Osteoporosis in cirrhotics before and after liver transplantation: relation with malnutrition and inflammatory status

Figures & data

Table 1. Patient characteristics at baseline.

Baseline measurements	Patients with DXA at pre-LT evaluation (N = 102)	Patients with both DXA and blood samples at pre-LT evaluation (N = 75)	Patients with DXA both pre- and post-LT (N = 47)	Patients with both DXA and blood samples at pre-LT evaluation and DXA post-LT (N = 34)
Age (y)	53 (10)	53 (51–55)	49 (46–52)	49 (45–52)
Gender (F)	68%	69%	64%	62%
Comorbid illness	71%	72%	66%	65%
Diabetes mellitus	30%	32%	19%	21%
Etiology of cirrhosis
Alcohol (or mixed)	33%	35%	30%	29%
Cholestatic (PSC or PBC)	22%	21%	32%	32%
Viral	24%	22%	23%	24%
Other	33%	35%	30%	30%
Ascites
Previous ascites	60%	59%	53%	50%
Current ascites	37%	34%	30%	21%
Portal hypertension
Clinical hepatic  encephalopathy	25%	24%	29%	29%
Esophageal varices	75%	74%	73%	77%
Previous variceal bleed	30%	32%	32%	35%
Hepatocellular carcinoma	19%	25%	13%	15%
Severity of liver cirrhosis
Child-Pugh class A/B/C	15% / 47% / 38%	17% / 47% /36%	15% / 43% / 43%	18%/44%/38%
Child-Pugh score, median (IQR)	9 (7–11)	9 (7–10)	9 (8–11)	9 (8–10)
MELD-score, median (IQR)	15 (11–18)	15 (11–18)	15 (15–19)	15 (11–18)
Nutritional status
Malnutrition	28%	27%	26%	24%
Low TSF	20%	20%	15%	15%
Low MAMC	12%	9%	13%	9%
Significant weight loss	17%	14%	14%	13%
Bone measurements
BMD left hip (g/cm^2),  mean (95% CI)	0.98 (0.95–1.02)	0.97 (0.93–1.01)	0.96 (0.91–1.00)	0.94 (0,88–1.00)
Z-score left hip, mean  (95% CI)	−0.22 (−0.46–0.03)	−0.32 (−0.63–(−0.02))	−0.50 (−0.87–(−0.14))	−0.61 (−1.07–(−0.14))
Osteoporosis left hip	7%	9%	6%	9%
Osteopenia left hip	33%	35%	36%	41%

MELD: Model for End stage Liver Disease; TSH: thyroid stimulating hormone; T3: free Triiodthyronine; T4: free Thyroxine; DHEA: dehydroepiandrosterone; TSF: triceps skin fold thickness; MAMC: mid arm muscular circumference; malnutrition defined as BMI < 20 and/or low TSF and/or low MAMC and/or significant weight loss (weight loss of 5–10% or more during the last 3–6 months); CI: confidence interval.

Table 2. Step-wise logistic regression analysis for osteopenia/osteoporosis at baseline.

	Osteopenia/osteoporosis left hip-crude analysis
	Crude analysis^a
	Odds ratio (95% CI)	p-value
Patient characteristics
Gender (if male)	0.96 (0.41–2.27)	.93
Age (per year)	1.00 (0.96–1.04)	.93
Smoking (current)	0.91 (0.36–2.27)	.83
Smoked (current or previous)	0.67 (0.30–1.52)	.34
Alcohol or mixed etiology	0.61 (0.26–1.45)	.26
Cholestatic etiology	2.14 (0.82–5.59)	.12
Child-score	1.07 (0.90–1.28)	.43
MELD-score	1.03 (0.96–1.10)	.47
Child-class C vs. A	1.38 (0.74–2.57)	.31
Child-class B vs. A	1.07 (0.31–3.66)	.92
Bilirubin (per µmol/L)	1.00 (0.99–1.01)	.82
Nutritional status
Malnutrition	3.70 (1.47–9.31)	.006
Significant weight loss	2.41 (0.77–7.50)	.13
TSF (per mm)	0.92 (0.86–0.99)	.01
MAMC (per cm)	0.91 (0.83–1.01)	.09
BMI (per kg/m^2)	0.85 (0.77–0.94)	.002
Inflammation status
TNF-α (per ng/L)	1.02 (0.94–1.10)	.70
IL-6 (per ng/L)	1.00 (0.99–1.01)	.94
CRP (per mg/L)	1.01 (0.99–1.02)	.49
Hormonal status
DHEA (per µmol/L)	1.56 (0.77–3.18)	.22
TSH (per mIE/L)	0.90 (0.66–1.23)	.50
Free T3 (per pmol/L)	0.73 (0.48–1.12)	.15
Free T4 (per pmol/L)	0.88 (0.73–1.06)	.17
Free testosterone (per nmol/L)	1.00 (0.96–1.04)	.97
Estradiol (per fmol/L)	1.00 (0.99–1.01	.97
Cortisol (per nmol/L)	1.00 (0.99–1.01)	.21
Growth hormone (per μg/L)	1.00 (0.98–1.02)	.75
Transplantation related factors
Steroid use pre-LT	1.00 (0.33–3.07)	1.00
Bisphosphonate use pre- LT	0.49 (0.05–4.86)	.54
Steroid dose pre-LT (per mg)	0.98 (0.92–1.05)	.64
	Osteopenia/osteoporosis left hip – adjusted analysis
	Multivariate analysis adjusted for age, sex, MELD-score and cholestatic etiology
Malnutrition	3.49 (1.35–9.02)	.016
TSF (per mm)	0.90 (0.83–0.97)	.008
BMI (per kg/m^2)	0.85 (0.76–0.95)	.004

CI: confidence interval; DHEA: dehydroepiandrosterone; TSH: thyroid stimulating hormone; T3: free Triiodthyronine; T4: free Thyroxine; TSF: triceps skin fold thickness; MAMC: mid arm muscular circumference; BMI: body mass index; LT: liver transplantation.

Malnutrition: BMI < 20 and/or low TSF (low TSF defined as below the 10th percentile according to standard tables for the Swedish population based on age and gender) and/or low MAMC (low MAMC defined as mid arm muscular circumference below the 10th percentile according to standard tables for the Swedish population based on age and gender) and/or significant weight loss (weight loss of 5–10% or more during the last 3–6 months).

^aIn the crude analysis, when the association between low bone mass (osteopenia or osteoporosis) and hormones DHEA, free testosterone and estradiol was tested, sex was included as a covariate.

Those hormones, inflammatory markers and markers of nutritional status, which were statistically significantly associated with low bone mass (osteopenia or osteoporosis) in the crude analysis were thereafter included in a multivariable logistic regression model with the pre-defined covariables age, sex, and MELD- score. Cholestatic etiology was also included in this model because there was a trend towards higher odds of low bone mass for patients with cholestatic etiology in the crude analysis (p = .12).

Significant results (p < .05) are indicated in bold.

Table 3. Mean difference in change of left hip BMD Z-score (from baseline to one-year post-LT) between patients with vs. those without the specified parameter.

(Student’s T-test)	BMD Z-score change left hip
					95 % CI
	N (yes/no)		p-value	Mean diff.	Lower	Upper
Patient characteristics
Smoking at inclusion	8/37		.44	−0.17	−0.60	0.26
Smoked (current or previous)	21/24		.13	−0.25	−0.57	0.07
Sex	30/17		.37	0.15	−0.18	0.49
Etiology
Alcohol or mixed	14/33		.50	−0.12	−0.48	0.23
Cholestatic	15/32		.01	0.43	0.10	0.75
Nutritional status
Malnutrition	15/32		.91	−0.02	−0.40	0.35
Significant weight loss	6/38		.87	−0.04	−0.54	0.45
Transplantation related factors
Steroid use pre-LT	7/40		.22	0.28	−0.17	0.73
Mycophenolate treatment	7/40		.98	−0.01	−0.47	0.45
Bisphosphonate treatment post-LT	9/38		.13	0.31	−0.09	0.71
At least one rejection episode	21/26		.93	0.01	−0.31	0.34
Morbidity post-LT	25/22		.003	−0.46	−0.76	−0.17

CI: confidence interval; LT: liver transplantation.

Malnutrition: BMI < 20 and/or low TSF (Low TSF defined as below the 10th percentile according to standard tables for the Swedish population based on age and gender) and/or low MAMC (Low MAMC defined as mid arm muscular circumference below the 10th percentile according to standard tables for the Swedish population based on age and sex) and/or significant weight loss (weight loss of 5–10% or more during the last 3–6 months). Significant results (p < .05) are indicated in bold.

Figure 1. Scatter plot between hip BMD Z-score change, and concentrations of TNF-α and cortisol at pre-LT evaluation. LT: liver transplantation; BMD: bone mineral density.