J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 7, Number 10, October 2015, pages 762-769

The Effects of Bazedoxifene on Bone, Glucose, and Lipid Metabolism in Postmenopausal Women With Type 2 Diabetes: An Exploratory Pilot Study

Figure 1. Median percent changes in bone metabolism after 12 weeks of bazedoxifene treatment. Median values (first quartile, third quartile) are -18.6% (-30.9%, 12.9%) for u-NTX, -10.2% (-44.1%, 20.7%) for u-CTX, -20.6% (-27.8%, -5.8%) for TRACP, -10.1% (-17.7%, 8.6%) for OC, and -16.3% (-23.4%, -2.2%) for ucOC. u-NTX: urinary type I collagen cross-linked N-telopeptide; u-CTX: urinary type I collagen cross-linked C-telopeptide; TRACP: tartrate-resistant acid phosphatase 5b; OC: osteocalcin; ucOC: undercarboxylated osteocalcin.

**Table 1.** Patients’ Baseline Characteristics
	Baseline (n = 20)
Data are reported as means ± standard deviation or medians (min - max). BMI: body mass index; YAM: young adult mean; FRAX^® tool: Fracture Risk Assessment Tool; ARBs: angiotensin II receptor blocker.
Age (years)	67.9 ± 5.5
Menopause age (years)	50.2 ± 5.1
Diabetes duration (years)	4.5 (1 - 24)
Height (cm)	153.5 ± 4.4
BMI (kg/m²)	22.5 ± 2.8
HbA1c (%)	6.3 (5.4 - 7.4)
Serum creatinine (mg/dL)	0.61 (0.39 - 0.82)
Microangiopathy
Neuropathy (%)	29 (5/17)
Retinopathy (%)	0 (0/17)
Nephropathy (%)
Stage 1	82 (14/17)
Stage 2	18 (3/17)
Macroangiopathy
Coronary artery disease (%)	5.9 (1/17)
Cerebrovascular disease (%)	24 (4/17)
Peripheral artery disease (%)	0 (0/17)
Smoking (%)
Former smoker	20 (5/20)
Current smoker	0 (0/20)
Alcohol (%)	0 (0/20)
Lumbar
Bone mineral density (g/cm²)	0.9 ± 0.2
T-score	-1.3 ± 1.6
YAM (%)	86.4 ± 17.0
Femoral neck
Bone mineral density (g/cm²)	0.6 ± 0.1
T-score	-1.6 ± 0.8
YAM (%)	78.2 ± 10.9
FRAX^® tool
Major osteoporotic (years)	8.3 (5.2 - 24)
Hip fracture (years)	1.3 (0.4 - 7.6)
History of the vertebral fracture	0 (0/20)
History of the non-vertebral fracture	0 (0/20)
Family history of the femoral neck fracture	0 (0/20)
Medications
Anti-diabetes
Diet only (%)	15 (3/20)
Sulfonylureas (%)	20 (4/20)
Glinides (%)	10 (2/20)
Biguanides (%)	25 (5/20)
DPP-IV inhibitors (%)	45 (9/20)
GLP-1 analogues (%)	10 (2/20)
α-glucosidase inhibitors (%)	5 (1/20)
Insulin (%)	5 (1/20)
Anti-dyslipidemia
Stains (%)	35 (7/20)
Ezetimibe (%)	15 (3/20)
Anti-hypertension
ARBs (%)	30 (6/20)

Table 1. Patients’ Baseline Characteristics

Baseline (n = 20)

Data are reported as means ± standard deviation or medians (min - max). BMI: body mass index; YAM: young adult mean; FRAX^® tool: Fracture Risk Assessment Tool; ARBs: angiotensin II receptor blocker.

Age (years)

67.9 ± 5.5

Menopause age (years)

50.2 ± 5.1

Diabetes duration (years)

4.5 (1 - 24)

Height (cm)

153.5 ± 4.4

BMI (kg/m²)

22.5 ± 2.8

HbA1c (%)

6.3 (5.4 - 7.4)

Serum creatinine (mg/dL)

0.61 (0.39 - 0.82)

Microangiopathy

Neuropathy (%)

29 (5/17)

Retinopathy (%)

0 (0/17)

Nephropathy (%)

Stage 1

82 (14/17)

Stage 2

18 (3/17)

Macroangiopathy

Coronary artery disease (%)

5.9 (1/17)

Cerebrovascular disease (%)

24 (4/17)

Peripheral artery disease (%)

0 (0/17)

Smoking (%)

Former smoker

20 (5/20)

Current smoker

0 (0/20)

Alcohol (%)

0 (0/20)

Lumbar

Bone mineral density (g/cm²)

0.9 ± 0.2

T-score

-1.3 ± 1.6

YAM (%)

86.4 ± 17.0

Femoral neck

Bone mineral density (g/cm²)

0.6 ± 0.1

T-score

-1.6 ± 0.8

YAM (%)

78.2 ± 10.9

FRAX^® tool

Major osteoporotic (years)

8.3 (5.2 - 24)

Hip fracture (years)

1.3 (0.4 - 7.6)

History of the vertebral fracture

0 (0/20)

History of the non-vertebral fracture

0 (0/20)

Family history of the femoral neck fracture

0 (0/20)

Medications

Anti-diabetes

Diet only (%)

15 (3/20)

Sulfonylureas (%)

20 (4/20)

Glinides (%)

10 (2/20)

Biguanides (%)

25 (5/20)

DPP-IV inhibitors (%)

45 (9/20)

GLP-1 analogues (%)

10 (2/20)

α-glucosidase inhibitors (%)

5 (1/20)

Insulin (%)

5 (1/20)

Anti-dyslipidemia

Stains (%)

35 (7/20)

Ezetimibe (%)

15 (3/20)

Anti-hypertension

ARBs (%)

30 (6/20)

**Table 2.** Values of All Clinical Parameters From 0 to 12 Weeks
	0 weeks	4 weeks	12 weeks	P value vs. 4 weeks	P value vs. 12 weeks
Data are reported as medians (min - max). *Patients with insulin therapy (n = 1) were excluded from analysis of HOMA-IR and HOMA-β. UACR: urinary albumin-to-creatinine ratio; NS: no significance.
uNTX (nmol BCE/mmol CRE)	36.9 (16.4 - 126)	28.3 (15.2 - 66.9)	29.7 (20.5 - 74.4)	0.008	NS
uCTX (μg/mmol CRE)	232 (57 - 666)	180 (57-390)	181 (70-414)	0.011	NS
TRACP-5b (mU/dL)	325 (155 - 606)	257 (149 - 472)	259 (141 - 388)	< 0.001	< 0.001
Osteocalcin (ng/mL)	7.7 (4.6 - 13)	7.8 (5.3 - 12)	7.1 (5.3 - 10)	NS	NS
Undercarboxylated osteocalcin (ng/mL)	3.6 (0.9 - 12)	3.7 (1.6 - 10)	3.3 (1.6 - 6.9)	0.002	0.04
Homocysteine (mmol/mL)	6.1 (4.5 - 11.7)	6.2 (4.6 - 13.2)	6.4 (4.3 - 12.4)	NS	NS
Serum pentosidine (μg/mL)	0.042 (0.022 - 0.065)	0.043 (0.031 - 0.069)	0.045 (0.038 - 0.076)	NS	NS
Fasting plasma glucose (mg/dL)	112 (75 - 174)	100 (88 - 158)	105 (78 - 161)	NS	NS
HbA1c (%)	6.3 (5.4 - 7.4)	6.4 (5.5 - 7.3)	6.2 (5.5 - 7.0)	NS	NS
IRI (μU/mL)	5.31 (2.21 - 10.7)	5.33 (2.24 - 11.6)	5.54 (2.28 - 12.8)	NS	NS
sCPR (ng/mL)	1.42 (0.33 - 2.73)	1.4 (0.88 - 3.09)	1.47 (0.14 - 2.86)	NS	NS
HOMA-IR**	1.4 (0.5 - 3.2)	1.3 (0.5 - 2.8)	1.5 (0.9 - 3.4)	0.02	NS
HOMA-β**	45.5 (10.3 - 155)	41.7 (8.49 - 139)	45.4 (8.83 - 107)	NS	NS
HMW adiponectin (μg/mL)	3.46 (1.32 - 10.9)	-	3.37 (1.42 - 12.8)	-	0.024
LDL cholesterol (mg/dL)	124 (53.0 - 154)	107 (58.0 - 151)	108 (50.0 - 168)	0.003	0.037
HDL cholesterol (mg/dL)	76.5 (37.0 - 1 06)	72 (45.0 - 108)	71 (43.0 - 108)	NS	0.027
Non-HDL cholesterol (mg/dL)	130 (64.0 - 167)	117 (70.0 - 157)	115 (58.0 - 170)	0.001	0.01
Triglyceride (mg/dL)	86.5 (44.0 - 258)	108 (42.0 - 187)	110 (39.0 - 193)	NS	NS
baPWV (cm/s)
Rt	1,884 (1,243 - 2,545)	-	1,808 (1,201 - 2,972)	-	NS
Lt	1,867 (1,241 - 2,687)	-	1,836 (1,201 - 3,032)	-	NS
hs-CRP (ng/mL)	431 (86 - 4,520)	563 (148 - 7,120)	468 (109 - 4,990)	NS	NS
Ferritin (ng/mL)	96 (7.1 - 256)	-	90.8 (5.1 - 299)	-	NS
AST (IU/L)	21 (13 - 43)	21 (11 - 42)	20 (12 - 63)	NS	NS
ALT (IU/L)	19 (9 - 48)	17 (7 - 55)	19 (7 - 64)	NS	NS
γ-GTP(IU/L)	19 (12 - 45)	18 (11 - 47)	19 (13 - 47)	NS	NS
Serum Cr (mg/dL)	0.61 (0.39 - 0.82)	0.61 (0.43 - 0.81)	0.61 (0.39 - 0.81)	NS	NS
UACR (mg/g CRE)	13.5 (3.7 - 42.8)	-	10.1 (2.1 - 80.4)	-	NS
Cystatin C (mg/L)	0.59 (0.41 - 0.84)	-	0.55 (0.33 - 0.87)	-	0.009
Weight (kg)	54.5 (42.5 - 70)	54.6 (42.2 - 69)	55 (42.3 - 70)	NS	NS

Table 2. Values of All Clinical Parameters From 0 to 12 Weeks

0 weeks

4 weeks

12 weeks

P value vs. 4 weeks

P value vs. 12 weeks

*Data are reported as medians (min - max). **Patients with insulin therapy (n = 1) were excluded from analysis of HOMA-IR and HOMA-β. UACR: urinary albumin-to-creatinine ratio; NS: no significance.

uNTX (nmol BCE/mmol CRE)

36.9 (16.4 - 126)

28.3 (15.2 - 66.9)

29.7 (20.5 - 74.4)

0.008

uCTX (μg/mmol CRE)

232 (57 - 666)

180 (57-390)

181 (70-414)

0.011

TRACP-5b (mU/dL)

325 (155 - 606)

257 (149 - 472)

259 (141 - 388)

< 0.001

Osteocalcin (ng/mL)

7.7 (4.6 - 13)

7.8 (5.3 - 12)

7.1 (5.3 - 10)

Undercarboxylated osteocalcin (ng/mL)

3.6 (0.9 - 12)

3.7 (1.6 - 10)

3.3 (1.6 - 6.9)

0.002

0.04

Homocysteine (mmol/mL)

6.1 (4.5 - 11.7)

6.2 (4.6 - 13.2)

6.4 (4.3 - 12.4)

Serum pentosidine (μg/mL)

0.042 (0.022 - 0.065)

0.043 (0.031 - 0.069)

0.045 (0.038 - 0.076)

Fasting plasma glucose (mg/dL)

112 (75 - 174)

100 (88 - 158)

105 (78 - 161)

HbA1c (%)

6.3 (5.4 - 7.4)

6.4 (5.5 - 7.3)

6.2 (5.5 - 7.0)

IRI (μU/mL)

5.31 (2.21 - 10.7)

5.33 (2.24 - 11.6)

5.54 (2.28 - 12.8)

sCPR (ng/mL)

1.42 (0.33 - 2.73)

1.4 (0.88 - 3.09)

1.47 (0.14 - 2.86)

HOMA-IR**

1.4 (0.5 - 3.2)

1.3 (0.5 - 2.8)

1.5 (0.9 - 3.4)

0.02

HOMA-β**

45.5 (10.3 - 155)

41.7 (8.49 - 139)

45.4 (8.83 - 107)

HMW adiponectin (μg/mL)

3.46 (1.32 - 10.9)

3.37 (1.42 - 12.8)

0.024

LDL cholesterol (mg/dL)

124 (53.0 - 154)

107 (58.0 - 151)

108 (50.0 - 168)

0.003

0.037

HDL cholesterol (mg/dL)

76.5 (37.0 - 1 06)

72 (45.0 - 108)

71 (43.0 - 108)

0.027

Non-HDL cholesterol (mg/dL)

130 (64.0 - 167)

117 (70.0 - 157)

115 (58.0 - 170)

0.001

0.01

Triglyceride (mg/dL)

86.5 (44.0 - 258)

108 (42.0 - 187)

110 (39.0 - 193)

baPWV (cm/s)

1,884 (1,243 - 2,545)

1,808 (1,201 - 2,972)

1,867 (1,241 - 2,687)

1,836 (1,201 - 3,032)

hs-CRP (ng/mL)

431 (86 - 4,520)

563 (148 - 7,120)

468 (109 - 4,990)

Ferritin (ng/mL)

96 (7.1 - 256)

90.8 (5.1 - 299)

AST (IU/L)

21 (13 - 43)

21 (11 - 42)

20 (12 - 63)

ALT (IU/L)

19 (9 - 48)

17 (7 - 55)

19 (7 - 64)

γ-GTP(IU/L)

19 (12 - 45)

18 (11 - 47)

19 (13 - 47)

Serum Cr (mg/dL)

0.61 (0.39 - 0.82)

0.61 (0.43 - 0.81)

0.61 (0.39 - 0.81)

UACR (mg/g CRE)

13.5 (3.7 - 42.8)

10.1 (2.1 - 80.4)

Cystatin C (mg/L)

0.59 (0.41 - 0.84)

0.55 (0.33 - 0.87)

0.009

Weight (kg)

54.5 (42.5 - 70)

54.6 (42.2 - 69)

55 (42.3 - 70)