Prevalence and risk factors of osteoporosis detected by dual-energy X-ray absorptiometry among Chinese patients with primary biliary cholangitis

Table 1 Demographic, clinical, laboratory, and bone mineral density data in patients with primary biliary cholangitis

Characteristics	Overall (n = 268)	Men (n = 32)	Women (n = 236)	P value
Age (years) (range)	56.7 ± 10.6 (29-94)	60.0 ± 9.3 (38-79)	56.3 ± 10.7 (29-94)	0.059
Age group (years), n (%)				0.201
29-39	13 (4.9)	1 (3.1)	12 (5.1)
40-49	53 (19.8)	2 (6.3)	51 (21.6)
50-59	93 (34.7)	11 (34.4)	82 (34.7)
60-69	77 (28.7)	12 (37.5)	65 (27.5)
≥ 70	32 (11.9)	6 (18.8)	26 (11.0)
Duration of PBC (years)	3.0 (1.0-6.0)	4.0 (1.6-6.8)	3.0 (1.0-6.0)	0.246
Smoking, n (%)	20 (7.5)	17 (53.1)	3 (1.3)	< 0.001
Postmenopausal, n (%)	174 (73.7)		174 (73.7)
Pruritus, n (%)	45 (16.8)	4 (12.5)	41 (17.4)	0.489
Fatigue, n (%)	91 (34.0)	10 (31.3)	81 (34.3)	0.731
Hepatomegaly, n (%)	9 (3.4)	1 (3.1)	8 (3.4)	1.000
Splenomegaly, n (%)	187 (69.8)	20 (62.5)	167 (70.8)	0.340
Gastroesophageal varices, n (%)	110 (41.0)	14 (43.8)	96 (40.7)	0.740
Ascites, n (%)	103 (38.4)	11 (34.4)	92 (39.0)	0.615
Prior fractures, n (%)	11 (4.1)	0 (0.0)	11 (4.7)	0.371
BMI (kg/m2)	22.6 ± 3.3	22.1 ± 3.0	22.7 ± 3.4	0.367
Comorbidities
Diabetes mellitus, n (%)	46 (17.2)	8 (25.0)	38 (16.1)	0.210
Hypertension, n (%)	58 (21.6)	7 (21.9)	51 (21.6)	0.973
Hashimoto's thyroiditis, n (%)	66 (24.6)	7 (21.9)	59 (25.0)	0.700
Rheumatoid arthritis, n (%)	8 (3.0)	0 (0.0)	8 (3.4)	0.602
Sicca syndrome, n (%)	18 (6.7)	1 (3.1)	17 (7.2)	0.706
Previous medication, n (%)
UDCA use	155 (57.8)	24 (75.0)	131 (55.5)	0.036
Steroid use	32 (11.9)	3 (9.4)	29 (12.3)	0.633
Cirrhosis status, n (%)				0.661
Non-cirrhosis	107 (39.9)	15 (46.9)	92 (39.0)
Compensated	53 (19.8)	5 (15.6)	48 (20.3)
Decompensated	108 (40.3)	12 (37.5)	96 (40.7)
PBC-AIH overlap syndrome, n (%)	42 (15.7)	5 (15.6)	37 (15.7)	0.994
Mayo risk score	5.2 ± 1.4	5.4 ± 1.4	5.1 ± 1.5	0.301
Histological stage, n (%)1				0.630
Ⅰ-Ⅱ	65 (39.9)	6 (46.2)	59 (39.3)
Ⅲ-Ⅳ	98 (60.1)	7 (53.8)	91 (60.7)
Laboratory data
ALT (U/L)	36.2 (22.2-70.0)	42.8 (29.0-74.4)	35.8 (21.3-69.7)	0.236
AST (U/L)	46.4 (29.2-88.7)	39.2 (30.1-62.2)	48.1 (29.0-87.7)	0.642
Bilirubin (mg/dL)	1.1 (0.7-1.9)	0.9 (0.7-1.5)	1.1 (0.7-2.0)	0.708
Albumin (g/L)	37.2 ± 6.6	35.5 ± 6.0	37.4 ± 6.6	0.124
ALP (U/L)	157.2 (101.7-263.1)	166.3 (102.8-315.8)	156.5 (101.2-262.4)	0.747
GGT (U/L)	118.2 (48.0-276.3)	146.3 (52.3-321.2)	117.0 (47.6-276.3)	0.568
PTA (%)	93.0 ± 20.6	92.6 ± 19.9	93.0 ± 20.8	0.922
PLT (× 109/L)	140.2 ± 79.4	140.7 ± 80.1	136.2 ± 74.4	0.761
Calcium (mmol/L)	2.22 ± 0.14	2.17 ± 0.16	2.23 ± 0.14	0.018
Phosphorous (mmol/L)	1.14 ± 0.24	1.09 ± 0.17	1.15 ± 0.25	0.201
25-hydroxyvitamin D (ng/mL)2	14.3 ± 6.9	17.2 ± 6.6	13.6 ± 6.9	0.224
Creatinine (μmol/L)	56.4 (49.5-65.9)	67.1 (60.2-86.6)	55.0 (48.6-63.6)	< 0.001
IgM (g/L)	2.86 (1.60-4.40)	2.55 (1.16-4.14)	2.87 (1.64-4.49)	0.240
IgG (g/L)	15.3 (12.0-19.1)	15.0 (11.9-19.3)	15.6 (12.0-19.1)	0.674
gp210 (+), n (%)	99 (36.9)	10 (31.3)	89 (37.7)	0.477
Sp100 (+), n (%)	38 (14.2)	1 (12.5)	34 (14.4)	0.772
ACA, n (%)	54 (20.1)	2 (6.3)	52 (22.0)	0.037
ANA, n (%)	165 (61.6)	21 (65.6)	144 (61.0)	0.615
Lumbar spine BMD (L1-L4), g/cm2	0.828 ± 0.142	0.893 ± 0.146	0.818 ± 0.139	0.005
T-score	-2.04 ± 1.27	-1.81 ± 1.31	-2.1 ± 1.27	0.267
Z-score	-0.929 ± 1.182	-1.18 ± 1.33	-0.89 ± 1.16	0.198
BMD classification, n (%)				0.536
Osteoporosis	108 (40.3)	10 (31.3)	98 (41.5)
Osteopenia	96 (35.8)	13 (40.6)	83 (35.2)
Normal	64 (23.9)	9 (28.1)	55 (23.3)
Femoral neck BMD, g/cm2	0.654 ± 0.128	0.714 ± 0.139	0.646 ± 0.125	0.005
T-score	-1.80 ± 1.12	-1.59 ± 1.03	-1.83 ± 1.13	0.262
Z-score	-0.73 ± 1.02	-0.63 ± 0.99	-0.74 ± 1.03	0.590
BMD classification, n (%)				0.374
Osteoporosis	78 (29.1)	7 (21.9)	71 (30.1)
Osteopenia	123 (45.9)	14 (43.8)	109 (46.2)
Normal	67 (25.0)	11 (34.4)	56 (23.7)
Total Hip BMD, g/cm2	0.784 ± 0.153	0.855 ± 0.148	0.774 ± 0.152	0.005
T-score	-1.42 ± 1.06	-1.19 ± 0.98	-1.45 ± 1.07	0.198
Z-score	-0.64 ± 0.98	-0.70 ± 0.96	-0.63 ± 1.00	0.714
BMD classification, n (%)				0.601
Osteoporosis	45 (16.8)	5 (15.6)	40 (16.9)
Osteopenia	127 (47.4)	13 (40.6)	114 (48.3)
Normal	96 (35.8)	14 (43.8)	82 (34.7)
Osteoporosis lumbar or neck or hip	122 (45.5)	11 (34.4)	111 (47.0)	0.177

¹Available in 163 patients.

²Available in 46 patients.

Data are presented as mean ± SD or median (interquartile range) or n (%). ACA: Anti-centromere antibody; AIH: Autoimmune hepatitis; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; ANA: Antinuclear antibody; AST: Aspartate aminotransferase; BMD: Bone mineral density; BMI: Body mass index; GGT: γ-glutamyl transpeptidase; IgG: Immunoglobulin G; IgM: Immunoglobulin M; PBC: Primary biliary cholangitis; PLT: Platelet count; PTA: Prothrombin activity; UDCA: Ursodeoxycholic acid.

Table 2 Univariate analysis of risk factors for osteoporosis in overall and women patients with primary biliary cholangitis

Variables	Overall patients (n = 268)		P value	Women patients (n = 236)		P value
	Osteoporosis (n = 122)	No osteoporosis (n = 146)		Osteoporosis (n = 111)	No osteoporosis (n = 125)
Women, n (%)	111 (91.0)	125 (85.6)	0.177	111 (100)	125 (100)
Age (year)	60.5 ± 10.5	53.6 ± 9.7	< 0.001	60.4 ± 10.7	52.6 ± 9.4	< 0.001
Duration of PBC (year)	3.0 (1.0-7.0)	2.3 (1.0-5.0)	0.125	3.0 (1.0-7.0)	2.0 (1.0-5.0)	0.217
Smoking, n (%)	9 (7.4)	11 (7.5)	0.961	2 (1.8)	1 (1.6)	0.602
Postmenopausal, n (%)	98 (88.3)	76 (60.8)	< 0.001	98 (88.3)	76 (60.8)	< 0.001
Pruritus, n (%)	22 (18.0)	23 (15.8)	0.619	21 (18.9)	20 (16.0)	0.555
Fatigue, n (%)	50 (41.0)	41 (28.1)	0.026	48 (43.2)	33 (26.4)	0.007
Hepatomegaly, n (%)	2 (1.6)	7 (4.8)	0.188	2 (1.8)	6 (4.8)	0.204
Splenomegaly, n (%)	103 (84.4)	84 (57.5)	< 0.001	96 (86.5)	71 (56.8)	< 0.001
Gastroesophageal varices, n (%)	72 (59.0)	38 (26.0)	< 0.001	66 (59.5)	30 (24.0)	< 0.001
Ascites, n (%)	67 (54.9)	36 (24.7)	< 0.001	61 (55.0)	31 (24.8)	< 0.001
Prior fractures, n (%)	8 (5.0)	3 (2.1)	0.064	8 (7.2)	3 (2.4)	0.080
BMI (kg/m2)	21.6 ± 3.2	23.4 ± 3.3	< 0.001	21.8 ± 3.1	23.4 ± 3.4	< 0.001
Comorbidities
Diabetes mellitus, n (%)	23 (18.9)	23 (15.8)	0.503	20 (18.0)	18 (14.4)	0.450
Hypertension, n (%)	28 (23.0)	30 (20.5)	0.634	26 (23.4)	25 (20.0)	0.524
Hashimoto's thyroiditis, n (%)	27 (22.1)	39 (26.7)	0.386	26 (23.4)	33 (26.4)	0.598
Rheumatoid arthritis, n (%)	4 (3.3)	4 (2.7)	0.796	4 (3.6)	4 (3.2)	0.864
Sicca syndrome, n (%)	8 (6.6)	10 (6.8)	0.924	8 (7.2)	9 (7.2)	0.998
Previous medication
UDCA use, n (%)	78 (63.9)	77 (52.7)	0.065	69 (62.2)	62 (49.6)	0.053
Steroid use, n (%)	23 (18.9)	9 (6.2)	0.001	21 (18.9)	8 (6.4)	0.003
PBC-AIH overlap syndrome, n (%)	17 (13.9)	25 (17.1)	0.475	17 (15.3)	20 (16.0)	0.885
Mayo risk score	5.7 ± 1.5	4.7 ± 1.3	< 0.001	5.7 ± 1.4	4.6 ± 1.2	< 0.001
Histological stage, n (%)1			< 0.001			< 0.001
Ⅰ-Ⅱ	10 (17.2)	55 (52.4)		9 (16.1)	50 (53.2)
Ⅲ-Ⅳ	48 (82.8)	50 (47.6)		47 (83.9)	44 (46.8)
ALT (U/L)	32.0 (20.8-54.8)	43.7 (23.7-84.4)	0.007	31.2 (20.5-31.2)	46.3 (29.1-84.4)	0.013
AST (U/L)	44.0 (29.1-83.7)	49.5 (29.2-91.5)	0.782	46.3 (29.1-84.4)	50.9 (28.7-91.5)	0.899
Bilirubin (mg/dL)	1.2 (0.8-2.40	0.9 (0.7-1.7)	0.002	1.2 (0.8-2.5)	0.9 (0.7-1.6)	0.001
Albumin (g/L)	35.5 ± 6.9	38.7 ± 5.9	< 0.001	35.7 ± 6.9	39.0 ± 5.9	< 0.001
ALP (U/L)	164.2 (110.8-266.3)	149.3 (94.4-261.5)	0.180	164.3 (112.3-265.0)	144.5 (93.6-257.4)	0.175
GGT (U/L)	107.7 (47.9-237.1)	143.1 (47.7-307.3)	0.320	108.5 (45.4-242.5)	129.1 (48.6-303.3)	0.432
PTA (%)	87.9 ± 20.2	97.2 ± 20.1	< 0.001	87.6 ± 20.2	97.8 ± 20.1	< 0.001
PLT (× 109/L)	119.3 ± 71.4	157.7 ± 81.7	< 0.001	116.4 ± 67.4	162.4 ± 84.5	< 0.001
Calcium (mmol/L)	2.20 ± 0.15	2.24 ± 0.13	0.065	2.21 ± 0.14	2.24 ± 0.13	0.100
Phosphorous (mmol/L)	1.15 ± 0.30	1.14 ± 0.17	0.703	1.15 ± 0.31	1.15 ± 0.17	0.869
25-hydroxyvitamin D (ng/mL)2	14.0 ± 7.8	14.5 ± 6.2	0.823	14.1 ± 8.0	13.4 ± 5.8	0.748
Creatinine (μmol/L)	58.4 (47.2-67.5)	56.2 (50.6-65.4)	0.724	55.9 (46.9-67.5)	54.9 (49.9-60.7)	0.710
IgM (g/L)	2.80 (1.53-4.39)	2.87 (1.64-4.63)	0.497	2.87 (1.61-4.49)	2.93 (1.65-4.49)	0.776
IgG (g/L)	15.7 (12.0-19.5)	15.2 (11.9-18.9)	0.453	15.7 (12.3-19.6)	15.3 (11.8-18.6)	0.420
gp210 (+), n (%)	48 (39.3)	51 (34.9)	0.456	45 (40.5)	44 (35.2)	0.398
Sp100 (+), n (%)	19 (15.6)	19 (13.0)	0.550	18 (16.2)	16 (12.8)	0.456
ACA, n (%)	30 (24.6)	24 (16.4)	0.098	29 (26.1)	23 (18.4)	0.153
ANA, n (%)	74 (60.7)	91 (62.3)	0.779	69 (62.2)	75 (60.0)	0.734

¹Available in 163 patients.

²Available in 46 patients.

Data are presented as mean ± SD or median (interquartile range) or n (%). ACA: Anti-centromere antibody; AIH: Autoimmune hepatitis; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; ANA: Antinuclear antibody; AST: Aspartate aminotransferase; BMI: Body mass index; GGT: γ-glutamyl transpeptidase; IgG: Immunoglobulin G; IgM: Immunoglobulin M; PBC: Primary biliary cholangitis; PLT: Platelet count; PTA: Prothrombin activity; UDCA: Ursodeoxycholic acid.

Table 3 Multivariate analysis of risk factors for osteoporosis in overall and women patients with primary biliary cholangitis

Variables	Overall patients (n = 268)		Overall patients underwent liver biopsy (n = 163)		Women patients (n = 236)		Women patients underwent liver biopsy (n = 150)
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Age, per 10 years	1.80 (1.33-2.44)	< 0.001	1.95 (1.30-2.92)	0.001	1.63 (1.04-2.57)	0.035	2.02 (1.27-3.20)	0.003
Fatigue		NS		NS		NS		NS
Splenomegaly		NS		NS	2.62 (1.18-5.80)	0.018		NS
Gastroesophageal varices	2.11 (1.14-3.92)	0.018		NS		NS		NS
Ascites		NS		NS		NS		NS
BMI	0.85 (0.77-0.93)	< 0.001	0.87 (0.77-0.98)	0.023	0.83 (0.75-0.92)	< 0.001	0.85 (0.74-0.97)	0.014
Previous steroid use	4.19 (1.66-10.56)	0.002		NS	4.01 (1.42-11.31)	0.009	3.99 (1.24-12.87)	0.020
Mayo risk score	1.36 (1.08-1.71)	0.009		NS	1.61 (1.22-2.14)	0.001	1.64 (1.12-2.41)	0.011
ALT		NS		NS		NS		NS
Bilirubin		NS	1.20 (1.01-1.42)	0.044		NS		NS
Albumin		NS		NS		NS		NS
PTA		NS		NS		NS		NS
PLT		NS		NS		NS		NS
Postmenopausal					2.92 (1.02-8.38)	0.046		NS
Histological stage Ⅲ or Ⅳ			3.74 (1.60-8.77)	0.002			3.02 (1.13-8.06)	0.027

ALT: Alanine aminotransferase; BMI: Body mass index; CI: Confidence interval; NS: Not significant; OR: Odds ratio; PLT: Platelet count; PTA: Prothrombin activity.