Osteoporosis International

, Volume 17, Issue 4, pp 627–633

Body composition and vertebral fracture risk in female patients treated with glucocorticoid

Authors

    • Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular MedicineKobe University Graduate School of Medicine
  • T. Tobimatsu
    • Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular MedicineKobe University Graduate School of Medicine
  • J. Naito
    • Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular MedicineKobe University Graduate School of Medicine
  • M.-F. Iu
    • Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular MedicineKobe University Graduate School of Medicine
  • M. Yamauchi
    • Division of Endocrinology/Metabolism and Hematological OncologyShimane University School of Medicine
  • T. Sugimoto
    • Division of Endocrinology/Metabolism and Hematological OncologyShimane University School of Medicine
  • K. Chihara
    • Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular MedicineKobe University Graduate School of Medicine
Original Article

DOI: 10.1007/s00198-005-0026-5

Cite this article as:
Kaji, H., Tobimatsu, T., Naito, J. et al. Osteoporos Int (2006) 17: 627. doi:10.1007/s00198-005-0026-5

Abstract

Introduction

Glucocorticoid (GC) causes bone loss and an increase in bone fragility. However, fracture risk was found to be only partly explained by bone mineral density in GC-treated patients (GC patients). Although GC causes a change in the distribution of fat in the body, the relationship between body composition and fracture risk in GC patients remains unknown.

Methods

The present study examined the relationship between the presence or absence of vertebral fractures and various indices, including body composition, in 92 premenopausal GC patients, 122 postmenopausal GC patients and 122 postmenopausal age-matched control subjects. Dual-energy X-ray absorptiometry was employed to analyze body composition.

Results

Percentage lean body mass (LBM), % fat and % trunk fat were not significantly different between postmenopausal GC patients and the control women. When groups with and without vertebral fractures were compared, % LBM and % fat were significantly higher and lower in groups with vertebral fractures, respectively, in postmenopausal GC patients, but not in the postmenopausal control women, although % trunk fat was not significantly different between groups with and without vertebral fractures. Femoral neck BMD was negatively correlated with % LBM and positively correlated with % fat. In premenopausal GC patients, % trunk fat was significantly higher in the fracture group, although % LBM and % fat were not significantly different between groups with and without vertebral fractures.

Conclusion

The present study revealed that body composition is related to vertebral fracture risk in GC-treated patients. Lower % fat can be included in the determination of vertebral fractures in postmenopausal GC-treated patients. The influence of body composition on vertebral fracture risk may be different between the pre- and postmenopausal state in GC patients.

Keywords

Body compositionFractureGlucocorticoidOsteoporosis

Introduction

Glucocorticoid (GC) is used for the treatment of a number of serious diseases, including rheumatic, collagen and respiratory diseases. GC-induced osteoporosis (GIO) is a major problem for patients undergoing GC therapy, and many GIO patients suffer from decreases in activity of daily life and quality of life. About 50% of the patients with Cushing syndrome and 30–50% of the patients on long-term GC therapy have atraumatic fractures due to osteopenia [1, 2]. It can therefore be concluded that GC causes bone loss and an increase in bone fragility, resulting in a large increase in fracture risk. Van Staa et al. [3] reported that the relative risk of nonvertebral fractures during oral GC treatment was 1.33, that of hip fractures, 1.61, that of forearm fractures, 1.09, and that of vertebral fractures, 2.60. Other studies have also confirmed the increased risk of vertebral and hip fractures in patients with GIO [2, 47]. While lower bone mineral density (BMD) has been found in the hip and vertebrae of patients taking GC orally [812], a meta-analysis of prior GC use and fracture risk suggested that fracture risk was only partly explained by BMD [4], and Peel et al. [13] found that lumbar BMD could not be used to predict the risk of vertebral fractures. Moreover, controversies exist about the threshold of BMD in patients with GIO [14, 15]. As a result, factors other than BMD are now considered to affect fracture risk in GC-treated patients.

Several reports have been published on the risk factors for fractures in GIO. Age has been found to be an important and independent risk factor for vertebral deformity in patients taking long-term GC therapy [16]. Steinbuch et al. [4] found that a long-term and continuous pattern of GC use resulted in a significant fivefold increased risk of hip fracture and a 5.9-fold increased risk of vertebral fracture. Although GC causes the distribution of fat to be altered in the body, such as central obesity, and while both lean body mass (LBM) as well as fat mass influence BMD [1719], the relationship between body composition and fracture risk in GC-treated patients remains unclear.

Dual-energy X-ray absorptiometry (DXA) has enabled body composition in terms of LBM and fat mass to be analyzed easily and precisely [20]. The objective of the study reported here was, therefore, to use this technology to examine the relationship between the presence or absence of vertebral fractures and various indices, including body composition, in 214 female patients receiving oral GC treatments because of collagen, neurological, dermatological or respiratory diseases. We also analyzed the factors related to the risk of vertebral fractures.

Subjects and Methods

Subjects

Two hundred and fourteen female patients who were being treated with oral GC for more than 6 months (GC patients) and 122 age-matched postmenopausal control subjects participated in this study. Among the GC patients, 92 and 122 patients were premenopausal and postmenopausal, respectively. Basal diseases of GC-treated patients are shown in Table 1. We excluded those subjects whose activity of daily life was already disturbed. Among the 214 patients, 167 (78%) had autoimmune diseases. The control subjects were Japanese postmenopausal women who had visited our outpatient clinic in order to determine whether or not they might suffer from osteoporosis. They were age-matched with postmenopausal GC patients. The study was approved by the ethical review board of Kobe University Hospital. All subjects agreed to participate in the study and gave informed consent.
Table 1

Basal diseases of GC patients

 

Premenopause

Postmenopause

Autoimmume diseases

83 (SLE 56, PM 6, RA 5, MCTD 5)

87 (SLE 19, PM 14, RA 21, MCTD 10)

Neurological diseases

3 (MG 1, MS 1)

16 (MG 11, MS 5)

Dermatological diseases

0

6

Respiratory diseases

2

9

Inflamatory bowel diseases

2

1

Hematological diseases

2

3

Total

92

122

SLE: systematic lupus erythematosis; PM: polymyositis; MCTD: mixed connective tissue disease; RA: rheumatoid arthritis; MG: myathenia gravis; MS: multiple sclerosis

Biochemical measurements

Blood and urine samples were collected after an overnight fast. Urine samples were obtained from the first void urine. Routine serum and urinary chemistry determinations were performed by standard automated techniques. Serum concentrations of intact parathyroid hormone (PTH) were measured by immunoradiometric assay (Allegro Intact PTH IRMA kit; Nichols Institute Diagnostics, San Juan Capistrano, Calif.; normal range: 10–65 ng/l), as previously described [21]. Serum levels of osteocalcin and urinary levels of deoxypyridinoline (Dpd) were measured as previously described [22].

Radiography

Lateral radiographs of the thoracic and lumbar spine were taken. The anterior, central and posterior heights of each of the 13 vertebral bodies from T4 to L4 were measured using an electronic caliper. Vertebral fractures were diagnosed to be present if at least one of three height measurements taken from along the length of the same vertebra was decreased by more than 20% compared with the height of the nearest uncompressed vertebral body. Based on this criterion, 50 women (8 and 42 for premenopausal and postmenopausal women, respectively) in the GC group and 22 women in the control group were diagnosed as having one or more vertebral fractures. Defining vertebral fracture from radiographs of the lumbar spine is difficult because there is no gold standard for what types of deformities of vertebral shape are the results of bone breakage. Definitions of vertebral fractures with high true positive rates and low false positive rates are clinically useful in identifying women who may have vertebral fractures. The criterion in the present study (>20%) was considered to be good for defining vertebral fractures because it had a relatively high true positive rate and low false positive rate based on qualitative classifications from a previous report [23].

BMD measurements by DXA

BMD values were measured by DXA using QDR-2000 (Hologic Inc., Waltham, Mass.) at the lumbar spine (L2-4), femoral neck (FN) and distal one-third of radius (Rad1/3). BMD was automatically calculated from the bone area (in square centimeters) and bone mineral content (BMC) (in grams) and expressed absolutely in grams per square centimeter. The Z-score is the number of standard deviations (SD) a given measurement differs from the mean for a sex-, age- and race-matched reference population. The T-score is the number of SD a given measurement differs from the mean for a normal young adult reference population. The coefficients of variation (precision) of measurements of the lumbar spine, femoral neck and radius were 0.9, 1.7 and 1.9%, respectively. The coefficient of variation was obtained in vitro using ‘phantom’ with at least four time measurements for the same subject. Normative data were obtained from a population-based database for the Japanese Society of Bone and Mineral Research established in 1996.

Measurement of body composition

BMC, LBM and fat mass were measured by DXA (QDR-2000; Hologic Inc.) using whole-body absorptiometry software and was expressed in kilograms. Percentages of BMC, LBM and fat mass were calculated by dividing each absolute value of body composition by total body mass. Percentage trunk fat was calculated by dividing trunk fat mass by total fat mass and was designated percentage (%) trunk fat. The same operator tested all of the women during the study in order to eliminate operator discrepancies. A strong correlation between body weight and total body mass measured by DXA (r=0.98) was obtained in a preliminary study. The coefficients of variation of measurements of BMC, LBM and fat mass were 0.9, 1.0 and 2.0%, respectively. The coefficient of variation was obtained in vitro using ‘phantom’.

Statistical analysis

All data were expressed as the mean ± SD for each index. A regression analysis was performed using the statistical computer program Abacus Concepts StatView (Abacus Concepts, Inc., Berkeley, Calif.). Comparisons of each group were made with the nonparametric Mann-Whitney U-test. Univariate or multiple logistic regression analyses were performed to evaluate association between various indices and vertebral fractures. p values <0.05 were considered to be significant.

Results

Background data

Baseline indices are shown in Table 2 in premenopausal and postmenopausal GC patients as well as postmenopausal women of the control group. The incidences of vertebral fractures were 8.7, 34.4 and 18.0% in premenopausal GC patients, postmenopausal GC patients and postmenopausal women of the control group, respectively. Body height, body weight and the body mass index (BMI) were similar in both postmenopausal groups. BMD at any site was also similar in both postmenopausal groups. When Rad1/3 BMD was analyzed by excluding patients with rheumatoid arthritis, Rad1/3 BMD was 0.675±0.074 and 0.554±0.091 g/cm2 for premenopausal and postmenopausal GC patients, respectively. With respect to premenopausal women, the serum level of non-specific alkaline phosphatase (ALP) at any one site was significantly higher in postmenopausal patients and the BMD at any one site was significantly lower. These results appeared to be due to both age and menopause. Table 3 presents a comparison of the body composition indices (% BMC, % LBM, % fat and % trunk fat) of the three groups. There were no significant differences with respect to any of these four indices between the postmenopausal GC patients and the postmenopausal control women; however, relative to postmenopausal GC patients, % BMC was significantly higher in the premenopausal GC patients and % trunk fat was significantly lower patients than in the postmenopausal GC patients.
Table 2

Background data in the control and GC-treated groups

 

Premenopausal GC patients

Postmenopausal GC patients

Postmenopausal control women

Number of subjects

92

122

122

Number of subjects with vertebral fracture

8

42

22

Age (years)

34.4±9.3*

61.0±9.1

60.9±9.1

Body height (cm)

158.1±6.4*

152.5±10.9

153.4±5.9

Body weight (kg)

54.5±9.3*

50.6±10.9

52.0±7.8

BMI (kg/m2)

21.8±3.2

21.7±3.2

22.1±3.0

ALP (IU/l)

168.0±56.0*

238.8±82.4

243.0±82.4

PTH (pg/ml)

30.9±12.8*

37.5±15.7

41.3±14.5

L2-4BMD (g/cm2)

0.929±0.141*

0.823±0.158

0.801±0.154

FN BMD (g/cm2)

0.714±0.119*

0.598±0.106

0.618±0.106

FN BMD (T score)

−0.644±1.130*

−1.750±1.008

−1.559±1.006

Rad1/3 BMD (g/cm2)

0.675±0.073*

0.534±0.102

0.535±0.078

*p<0.01, **p<0.05. Compared with post menopausal GC patients

Table 3

Body composition in control and GC-treated groups

 

Premenopausal GC patients

Postmenopausal GC patients

Postmenopausal control women

% BMC

3.6±0.6*

2.9±0.5

3.0±0.6

% LBM

61.7±7.3

63.2±9.0

61.6±7.2

% Fat

34.6±7.7

33.8±9.1

35.4±7.7

% Trunk fat

39.2±7.2*

44.3±8.9

45.4±7.9

*p<0.01. Compared with post menopausal GC patients

Comparison of various indices between groups with and without vertebral fractures in postmenopausal GC patients and control subjects

We compared various indices between postmenopausal patients taking oral GC with and without vertebral fractures. As shown in Table 4, age was higher in the fracture group. Body size index (body height, body weight and BMI) was significantly lower in the group with vertebral fractures and urinary level of Dpd was significantly higher. BMD at any site was lower in the fracture group. When Rad1/3 BMD was analyzed by excluding patients with rheumatoid arthritis, Rad1/3 BMD was 0.535±0.106 and 0.562±0.083 g/cm2 (p=0.2370) for patients with and without vertebral fractures, respectively; thus, the significant difference between groups with and without fractures disappeared. The current dose of GC was 10.7±7.6 and 8.9±7.7 mg for groups with and without vertebral fractures, respectively; the maximum dose of GC was 31.3±21.0 and 34.8±17.7 mg for groups with and without vertebral fractures, respectively. On the other hand, in postmenopausal control subjects, body size indices were not significantly different between groups with and without fractures, although age was higher in the fracture group and BMD was lower.
Table 4

Comparison of various indices between postmenopausal control women and GC patients with (+) and without (−) vertebral fractures

 

GC-treated

p

Control

p

fracture (−)

fracture (+)

fracture (−)

fracture (+)

Age (years)

59.5±8.7

63.9±9.2

0.0131**

59.1±8.6

67.3±7.8

0.0002*

Body height (cm)

153.5±5.6

150.5±6.5

0.0220**

153.8±6.0

152.9±5.6

0.4874

Body weight (kg)

52.7±6.9

46.5±9.2

0.0001*

52.0±8.0

52.8±7.3

0.7245

BMI (kg/m2)

22.4±2.8

20.5±3.59

0.0021**

22.0±3.0

22.6±3.3

0.3581

L2-4BMD (g/cm2)

0.844±0.144

0.780±0.176

0.0001*

0.820±0.154

0.733±0.131

0.0030*

FN BMD (g/cm2)

0.620±0.094

0.556±0.116

0.0006*

0.632±0.106

0.567±0.090

0.0056*

Rad1/3 BMD (G/cm2)

0.551±0.088

0.501±0.119

0.0215**

0.547±0.075

0.490±0.076

0.0016

ALP (IU/I)

225.8±69.2

266.7±100.7

0.0527

236.1±72.9

270.4±114.5

0.3991

intact PTH (pg/ml)

36.2±13.9

40.1±18.9

0.5307

42.1±14.4

38.3±15.4

0.3328

Osteocalcin (μg/dl)

5.5±3.1

4.5±3.1

0.0994

   

U-Dpd (nmol/mmol Cr)

7.1±3.4

9.9±5.2

0.0093*

   

*p<0.01, **p<0.05

With respect to body composition, % LBM was significantly higher and % fat was significantly lower in the group with vertebral fractures in the postmenopausal GC patients, but not in the postmenopausal control women (Table 5). Percentage trunk fat was not significantly different between groups with and without vertebral fractures in the postmenopausal GC patients and control women.
Table 5

Body composition in control and GC-treated groups with (+) and without (−) vertebral fractures

 

Premenopausal GC patients

Postmenopausal GC patients

Postmenopausal control women

Fracture

(−)

(+)

(−)

(+)

(−)

(+)

% BMC

3.7±0.5

2.9±0.3*

3.0±0.5

2.8±0.5**

3.1±0.6

2.7±0.5*

% LBM

61.8±7.5

60.2±4.5

61.6±7.5

66.2±10.6**

61.6±7.3

61.4±7.3

% Fat

34.4±7.9

36.9±4.6

35.2±7.8

31.0±10.9**

35.4±7.9

36.0±7.6

% Trunk fat

38.4±6.7

47.0±7.7

44.8±7.9

43.3±10.5

45.0±8.2

47.9±6.8

*p<0.01, **p<0.05

Comparison of various indices between groups with and without vertebral fractures in premenopausal GC patients

We subsequently compared various indices between premenopausal patients taking oral GC with and without vertebral fractures. As shown in Table 6, women of the fracture group were older than those in the non-fracture group. Body height and BMD at any site were significantly lower in the group with vertebral fractures. When Rad1/3 BMD was analyzed by excluding patients with rheumatoid arthritis, the Rad1/3 BMD was 0.569±0.082 and 0.686±0.065 g/cm2 (p=0.0006) for patients with and without vertebral fractures, respectively. Bone metabolic indices, body weight, BMI and current and maximum doses of GC were not significantly different between groups with and without fractures. As for body composition, % trunk fat was significantly higher in the fracture group, although % LBM and % fat were not significantly different between groups with and without vertebral fractures (Table 5).
Table 6

Comparison of various indices between premenopausal GC patients with (+) and without (−) vertebral fractures

 

Vertebral fractures

p

(−)

(+)

Age (years)

33.4±9.0

42.1±8.8

0.0129**

Body height (cm)

158.7±6.2

152.4±5.2

0.0092*

Body weight (kg)

54.9±9.5

50.0±4.4

0.0883

BMI (kg/m2)

21.8±3.2

21.7±3.4

0.8030

L2-4BMD (g/cm2)

0.945±0.133

0.751±0.097

0.0002*

FN BMD (g/cm2)

0.728±0.112

0.570±0.098

0.0003*

Rad1/3 BMD (g/cm2)

0.685±0.064

0.569±0.082

0.0006*

ALP (IU/I)

165.9±55.6

191.9±59.6

0.1900

intact PTH (pg/ml)

31.3±12.6

27.6±14.8

0.2292

Osteocalcin (μg/dl)

3.41±1.76

3.44±1.72

0.8813

u-Dpd (nmol/mmol Cr)

6.05±5.51

7.64±4.46

0.1535

Current dose of GC (mg/day)

9.9±6.3

7.5±3.0

0.1019

Maximum dose of GC (mg/day)

42.9±17.2

53.3±16.3

0.4216

*p<0.01, **p<0.05

Correlations between body composition and other indices in postmenopausal GC-treated patients

We calculated correlations between body composition and other indices in postmenopausal GC-treated patients to examine the relationship between fat and vertebral fractures. As shown in Table 7, FN BMD was negatively correlated with % LBM and positively correlated with % fat.
Table 7

Correlations between body composition and other indices in postmenopausal GC patients

 

% BMC

% LBM

% Fat

% Trunk fat

Age

−0.311*

0.128

−0.147

−0.074

L2-4BMD

0.410*

−0.168

0.177

−0.003

FN BMD

0.415*

−0.315*

0.334*

0.163

Rad1/3 BMD

0.620*

−0.164

0.145

0.020

Albumin

−0.102

−0.184

0.174

−0.353

ALP

−0.282*

−0.004

0.015

−0.214

intact PTH

−0.181

−0.104

0.109

−0.015

Osteocalcin

−0.197

−0.053

−0.171

0.061

u-Dpd

−0.244

0.040

0.076

0.011

*p<0.01

In order to analyze the predicting factors for vertebral fracture risk, we employed a univariate logistic regression analysis. When this regression analysis was performed with the presence of vertebral fractures as a dependent variable, age, BMD at any site, serum level of ALP, urinary Dpd, % LBM and % fat were selected (Table 8). When Rad1/3 BMD was analyzed by excluding patients with rheumatoid arthritis, Rad1/3 BMD was not selected for the prediction of vertebral fractures. In multiple logistic regression analysis, % LBM was not significantly related to the risk of vertebral fractures, when % fat was adjusted, suggesting that the relationship between % LBM and vertebral fractures was due to the influence of % fat. Indeed, in multiple logistic regression analysis, % fat was not an independent risk factor for vertebral fractures when FN BMD was adjusted. These findings suggest that % fat affects vertebral fracture risk partly through BMD.
Table 8

Univariate logistic regression analyses in the prediction of vertebral fractures in postmenopausal GC patients

 

Odds ratio

p

Age (years)

1.664

0.0132**

L2-4BMD (g/cm2)

0.065

0.0363**

FN BMD (g/cm2)

0.498

0.0027*

Rad1/3 BMD (g/cm2)

0.602

0.0130**

Albumin (g/dl)

0.884

0.5198

ALP (IU/I)

1.657

0.0160**

intact PTH (pg/dl)

1.275

0.2342

Osteocalcin (μ/l)

0.707

0.1280

u-Dpd (nmol/mmol Cr)

1.952

0.0029*

% LBM (%)

1.718

0.0105**

% Fat (%)

0.625

0.0222**

% Trunk fat (%)

0.845

0.3910

odds ratio were expressed per standard deviation. *p<0.01, **p<0.05

Discussion

Several studies have indicated that fat mass is related to BMD and fracture risk [1719]. In the present study, % fat was significantly lower and % LBM was significantly higher in postmenopausal GC patients with vertebral fractures than in postmenopausal GC patients without fractures. Moreover, % fat was significant in a univariate logistic regression analysis for the prediction of vertebral fractures. These findings indicate that % fat is an important index for predicting vertebral fractures in postmenopausal GC-treated patients. Since nutrition is generally considered to be related to fat, nutritional state may affect bone fragility in GC-treated patients. We previously reported that lumbar spine BMD as well as serum levels of IGF-I and albumin can be used as predictors of vertebral fracture risk in multiple logistic analysis in postmenopausal Japanese women [24]. In that study, urinary GH level was negatively correlated with fat mass in postmenopausal women and serum levels of both IGF-I and IGFBP-3 were positively correlated. These findings suggest the possibility that % fat might affect the fracture risk partly thorough nutritional state and the GH-IGF-I axis. In our previous study [22], LBM was selected as a positive predictor of the risk of osteoporotic vertebral fractures in postmenopausal women. Therefore, it would appear that higher % LBM is reciprocal to lower % fat rather than being directly related to vertebral fracture risk in postmenopausal GC patients.

Our previous study indicated that FN BMD was highly related to fat mass as well as to LBM in postmenopausal women [22]. Total fat mass is one of the major determinants of bone mass, and it is positively correlated with BMD in postmenopausal women [1719]. The present study shows that FN BMD was highly correlated with % fat in GC-treated postmenopausal women, although bone metabolic indices, such as ALP and urinary Dpd, were not significantly related to % fat. These findings suggest that fat affects vertebral fracture risk partly thorough BMD. In previous studies on GC-treated patients [13], BMD at the femoral neck was the best site for predicting the vertebral fracture risk; BMD at the lumbar spine or at distal radius was not as good a predictive index. Therefore, fat, which is closely related to femoral neck BMD, might easily influence fracture risk in GC-treated patients. Percentage fat was not different between the with-vertebral fracture and without-vertebral fracture groups of premenopausal GC-treated patients. This finding suggests that the state of the sex steroid is important for the prevention of fractures in postmenopausal GC-treated patients. The conversion of androgen to estrogen by the adipose tissues becomes a major source of estrogen after menopause [25]. Fat mass is considered to affect BMD by means of the mechanical loading and promotion of intrinsic estrogen production after menopause [26].

BMD at any site was lower in the group with vertebral fractures than in the group without vertebral fractures in all three patient groups of the present study. Thus, body composition might affect vertebral fracture risk through factors other than BMD. Fat tissues produce adipocytokines, such as leptin and adiponectin, which affect bone [2730]. It is therefore possible that the cytokines, such as leptin and adiponectin, may affect bone fragility, resulting in the fracture risk in GC-treated postmenopausal women being affected.

GC excess during adolescence leads to a major persistent deficit in bone mass and an increase in central body fat [31]. Changes in total body and visceral abdominal fat in Cushing syndrome have been described in adults [32, 33]. Thus, patients receiving GC therapy are characterized by a redistribution of fat to central parts of the body, including visceral and subcutaneous fat. Multiple factors influence bone accrual and BMD [32, 33]. Of these, the present study revealed that % trunk fat was significantly higher in the premenopausal GC-treated patients with vertebral fractures than in those without fractures. This difference was not observed in postmenopausal patients. The maximum dose of GC seemed to be somewhat higher in premenopausal women with vertebral fractures than in those without vertebral fractures; these differences were not observed in postmenopausal GC patients (maximum dose of GC: 53.3±16.3 and 42.9±17.2 mg for groups with and without vertebral fractures in premenopausal patients; 31.3±21.0 and 34.8±17.7 mg for groups with and without vertebral fractures in postmenopausal patients). Thus, a higher dose of GC may cause higher % trunk fat as well as bone fragility in premenopausal women, although the reason why % trunk fat was higher in the fracture group in the premenopausal GC patients but not in the postmenopausal GC patients remains unknown. In the simple regression analysis, % trunk fat was significantly correlated to age, body weight, BMI (positive correlation) and Rad 1/3 BMD (negative correlation) (data not shown). In the multiple logistic regression analysis, the significant relationship between % trunk fat and the vertebral fracture risk disappeared only when Rad1/3 BMD was adjusted. These findings suggest that % trunk fat also affects the risk of vertebral fractures partly through BMD, although it remains unknown why % trunk fat affected the fracture risk through reduced radial BMD but not through femoral and lumbar spine BMD. The increased % trunk fat, reduced radial BMD and increased fracture risk may be the correlated results of higher steroid effects in premenopausal patients receiving GC treatment.

The present study has some limitations. First, the sample size was not large enough to make definite conclusions by multiple logistic regression analysis. Secondly, since the subjects employed in the present study included many patients with autoimmune diseases, the nature of the causal diseases for GC treatment may enhance the increased risk of vertebral fractures as well as be the source of disease-specific influences on body composition and fracture risk. Moreover, it is possible that the relationship between % fat and fracture risk is only a correlate.

In conclusion, the results of the present study revealed that body composition is related to vertebral fracture risk in GC-treated patients. Lower % fat was included as a determinant of vertebral fracture risk in postmenopausal GC-treated patients. On the other hand, the present study also reveals that % trunk fat is related to the vertebral fracture risk in premenopausal women.

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© International Osteoporosis Foundation and National Osteoporosis Foundation 2005