Associations of Sex Hormone-binding Globulin with Bone Mineral Density Among US Adults, NHANES 2013–2016

Figures & data

Table 1 Weighted Characteristics of Study Sample Based on Age

	Age <30 Young (n=2137)	Age 30–50 Mid-Age (n=3033)	Age >50 Elderly (n=1264)	p-value
Gender (n)
Male	1094	1459	622
Female	1043	1574	642
Education level (n)
Less than 9th grade	52	247	121
9–11th grade	189	369	159
High school graduate/GED or equivalent	374	628	304
Some college or AA degree	617	910	366
College graduate or above	394	879	314
Body mass index (kg/m^2)	27.17±7.17	29.60±6.92	29.65±6.67
Fasting glucose (mmol/L)	5.30±0.97	5.91±2.02*	6.45±2.39*,**	<0.01
DBP (mmHg)	65.09±11.25	72.82±10.97*	73.77±11.65*,**	<0.01
SBP (mmHg)	113.64±10.83	119.20±14.39*,**	126.72±17.95*,**	<0.01
Total BMD (g/cm^2)	1.11±0.11	1.12±0.11*	1.08±1.12*,**	<0.01
Thoracic spine BMD (g/cm^2)	0.80±0.10	0.83±0.11*	0.80±0.14**	<0.01
Lumbar spine BMD (g/cm^2)	1.04±0.14	1.03±0.15	0.99±0.16**	<0.01
Pelvis BMD (g/cm^2)	1.24±0.17	1.26±0.16*	1.19±0.17*,**	<0.01
Right leg BMD (g/cm^2)	1.18±0.14	1.17±0.13	1.14±0.14*,**	<0.01
Right arm BMD (g/cm^2)	0.79±0.98	0.80±0.10	0.77±0.11*,**	<0.01
Left leg BMD (g/cm^2)	1.17±0.14	1.17±0.13	1.13±0.14*,**	<0.01
Left arm BMD (g/cm^2)	0.77±0.09	0.78±0.10*	0.75±0.11*,**	<0.01
Serum index
Albumin (g/dL)	4.45±0.33	4.31±0.32*	4.27±0.31*,**	<0.01
ALk (IU/L)	65.23±19.66	65.07±22.28	72.45±25.69*,**	<0.01
ASA (IU/L)	25.07±23.36	25.70±21.70	26.83±15.94
ALA (IU/L)	25.03±21.00	27.05±20.74*	27.41±21.83*,**
Bicarbonate (mmol/L)	24.51±2.09	24.60±2.14	25.11±2.22*,**	<0.01
Total calcium (mg/dL)	9.48±0.33	9.32±0.36*	9.40±0.34*,**	<0.01
Cholesterol (mg/dL)	173.05±34.13	196.53±40.61*	203.93±43.81*,**	<0.01
Globulin (g/dL)	2.81±0.39	2.86±0.42*	2.84±0.45	<0.01
Potassium (mmol/L)	3.94±0.30	3.94±0.30	3.98±0.36*	<0.01
Sodium (mmol/L)	139.21±1.98	139.03±2.04*	139.37±2.36**	<0.01
Phosphorus (mg/dL)	3.90±0.57	3.71±0.56*	3.79±0.58*,**	<0.01
Total bilirubin (mg/dL)	0.62±0.33	0.59±0.29*	0.59±0.27*,**	<0.01
Total protein (g/L)	41.61±32.51	41.73±32.06	39.44±31.83
Uric acid (umol/L)	317.40±79.67	313.33±82.92	321.22±80.38
Testosterone (nmol/L)	8.26±8.81	6.74±7.95*	7.07±8.10*	<0.01
Estradiol (nmol/L)	0.19±0.28	0.21±0.27	0.08±0.13*,**	<0.01
SHBG (nmol/L)	53.50±48.63	54.78±38.38	54.44±32.71

Notes: Mean ±SD for continuous variables; p-value was calculated by one-way ANOVA, *p<0.01 vs age <30 young; **p<0.01 vs age 30–50 mid-age.

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; ALK, alkaline phosphatase; ASA, aspartate aminotransferase; ALA, alanine aminotransferase; BMD, bone mineral density.

Figure 1 Research flow chart.

Table 2 Correlation Between BMD in Different Parts and Fasting Glucose/Sex Hormones

Variables	Fasting Blood Glucose		Testosterone		Estradiol		SHBG
	r-value	p-value	r-value	p-value	r-value	p-value	r-value	p-value
Thoracic spine BMD (g/cm^2)	0.105	<0.001	0.119	<0.001	0.16	0.208	−0.117	<0.001
Lumbar spine BMD (g/cm^2)	0.018	0.339	0.009	0.485	0.115	<0.001	0.049	<0.001
Pelvis BMD (g/cm^2)	0.030	0.108	−0.149	0.373	0.099	<0.001	0.012	0.361
Total BMD (g/cm^2)	0.033	0.080	0.223	<0.001	−0.020	0.107	−0.126	<0.001

Notes: Pearson correlation was calculated to assess the strength of relationship between fasting blood glucose, sex hormones and BMD.

Table 3 Associations Between Sex Steroid Hormone (nmol/L) and Lumbar BMD

Variables	Unadjusted			Adjusted
	β	OR (95%CI)	p-value	β	OR (95%CI)	p-value
Fasting glucose	0.02	1.02 (0.98–1.07)	0.32	0.04	1.05 (1.00–1.10)	0.051
Testosterone	0.012	1.01 (1.00–1.02)	<0.01	0.02	1.02 (1.01–1.03)	<0.01
Estradiol	0.96	2.61 (1.82–3.75)	0.013	0.76	2.13 (1.47–3.09)	<0.01
SHBG	0.003	1.00 (1.00–1.01)	<0.01	0.003	1.00 (1.00–1.01)	<0.01

Notes: Unadjusted: no covariates were adjusted; adjusted: age, BMI, ALB, ALK, ASP, calcium, cholesterol, potassium, sodium, total protein, uric acid. Effects are presented in both an unadjusted and an adjusted analysis with effect estimates and p-value. For this analysis 6434 participants were included.

Table 4 Associations Between Sex Steroid Hormone (nmol/L) and Pelvis BMD

Variables	Unadjusted			Adjusted
	β	OR (95%CI)	p-value	β	OR (95%CI)	p-value
Fasting glucose	0.01	1.01 (0.97–1.06)	0.662	0.01	1.00 (0.96–1.05)	0.84
Testosterone	0.007	1.01 (1.00–1.02)	0.116	0.014	1.01 (1.00–1.03)	<0.01
Estradiol	0.50	1.66 (1.18–2.33)	<0.01	0.42	1.52 (1.07–2.18)	<0.01
SHBG	−0.007	0.99 (0.99–1.00)	<0.01	0.10	0.10 (0.99–1.00)	<0.01

Notes: Unadjusted: no covariates were adjusted; adjusted: age, BMI, ALB, ALK, ASP, calcium, cholesterol, potassium, sodium, total protein, uric acid.

Table 5 Associations Between Sex Steroid Hormone (nmol/L) and Total BMD

Variables	Unadjusted			Adjusted
	β	OR (95%CI)	p-value	β	OR (95%CI)	p-value
Fasting glucose	0.01	1.01 (0.97–1.06)	0.637	−0.001	1.00 (0.95–1.05)	0.96
Testosterone	0.05	1.05 (1.04–1.06)	0.116	0.06	1.06 (1.05–1.07)	<0.01
Estradiol	0.44	1.54 (1.12–2.13)	<0.01	0.39	1.48 (1.05–2.07)	0.026
SHBG	−0.002	0.998 (0.996–1.00)	0.02	−0.001	1.00 (1.00–1.002)	0.56

Notes: Unadjusted: no covariates were adjusted; adjusted: age, BMI, ALB, ALK, ASP, calcium, cholesterol, potassium, sodium, total protein, uric acid.

Table 6 Compared Sex Steroid Hormone (nmol/L) with Fasting Glucose to BMD

	Group 1 (n=100)	Group 2 (n=46)	Group 3 (n=169)	Group 4 (n=43)
Lumbar spine BMD (g/cm^2)	0.891±0.164	0.952±0.133	1.048±0.153*,**	1.045±0.150*,**
Pelvis BMD (g/cm^2)	1.189±0.160	1.150±0.162	1.251±0.175*,**	1.250±0.153**
Total BMD (g/cm^2)	1.050±0.114	1.043±0.113	1.149±0.104*,**	1.151±0.092*,**

Notes: *p<0.05 vs group 1; **p<0.05 vs group 2.

Figure 2 Group 1: FBG ≤6.0 and low sex steroid hormone level; group 2: FBG >6.0 and low sex steroid hormone level; group 3: FBG ≤6.0 and high sex steroid hormone level; group 4: FBG >6.0 and high sex steroid hormone level. The data are presented as the means ±SD. Statistical analysis was performed by two-way analysis of variance with all pairwise multiple comparison procedures done by Tukey's method, *p<0.001 vs group 1; **p<0.001 vs group 2.

Table 7 Multivariate Regression Analysis of SHBG on BMD

Variables	Sex	Model 1 OR (95%CI) p-value	Model 2 OR, (95%CI), p-value	Model 3 OR (95%CI) p-value
Thoracic spine BMD (g/cm^2)	Male	0.834 (0.819–0.848) <0.001	0.598 (0.561–0.635) <0.001	0.271 (0.073–0.469) 0.007
	Female	0.82 (0.795–0.808) <0.0001	0.675 (0.656–0.695) <0.001	0.676 (0.651–0.700) <0.001
Lumbar spine BMD (g/cm^2)	Male	1.014 (0.995–1.032) <0.001	0.949 (0.899–0.999) <0.001	0.572 (0.292–0.852) <0.001
	Female	1.022 (1.014–1.031) <0.001	1.028 (1.002–1.055) <0.001	1.044 (1.011–1.077) <0.001
Pelvis BMD (g/cm^2)	Male	1.311 (1.290–1.332) <0.001	1.127 (1.072–1.181) <0.001	0.681 (0.381–0.982) <0.0001
	Female	1.230 (1.221–1.239) <0.001	1.209 (1.182–1.235) <0.001	1.1092 (1.164– 1.220) <0.0001
Total BMD (g/cm^2)	Male	1.141 (1.128–1.155) <0.001	1.054 (1.017–1.09) <0.001	0.722 (0.520–0.925) <0.001
	Female	1.076 (1.067–1.086) <0.001	1.01 (0.979–1.049) <0.001	1.017 (0.979–1.055) <0.001

Notes: Model 1 is adjusted for no variables; model 2 is adjusted for age, BMI, PIR, fasting blood glucose; model 3 is adjusted for calcium, cholesterol, total protein, uric acid, testosterone and estradiol.

Table 8 Compared Sex Steroid Hormone (nmol/L) with Sex to BMD

	Male (n=3175)	Female (n=3259)	p-value
Age	37.39±12.40	37.95±12.13	0.087
Body mass index (kg/m^2)	28.26±6.25	29.32±7.72*	<0.01
Fasting glucose (mmol/L)	5.95±1.92	5.71±1.86	0.414
Total BMD (g/cm^2)	1.14±0.11	1.08±0.10*	<0.01
Thoracic spine BMD (g/cm^2)	0.84±0.12	0.79±0.11	0.067
Lumbar spine BMD (g/cm^2)	1.03±0.16	1.03±0.14*	0.01
Pelvis BMD (g/cm^2)	1.27±0.17	1.21±0.15*	<0.01
Right leg BMD (g/cm^2)	1.24±0.13	1.10±0.11*	<0.01
Right arm BMD (g/cm^2)	0.85±0.08	0.72±0.07*	<0.01
Left leg BMD (g/cm^2)	1.23±0.13	1.09±0.11*	<0.01
Left arm BMD (g/cm^2)	0.83±0.08	0.70±0.07*	<0.01
Testosterone (nmol/L)	8.26±8.81	6.74±7.95*	<0.01
Estradiol (nmol/L)	0.19±0.28	0.21±0.27*	<0.01
SHBG (nmol/L)	53.50±48.63	54.78±38.38*	<0.01

Notes: Data are presented as the means ±SEM. One-way ANOVA followed by a Holm–Sidak test for post-hoc analysis using GraphPad Prism 7. A value of p<0.05 was considered to indicate a statistically significant difference. *p vs male.