of smoking on bone
mass appears to be dose-dependent based on a metaanalysis [4]. However, this meta-analysis was conducted
without making distinctions between different smoking
characteristics such as the number of smoking years,
number of cigarettes smoked per day, and number of pack
years. Hence, more work is required to confirm which
smoking characteristic is adverse.
Regarding the effects of smoking on biochemical markers
of bone turnover, Compston [9] indicated that higher levels
of bone resorption in studies with older smokers and lower
levels of bone formation in studies with early postmenopausal women have been reported in smokers, though the
mechanisms have not been clearly established.
No large-scale study to date has focused on the effects of
smoking in Asian men, except for the Mr. OS study which
demonstrated that age- and weight-adjusted bone mineral
density (BMD) at the lumbar spine (LS) decreased with
increases in the number of pack years [10]. In Japan, the
relatively large osteoporosis or osteoporotic fracture studies
that included male participants are the Hiroshima cohort
study with atomic bomb survivors (male subjects, n=781),
and the Miyama cohort study (male subjects, n=166) [11];
neither has reported findings focused on the effects of
smoking on BMD. Thus, it would be valuable to ascertain
the impact of smoking or smoking cessation on bone status
and bone metabolism in elderly Japanese men. This is the
first large-scale Asian study to clarify relationships between
smoking and BMD in men. We analyzed a sample
population from a large-scale community-based singlecenter study for elderly Japanese men, the Fujiwara-kyo
Osteoporosis Risk in Men (FORMEN) study.

Osteoporos Int (2011) 22:133141

study, Fujiwara-kyo study (the Primary Investigator: Norio

Kurumatani, MD, PhD, Professor and Chairman, Department of Community Health and Epidemiology, Nara Medical
University School of Medicine), which was conducted as a
collaborative study with Nara Medical University and four
cities: Nara, Kashihara, Yamato-Koriyama, and Kashiba in
Nara Prefecture. Participants were recruited by the Administrative Center of the Fujiwara-kyo study, with the cooperation
of local resident associations and elderly peoples clubs
organized in each of the four cities. The present study briefly
explains the Fujiwara-kyo study. Details of the Fujiwara-kyo
study and the FORMEN study have been described elsewhere
[12]. The FORMEN study examined bone health of the male
participants of the Fujiwara-kyo study. Briefly, 2,012 men
aged 65 years or older who were participants in the
Fujiwara-kyo study completed the baseline survey during
20072008.
Study population
Of these 2,012 men, 347 were excluded due to a history of
illness and/or medication usage known to affect bone
metabolism (type 1 diabetes mellitus, uncontrolled hyperthyroid disease, parathyroid disease, connective tissue
disease, operated stomach cancer or ulcer, prostate cancer
with anti-androgen therapy, and oral glucocorticoid therapy
with 5 mg/day or more for a period of more than 3 months).
Among the remaining 1,665 men, 1,576 with complete
information on lifestyle factors, including smoking habits,
were included in the cross-sectional analysis.
The study protocol was approved by the Ethics Committee of the Kinki University School of Medicine and the
Medical Ethics Committee of the Nara Medical University.
Study procedures were explained to all participants and
written informed consent was obtained prior to participation
in the survey.
Baseline bone density characteristics

Methods

BMD was measured by dual X-ray absorptiometry at the

lumbar spine (L2-4) and total hip (QDR4500A, Hologic,
Bedford, MA, USA) [12, 13]. Short-term precision (coefficient of variance, CV) of BMD measurements in vivo was
1.2% for the LS and total hip (TH) [13]. We excluded from
the analysis densitometric data of the spine from participants
with vertebral fractures or grade four osteophytes according
to Nathan's classification [14], or those with hip deformities
in the regions of interest, as described elsewhere [12].

Study setting

Explanatory variables

The baseline survey for the FORMEN study was conducted

during 20072008 as part of a larger prospective cohort

Non-skeletal measures were obtained in the Fujiwara-kyo

study. Detailed information of the measurements is de-

Osteoporos Int (2011) 22:133141

135

scribed elsewhere [12]. We state briefly some measures

used in the present study.
Height and weight were measured using an automatic scale
(Tanita TBF-215, Tanita Inc., Japan). Body mass index (BMI)
was calculated as body weight (kilogram) divided by body
height squared (square meter). Variables assessed in the
surveys included smoking and drinking habits, milk consumption, past medical history, and medication history. Each
participant was interviewed by trained public health nurses,
nurses, or medical doctors. Regarding smoking history, both
current and former smokers were asked at what age they
began smoking, at what age they quit smoking (former
smokers), and the average number of cigarettes smoked daily.
Energy expenditure by daily physical activities was estimated
using an International Physical Activity Questionnaire [15]
validated in the Japanese elderly [16].

included adjustment for age, height, weight, energy consumption by daily physical activities, milk consumption, and
drinking habit. To accommodate multiple testing between
smoking status and characteristics, we used a Bonferroniadjusted test of significance. We rank-transformed the s-OC
data for the analysis because these data were not of a normal
distribution and values were presented as median values. To
reduce non-normality of distributions, s-TRACP-5b was log
transformed for the analysis and we presented the values as
geometric means with either a standard deviation or standard
error. The statistical significance was set at P<0.05.
Statistical analyses were performed with SPSS (version
14.0J; SPSS, Tokyo, Japan) or SAS system software for
personal computers (release 6.12; SAS Institute, Cary, NC,
USA).

Biochemical marker of bone turnover

Results

Fasting venous blood samples were drawn into serum

separator tubes from all subjects on their visits. The serum
was taken after a centrifugation under room temperature
and stored at 80C until it was assayed. We measured the
levels of biochemical markers of bone turnover; serum
osteocalcin (OC) and tartrate resistant acid phosphatase
isoenzyme 5b using commercially available kits according
to their manufacturers protocols.
OC (nanograms/milliliter) was measured by a two-site
immunoradiometric assay (BGP IRMA kit Mitsubishi,
Mitsubishi Kagaku Iatron Inc., Tokyo, Japan) with a
sensitivity of 1 ng/ml [17]. Intraassay, interassay, and
overall precision was represented by the CV determined
were 4.9%, 3.7%, and 6.1%, respectively.
TRACP-5b was measured by a fragment-absorbed
immunocapture enzyme assay (Osteolinks-TRAP-5b, Nitto
Boseki, Kooriyama, Japan) with a sensitivity of 19.2 mU/dl
[18]. The intraassay CV, interassay CV, and overall CV of
this measurement in our laboratory were 4.9%, 7.3%, and
8.8%, respectively.

Basic participant characteristics

Statistical analysis
We evaluated the effect of smoking status (never, former, and
current smokers) and smoking characteristics (number of
smoking years, number of pack years, number of cigarettes
smoked per day, and number of years since smoking cessation
for former smokers) on BMD values. Pack years were
calculated by multiplying the number of years smoked by
the number of cigarettes smoked per day and then dividing the
value by 20. Effects of confounding variables were adjusted
for using analysis of covariance when appropriate in
comparisons of the mean values of BMD between smoking
status, or between smoking characteristics. The analyses

Table 1 summarizes baseline data from the 1,576 study

participants according to smoking status. Proportions of
former smokers and current smokers were 59.2% and
17.6%, respectively. Age and BMI were found to be
significant variables among never, former, and current
smokers, and current smokers were significantly younger
and had significantly lower BMI values (Table 1). We
observed a significant decrease in LS BMD values from
never to former to current smokers (P value for trend test,
0.005), while we observed a marginal significant decrease
in TH BMD (P value for trend test, 0.078).
Smoking status and BMD
We observed a significant decrease in LS BMD values from
never to former to current smokers after adjusting for age,
height, weight, energy consumption by daily physical
activities, milk consumption, and alcohol drinking habits (P
value for trend test; 0.036; Table 2). LS BMD values were
significantly lower in current smokers compared to former
smokers after adjusting for the variables described above
through multiple comparisons. When current and former
smokers were combined as ever smokers, adjusted LS BMD
values were significantly lower in ever smokers than in never
smokers. TH BMD, s-OC, and s-TRACP-5b values did not
vary significantly by smoking status (Table 2).
Smoking exposure and BMD stratified by smoking
characteristics
Adjusted LS and TH BMD values were significantly and
negatively associated with number of smoking years or

23.1 (2.7)
1.029 (0.190)

BMI (kg/m2)

Lumbar spine BMD a (g/cm2)

15.1%
33.2%

One glass per 2-3 days

One glass or less weekly

9.2%
48.9%

3-5 times/week

6 or more times/week

No. cigarettes smoked per day

No. smoking years

No. pack years

34.4%

13.1%

44.3%
8.2%

30.9%

13.9%

9.3%
45.9%

170 (81, 378)

205.4 (1.7)

5.1 (3.3, 6.7)

0.888 (0.120)

1.045 (0.194)*

23.1 (2.7)

61.0 (8.2)

162.4 (5.3)

73.1 (5.1)#

Never smokers (n=366)

39.6 (29.3)

32.1 (13.8)

24.0 (14.4)

20.9 (3.6)

51.7%

8.8%

34.6%
4.9%

31.1%

15.9%

7.6%
45.4%

189 (84, 375)

210.0 (1.7)

4.9 (3.1, 6.4)

0.885 (0.127)

1.030 (0.189)

23.2 (2.7)*

61.8 (8.6)

163.1 (5.8)

73.6 (5.4)*

Former smokers (n=933)

41.7 (20.2)

49.2 (6.7)

17.1 (8.3)

21.0 (3.9)

58.5%

5.4%

32.9%
3.2%

46.6%

14.1%

5.8%
33.6%

180 (60, 410)

214.2 (1.8)

4.7 (3.4, 6.4)

0.870 (0.124)

1.001 (0.182)*

22.6 (3.0)*

59.7 (8.6)

162.5 (5.5)

71.5 (4.6)*,

Current smokers (n=277)

0.171

<0.001

<0.001

0.628

<0.001

<0.001

0.612

0.325

0.198

0.078

0.005

0.040

0.107

0.698

0.001

P valued

40.0 (27.5)

36.0 (14.4)

22.5 (13.6)

20.9 (3.7)

53.2%

8.0%

34.3%
4.5%

34.6%

15.5%

7.2%
42.7%

188 (79, 38.3)

211.0 (1.7)

4.8 (3.1, 6.4)

0.881 (0.126)

1.023 (0.188)

23.1 (2.8)

61.3 (8.6)

162.9 (5.7)

73.1 (5.3)

Ever smokerse (n=1,210)

<0.001

0.276

0.596

0.405

0.075

0.371

0.062

0.859

0.536

0.110

0.891

P valuef

P<0.05 with Bonferroni correction method by multiple comparisons between never, former,\ and current smokers for each line in the table

A t test, chi-squared test, or Mann-Whitney U test was performed between never and ever smokers

Ever smokers were former or current smokers

A trend test, the CochranArmitage trend test or the Kruskal-Wallis test was performed between never, former, and current smokers

Energy expenditure by level of daily physical activity was estimated using a physical activity questionnaire validated in Japanese elderly subjects [15]

*, #

b
Numbers of available participants were 1,535 (never smokers, 361; former smokers, 910; current smokers, 264) for osteocalcin, 1,564 (never smokers, 364; former smokers, 925; current smokers, 275) for
TRACP-5b, respectively

Data for BMD at the lumbar spine were obtained from 1,498 participants with neither deformities nor grade 4 osteophytes according to Nathans classification [14] at the second, third, or fourth lumbar
vertebrae

Each P value for osteocalcin was obtained after rank transformation, and each P value for TRACP-5b was obtained by using log-transformed values

BMI body mass index, BMD bone mineral density; TRACP-5b tartrate resistant acid phosphatase isoenzyme 5b

Values without % unit represent geometric means (standard deviation) for TRACP-5b, median (interquartile range) for osteocalcin and physical activity or mean (standard deviation) for other
characteristics

Age started smoking (years)

Smoking characteristics

36.5%
5.4%

Less than once/week

1-2 times/week

Alcohol drinking habit (%)

7.7%
43.5%

Two or more glasses daily

One glass daily

Milk consumption (%)

Physical activityc (kcal/day)

182 (79, 381)

209.7 (1.7)

Serum TRACP-5b (mU/dl)

Lifestyle characteristics

4.9 (3.2, 6.4)

Serum osteocalcin (ng/ml)

Biochemical marker of bone turnoverb

Total hip BMD (g/cm )

0.883 (0.125)

61.2 (8.5)

Weight (kg)

73.1 (5.2)
162.8 (5.7)

Age (years)

Height (cm)

Physical characteristics

Total (n=1,576)

Table 1 Baseline characteristics of participants stratified by smoking status in the FORMEN baseline study (20072008)

136
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Osteoporos Int (2011) 22:133141

137

Table 2 Bone mineral density and biochemical markers of bone turnover by smoking status in the FORMEN baseline study (20072008)
Never smokers (n=366)

Former smokers (n=933)

Current smokers (n=277)

P valueb

Ever smokersc (n=1,210)

P valueb

Lumbar spine BMD (g/cm2)

Age, height, and weight adjusted

1.047 (0.010)

1.024 (0.006)

1.020 (0.011)

0.085

1.023 (0.010)

0.028

Multivariate adjusteda

1.050 (0.010)

1.023 (0.006)*

1.019 (0.011)*

0.036

1.022 (0.005)

0.010

Total hip BMD (g/cm2)

Age, height, and weight adjusted

0.889 (0.006)

0.882 (0.004)

0.878 (0.007)

0.450

0.881 (0.003)

0.262

Multivariate adjusteda

0.892 (0.006)

0.881 (0.004)

0.878 (0.007)

0.209

0.880 (0.003)

0.084

Serum osteocalcin (ng/ml)

Age, height, and weight adjusted

5.0 (4.8, 5.1)

4.8 (4.6, 5.0)

4.8 (4.7, 5.0)

0.406

4.6 (4.8, 5.0)

0.056

Multivariate adjusteda

5.0 (4.7, 5.3)

4.8 (4.5, 5.1)

4.8 (4.6, 5.1)

0.969

4.8 (4.5, 5.1)

0.305

Serum TRACP-5b (mU/dl)

Age, height, and weight adjusted

205.38 (0.06)

210.05 (0.04)

214.21 (0.07)

0.404

210.99 (0.03)

0.390

Multivariate adjusteda

205.38 (0.06)

210.05 (0.04)

214.21 (0.07)

0.288

210.99 (0.03)

0.215

For use in the analysis of covariance, osteocalcin data were rank transformed and the TRACP-5b data were log transformed. Values in the table
represent mean (standard error) for BMD, median (interquartile range) for osteocalcin, or geometric mean (standard error) for TRACP-5b
BMD bone mineral density, TRACP-5b tartrate resistant acid phosphatase isoenzyme 5b
a

Values were adjusted for age, height, weight, dummy variables for each of the upper three quartiles of energy expenditure by daily physical activities with the
bottom quartile as a reference, for each level of milk consumption (two or more glasses daily, one glass daily, one glass per 2-3 days) with one glass or less weekly
as a reference, and for each level of alcohol drinking (1-2 times/week, 3-5 times/week, 6 or more times/week) with less than once/week as a reference

A trend test was performed between never, former, and current smokers, or between never and ever smokers

Ever smokers were former or current smokers

P<0.05 with Bonferroni correction by multiple comparisons between never, former, and current smokers for lumbar spine BMD

Table 3 BMD at the different skeletal sites by cigarette smoking characteristics among ever smokers compared with never smokers
Lumbar spine (N=1,498)
Distribution of
smoking
characteristics
n

Min

Max

Total hip (N=1,576)

Age-, height-,
and weightadjusted BMD

Multivariateadjustedb BMD

Distribution of
smoking
characteristics

Mean (SE)

Mean (SE)

1.047 (0.010)*

1.050 (0.010)*,

1.041 (0.009)

1.039 (0.009)

Min

Max

Age-, height-, and

weight-adjusted BMD

Multivariateadjustedb
BMD

Mean (SE)

Mean (SE)

Yeas of smoking
Never smokers

350

1st tertile of years of smoking

400

1.0

30.0

366
424

0.889 (0.006)
1.0

0.892 (0.006)

30.0

0.899 (0.005)*,
*

0.896 (0.005)*,

2nd tertile of years of smoking

347

30.1

45.0

1.010 (0.010)

1.010 (0.010)

360

30.1

45.0

0.873 (0.006)

3rd tertile of years of smoking

401

45.0

66.7

1.016 (0.009)

1.015 (0.009)#

426

45.0

68.0

0.870 (0.005)#

0.871 (0.005)#

0.003

0.001

<0.001

0.001

P valuea for trend

0.872 (0.006)

Cigarettes smoked per day

Never smokers

350

1.047 (0.010)

1.050 (0.010)*

366

0.889 (0.006)

0.892 (0.006)

1st tertile of cigarettes smoked per day

388

15

1.022 (0.009)

1.019 (0.009)

409

15

0.883 (0.006)

0.879 (0.006)

2nd tertile of cigarettes smoked per day

418

16

20

1.031 (0.009)

1.031 (0.009)

440

16

20

0.879 (0.005)

0.881 (0.005)

3rd tertile of cigarettes smoked per day

342

22

100

1.014 (0.010)

1.013 (0.010)*

361

22

100

0.881 (0.006)

0.881 (0.006)

0.037

0.023

0.325

0.233

P valuea for trend

Pack years
Never smokers

350

1.047 (0.010)

1.050 (0.010)*

366

0.889 (0.006)

0.892 (0.006)

1st tertile of pack years

389

0.5

25.0

1.036 (0.009)

1.034 (0.009)

397

0.5

24.6

0.894 (0.006)

0.891 (0.006)

2nd tertile of pack years

376

25.2

45.9

1.019 (0.009)

1.017 (0.009)

410

25.0

46.0

0.874 (0.006)

0.872 (0.005)

3rd tertile of pack years

383

46.0

192.0

1.014 (0.009)

1.015 (0.009)*

403

46.1

192.0

0.875 (0.006)

0.877 (0.006)

0.047

0.027

0.028

0.026

P value a for trend

BMD bone mineral density

a

A trend test was performed between never and ever smokers

BMD was adjusted for age, height, weight, dummy variables for each of the upper three quartiles of energy expenditure by daily physical activities with the
bottom quartile as a reference, for each level of milk consumption (two or more glasses daily, one glass daily, one glass per 2-3 days) with one glass or less weekly
as a reference, and for each level of alcohol drinking (1-2 times/week, 3-5 times/week, 6 or more times/week) with less than once/week as a reference

*, #

P<0.05 with Bonferroni correction method by multiple comparisons between never and ever smokers for each column in the table

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Osteoporos Int (2011) 22:133141

Table 4 BMD at the different skeletal sites by cigarette smoking characteristics among former smokers compared with never smokers
Lumbar spine (N=1,234)

Total hip (N=1,299)

Distribution of
smoking
characteristics

Age, height, weightadjusted BMD

Multivariateadjustedb BMD

Distribution of
smoking
characteristics

Age, height, weightadjusted BMD

Multivariateadjustedb BMD

Mean (SE)

Mean (SE)

Mean (SE)

Mean (SE)

Min Max

Min Max

Yeas of smoking
Never smokers
1st tertile of years of
smoking
2nd tertile of years of
smoking
3rd tertile of years of
smoking
P value a for trend

350

1.051 (0.010)*

1.054 (0.010)*

366

309

1.054 (0.010)#

325

1.0

25.0 1.056 (0.010)

300 26.0

40.0 1.007 (0.010)*,

275 41.0

62.0 1.018 (0.011)

0.001

1.006 (0.010)*,
1.019 (0.011)

0.890 (0.006)

0.893 (0.006)

1.0

25.0 0.907 (0.006)*,

316 26.0

40.0 0.874 (0.006)*

0.872 (0.006)*

292 41.0

68.0 0.868 (0.007)#

0.870 (0.007)#

0.001

<0.001

0.905 (0.006)*,

<0.001

Cigarettes smoked per day

Never smokers

350

1st tertile of cigarettes

smoked per day
2nd tertile of cigarettes
smoked per day
3rd tertile of cigarettes
smoked per day
P value a for trend

262

1.051 (0.010)

1.054 (0.010)

366

0.890 (0.006)

0.893 (0.006)

18

1.021 (0.011)

1.017 (0.011)

278

18

0.885 (0.007)

0.881 (0.007)

327 20

22

1.042 (0.010)

1.043 (0.010)

344 20

24

0.881 (0.006)

0.883 (0.006)

295 23

100

1.018 (0.011)

1.018 (0.011)

311 25

100

0.886 (0.006)

0.885 (0.006)

0.092

0.074

0.541

0.448

Pack years
Never smokers

350

1.051 (0.010)

1.054 (0.010)

366

0.890 (0.006)

0.893 (0.006)

1st tertile of pack years

294

0.5

22.5 1.044 (0.011)

1.041 (0.011)

314

0.5

22.5 0.899 (0.006)

0.895 (0.006)

2nd tertile of pack years

303 23.0

45.0 1.022 (0.010)

1.021 (0.010)

314 23.0

45.0 0.878 (0.006)

0.876 (0.006)

3rd tertile of pack years

287 45.1 192.0 1.018 (0.011)

1.019 (0.011)

305 45.1 192.0 0.875 (0.006)

0.877 (0.006)

P valuea for trend

0.056

0.049

0.028

0.047

BMD bone mineral density

a

A trend test was performed between never and former smokers

BMD was adjusted for age, height, weight, dummy variables for each of the upper three quartiles of energy expenditure by daily physical activities with the
bottom quartile as a reference, for each level of milk consumption (two or more glasses daily, one glass daily, one glass per 2-3 days) with one glass or less weekly
as a reference, and for each level of alcohol drinking (1-2 times/week, 3-5 times/week, 6 or more times/week) with less than once/week as a reference

*, #

P<0.05 with Bonferroni correction method by multiple comparisons between never and ever smokers for each column in the table

number of pack years, respectively, in both never and ever

smokers (Table 3). Adjusted LS BMD values in subjects in
the third tertile of cigarettes smoked per day (22/day) were
significantly lower than those in never smokers (1.050 [SE;
0.010] vs. 1.013 [SE; 0.010], P<0.05 with Bonferroni
correction method), as shown in Table 3. A similar analysis
as was done for Table 3 revealed that for every smokers, we
observed a significant and negative association between
number of smoking years and LS and TH BMD (P value for
trend test; 0.007 and 0.008, respectively), after adjusting for
age, height, weight, and number of cigarettes smoked per
day. Number of smoking years was categorized by tertile
values in the same manner as was done in Table 3. The
significant association between number of smoking years
and TH BMD remained after we adjusted for the variables
used in the model in Table 3 (P value for trend test, 0.045).
Among current smokers, neither number of smoking
years, number of cigarettes smoked per day, nor number of

pack years was significantly associated with BMD values

(data not shown).
Among never and former smokers, LS and TH BMD
values were significantly associated with number of
smoking years, but not with number of cigarettes smoked
per day (Table 4). The number of pack years was
associated with decreased LS and TH BMD values with
marginal significance (Table 4). A similar analysis as was
done for Table 4 revealed that for former smokers, number
of smoking years was significantly and negatively associated with LS and TH BMD values (P value for trend test;
0.004 and <0.001, respectively). No statistically significant associations were observed between the number of
pack years and LS and TH BMD value among former
smokers (data not shown). The correlation coefficient
between the number of smoking years and number of
years since smoking cessation was 0.892 (P<0.001) in
former smokers.

Osteoporos Int (2011) 22:133141

139

Table 5 Biochemical markers of bone turnover by cigarette smoking characteristics among never and current smokers
Serum osteocalcin (ng/ml)

Serum TRACP-5b (mU/dl)

Age, height, weight-adjusted

Multivariate-adjustede

5.0 (4.7, 5.3)

205.38 (0.06)

205.38 (0.06)

4.6 (4.2, 4.9)

202.31 (0.10)

202.31 (0.10)

5.0 (4.9, 5.2)

5.0 (4.7, 5.4)

227.30 (0.10)

227.30 (0.10)

0.935

0.473

0.226

0.222

Never smoker

5.0 (4.8, 5.1)

5.0 (4.7, 5.3)

205.4 (0.1)

205.4 (0.1)

Cigarettes smoked per day<median

4.9 (4.7, 5.1)

4.9 (4.6, 5.3)

223.1 (0.1)

223.1 (0.1)

Cigarettes smoked per daymedian

4.7 (4.6, 4.8)

4.7 (4.3, 5.1)

206.1 (0.1)

206.1 (0.1)

0.463

0.832

0.898

0.822

Never smoker

5.0 (4.8, 5.1)

5.0 (4.7, 5.3)

205.4 (0.1)

205.4 (0.1)

Pack years<median

4.9 (4.7, 5.0)

4.9 (4.6, 5.2)

221.8 (0.1)

221.8 (0.1)

Pack yearsmedian

4.7 (4.6, 4.9)

4.8 (4.4, 5.1)

206.9 (0.1)

206.9 (0.1)

0.557

0.621

0.998

0.884

Age, height, weight-adjusted

Multivariate-adjusted

Never smoker

5.0 (4.8, 5.1)

Years of smoking<median

4.6 (4.5, 4.7)

Years of smokingmedian

Years of smokinga

P valueb for trend

Cigarettes smoked per dayc

P valueb for trend

Pack yearsd

P valueb for trend

For use in the analysis of covariance, osteocalcin data were rank transformed, and the TRACP-5b data were log transformed. Values in the table
represent median (interquartile range) for osteocalcin, and geometric mean (standard error) for TRACP-5b. Numbers of available participants were
never smokers, 361; current smokers, 264 for osteocalcin, never smokers, 364; current smokers, 275 for TRACP-5b, respectively.
a

The median value: 49.2

A trend test was performed between never and current smokers.

The median value: 17

The median value: 40.2

Values were adjusted for age, height, weight, dummy variables for each of the upper three quartiles of energy expenditure by daily physical activities with
the bottom quartile as a reference, for each level of milk consumption (two or more glasses daily, one glass daily, one glass per 2-3 days) with one glass or
less weekly as a reference, and for each level of alcohol drinking (1-2 times/week, 3-5 times/week, 6 or more times/week) with less than once/week as a
reference

Smoking status, smoking characteristics, and biochemical

markers of bone turnover
Serum OC or TRACP-5b values did not differ significantly by
smoking characteristics (Table 5). When stratified by smoking characteristics, these same values did not vary between
never smokers, current smokers, current smokers with 20 or
fewer cigarettes smoked per day, and current smokers with
more than 20 cigarettes smoke per day (data not shown),
though we indicated in Table 3 that ever smokers with more
than 20 cigarettes smoked per day had significantly higher
LS BMD values compared to never smokers.

Discussion
This study provides evidence that smoking status is
associated with decreased BMD in men aged 65 years or
older in large-scale community-based single-center study
elderly Japanese men, the FORMEN baseline study.
Regarding smoking characteristics, the number of pack
years, and more significantly, the number of smoking years
were associated with decreased BMD. The number of

cigarettes smoked per day was only associated with a

reduction in LS BMD among ever smokers and never
smokers. A strength of this study was that it is a populationbased study with a relatively large sample size of Asian
men following the Mr. OS study [10].
Findings of this study are consistent with those from two
meta-analyses [3, 4], which revealed that the bone mass of
current smokers was lower than that of never and former
smokers. We revealed significant trends for LS BMD, but
not for TH BMD, among three (never, former, current)
smoking status groups, which findings are consistent with
findings by Ward et al. [4].
Previous studies classifying men by smoking characteristics have shown a decrease in bone mass with the number
of smoking years [1924] and pack years [10, 20, 2530],
which was consistent with our findings. Regarding the
number of cigarettes smoked per day, results with men have
shown inconsistent positive [22, 23, 25, 31] and negative
findings [24, 32]. Smokers with 20 or more cigarettes per
day generally revealed significant lower BMD compared
with that in never smokers [22, 23, 25], which was
consistent with our findings. Negative findings could be
due to a relatively small numbers of subjects (total of 222

140

male) [32], or low numbers of cigarettes per day (mean

values; 12 cigarettes per day among smokers) [24].
Regarding the effects of smoking cessation, Wong et al. [8]
indicated that there was insufficient data to determine the
number of years since smoking cessation necessary for a
meaningful biological effect in the meta-analysis [3, 4].
However, we could not analyze the effects of the number of
years since smoking cessation, as the numbers of smoking
year and years since smoking cessation were highly correlated.
Concerning a novel bone resorption marker; TRACP-5b,
we had no comparable data, while Supervia et al [33] reported
no effect of smoking on serum TRACP which was not a
specific marker for an osteoclast activity. With regard to the
effect of smoking on other bone resorption markers, the data
were also scare and discordant. In male smoker with low
body weight, bone resorption marker (C-terminal telopeptide, free and total deoxypyridinoline) was increased [34].
No difference of urinary hydroxyproline among men [25] or
urinary N-telopeptiode (NTX) among men [33] were
reported, while an increase of u-NTX was seen in female
smokers [9]. Our findings about TRACP-5b, which has a
low diurnal variability and is not affected by feeding [35]
and did not vary significantly with age among Japanese men
[36], would indicate that the current smoking does not affect
osteoclast activities. A review about biochemical markers of
bone turnover in men by Szulc et al [37] indicated an
apparent stability of the levels of bone markers in better
health status. As long as we know, there was no available
data of smoking effect on s-OC in elderly men, while there
were no different values of serum osteocalcin between
smokers and non-smokers in studies with young men [25,
33]. Further studies about the effects of smoking on bone
formation and resorption should be conducted.
Our finding revealed a significant effect of smoking
characteristic on LS and TH BMD. Although LS BMD in
the elderly is well known to present measurement difficulties due to deformities or aortic calcifications and is
affected by these artifacts, a significant difference was
observed. This finding is consistent with previous studies
[4, 10, 23]. The underlying mechanism of the adverse
smoking effect remains unclear, but one speculation on why
LS BMD values were affected by smoking is that the peak
bone mass at LS is achieved later than that of TH [38],
while the majority of peak bone mass at TH would be
achieved during adolescence [38, 39]. This suggests that
TH bone mass could be achieved before smoking initiation.
Thus, the smoking effect on LS BMD might be seen even
when values for the signal-to-noise ratio of LS BMD are
lower than those of TH BMD.
There are several limitations to the present study. First,
the study participants are volunteers, not a random sample
of the general population. It has been reported that
volunteers involved in research studies tend to be better

Osteoporos Int (2011) 22:133141

educated and slightly less likely to smoke than the general

population [40]. The participants in our study also revealed
a lower current smoking rate, but a higher former rate than
Japanese men in the general population [7]. However, we
have focused on the effect of smoking on bone status
among healthy elderly male subjects who live independently in community as few studies have been conducted with
those subjects. Second, the cross-sectional design of the
study fails to establish causality between smoking and
reduced bone density. Future follow-up studies will clarify
smoking effects on changes in BMD and osteoporotic
fractures. Finally, data regarding smoking exposure was
entirely self-reported. However, trained public health nurses
or medical doctors conducted all interviews. There might be
an information bias regarding smoking exposure, some
might answer less number or years of cigarettes smoked, as
it causes underestimation of the smoking effect.
Our findings obtained by the FORMEN study confirm
the deleterious effects of smoking on bone status. The
number of smoking years, rather than the number of
cigarettes smoked per day, is mainly associated with
decreased BMD in elderly male subjects living independently in a community. Bone metabolism among current
smokers, as measured by biochemical markers, was not
significantly different from that among never smokers. Our
findings should be utilized to identify a strategy to promote
bone health in elderly men.
Acknowledgments Financial support for the baseline survey was
provided by St. Lukes Life Science Institute Grant-in-Aid for
Epidemiological Research, Foundation for Total Health Promotion, a
Grand-in-Aid for study on Milk Nutrition (2008) from the Japan Dairy
Association, a Grant (2008) from Physical Fitness Research Institute,
MEIJI YASUDA Life Foundation of Health and Welfare, Grants-inaid for Scientific Research (#20659103: 2008-2009, B #21390210:
2009-2011, C #20590661: 20082010), and Grant-in-Aid for Young
Scientists ( B #20790451: 2008-2010) from the Japanese Ministry of
Education, Culture, Sports, Science and Technology.
Conflicts of interest None.

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