Whole body and regional body composition analysis by dual-energy X-ray absorptiometry in cirrhotic patients

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1 European Journal of Clinical Nutrition (1997) 51, 810±814 ß 1997 Stockton Press. All rights reserved 0954±3007/97 $12.00 Whole body and regional body composition analysis by dual-energy X-ray absorptiometry in cirrhotic patients O Riggio 1, A Andreoli 2, F Diana 1, P Fiore 1, P Meddi 1, R Lionetti 1, F Montagnese 1, M Merli 1, L Capocaccia 1 and A De Lorenzo 2 1 II Gastroenterologia, UniversitaÁ, La Sapienza and 2 Fisiologia Umana, UniversitaÁ di Tor Vergata, Rome, Italy Objectives: To compare whole body and regional (arms, legs and trunk) fat mass, fat-free mineral-free mass, bone mineral content and bone mineral density, measured by DXA, in cirrhotic patients and age, sex and BMI matched healthy volunteers. Design: Cross-sectional study. Setting: Two medical research institutions. Subjects: Twenty-two non ascitic cirrhotic patients and 16 age, sex and BMI matched healthy volunteers. Interventions: The Lunar DPX whole-body X-ray densitometer with Lunar software version 3.6z (Lunar Radiation Corp., Madison WI, USA) was used. Regional analysis was performed on the arms, legs, trunk and head. Results: Compared to controls, cirrhotic patients showed a signi cant reduction in percentage body fat. When differentiated by gender, however, the reduction in percentage body fat was evident in female cirrhotics only, particularly in the trunk. In male cirrhotic patients fat-free mineral-free mass was reduced in absolute terms in the whole body and the limbs. For both genders and in each body segment bone mineral content and density were reduced in cirrhotics compared to controls. In cirrhotic patients bone mineral density was signi cantly correlated to both fat-free, mineral-free mass (r ˆ 0.85; P < 0.001) and to the Physical Activity Index (r ˆ 0.52; P < 0.01). Conclusions: Two different patterns of soft tissue loss may be found in cirrhotic patients: in women lean tissue is maintained while fat stores are reduced, as in early starvation; in men lean tissue is reduced, as seen under conditions of stress. Moreover, factors in uencing lean body mass, such as nutritional depletion and physical inactivity, may contribute to the reduction of bone density frequently observed in cirrhotic patients. Sponsorship: This work has been funded by the University of Rome, `La Sapienza' research grant MURST 60%, Descriptors: body composition; dual-energy X-ray absorptiometry; cirrhosis Introduction The measurement of body composition in cirrhotic patients is of particular interest, not only because it can provide additional and more precise information on their nutritional status, but also because the estimation of metabolically active body compartments by means of body composition analysis is essential in standardizing physiological processes, such as energy expenditure and protein turnover. A comparison of these processes between cirrhotics and healthy individuals may help explain the mechanism by which malnutrition arises in these patients. Although several methods have been applied (Madden & Morgan, 1994; Muller et al, 1992; McCullough et al, 1991; Crawford et al, 1994; Olroyd et al, 1993; Prijatmoko et al, 1993), an analysis of body composition in cirrhotic patients is not easy to perform. Simple bed-side methods, skinfold anthropometry for example, while useful for epidemiological purposes (Italian Multicentre Cooperative Project on nutrition in liver cirrhosis, 1994; Merli et al, 1996), are not always accurate (Frost & Corish, 1989). Bioelectrical impedance analysis may not provide valid data on body composition in patients whose state of Correspondence: Dr O Riggio, Via Costantino MAES 68, Roma, Italy. Received 30 December 1996; revised 8 July 1997; accepted 22 July 1997 hydratation is variable (Katch et al, 1986; Jebb & Elia, 1991; De Lorenzo et al, 1991), as is the case with cirrhotic patients (McCullough et al, 1991; Olroyd et al, 1993; Prijatmoko et al, 1993; Guglielmi et al, 1991). The estimation of body composition from Total Body Potassium (TBK) or Total Body Water (TBW) is based on assumptions made regarding healthy individuals and has never been validated in cirrhotic patients in whom TBK may be reduced (Podolsky et al, 1973) and fractional hydratation of body lean and cell mass may be increased (McCullough et al, 1991; Olroyd et al, 1993; Prijatmoko et al, 1993). Finally, the application of in vivo neutral activation analysis (IVNAA) can only be performed in a few specialized centers and thus in a limited number of patients. Dual X-ray absorptiometry is a safe, convenient and non invasive technique for assessing body composition (Mazess et al, 1990). By applying this method Fat Mass (FM), Bone Mineral Content (BMC), namely mass in grams of the inorganic calci ed content of bone, Bone Mineral Density (BMD), namely bone mass per unit of projected bone area in g=cm 2 ) and Fat-Free Mineral- Free Mass (FFMFM) can be estimated, and whole body and regional analysis (arms, legs and trunk) may be performed. This study aimed to determine the above three body compartments in non ascitic cirrhotic patients and age, gender and body size-matched controls.

2 Table 1 Etiology and functional severity of liver injury in the 22 cirrhotic patients 811 Etiology Patients HCV 10 Alcoholic 4 Cryptogenetic 2 HCV alcoholic 2 HBV HDV 2 HBV alcoholic 1 PBC 1 Child±PUGH A 9 B 12 C 1 Bilirubin (mg/dl) Prothrombin activity (%) Albumin (g/dl) HCV ˆ Hepatitis C virus; HBV ˆ Hepatitis B virus; HDV ˆ Hepatitis Delta virus; PBC ˆ Primary Biliary Cirrhosis. Table 2 Comparison between cirrhotic patients and matched healthy volunteers Cirrhotics Controls Sex (M/F) 12/10 7/9 Age NS Weight (kg) NS Height (cm) NS BMI (kg/m 2 ) NS Mean SD. Patients and methods Twenty-two cirrhotic patients hospitalised for diagnostic and=or therapeutic reasons were included in the study. Patient's characteristics are reported in Table 1. Aetiology of liver disease was based on histological, clinical and laboratory variables. The severity of cirrhosis was assessed using the Child-Pugh grading system, performed in each patient on entry. Ten of these patients had clinical and ultrasonographical evidence of uid retention at entry. Fluid retention was treated with diuretics or paracenthesis and body composition measurements were made when ascites (at ultrasonography) or oedema was no longer detectable. Sixteen healthy volunteers of similar age and Body Mass Index were used as controls. The comparison Figure 1 Correlation between whole body mass by DXA and body weight by gravimetry. between cirrhotics and matched controls is reported in Table 2. DXA measurements were made on subjects in the postabsorptive state immediately after emptying the bladder and with no uid intake in the previous 4 hrs. The Lunar DPX whole-body X-ray densitometer with Lunar software version 3.6z (Lunar Radiation Corp., Madison WI, USA) was used. This instrument used a rectilinear scanner, running at medium speed, to detect density differences through the subject, lying undressed on a scan table. Regional analysis was performed on the arms, legs, trunk and head. This analysis provides mass in grams of bone mineral content, fat, lean (fat-free, mineral-free mass) and the sum of the body tissues for segments and whole body. The determination of whole body mass by DXA and body weight by gravimetry were compared (Figure 1). Each patient lled in a questionnaire regarding their usual daily routine. Questions were asked about how many hours are spent sleeping, awake but in repose or in physical activity (housework, personal care, outdoor pursuits, etc.) (Wilson et al, 1986). An index (in percent) was calculated by simply dividing the number of hours devoted to physical activity by 24. Data from cirrhotics and controls were compared using the Student t-test. All results are espressed as mean SD Table 3 Regional analysis of body composition in cirrhotics and controls (MeanSD) (kg) (g=cm 2 ) (kg) (kg) (kg) ( % ) Cirrhotics Arms Controls t-test ns ns ns ns ns ns Cirrhotics Trunk Controls t-test P < P < P < 0.05 ns ns P < Cirrhotics Legs Controls t-test ns ns ns ns ns ns Cirrhotics Total body Controls t-test P < 0.05 P < 0.01 ns ns ns P < 0.05 BMC ˆ Bone Mineral Content; BMD ˆ Bone Mineral Density; FM ˆ Fat Mass; FF-MFM ˆ Fat Free Mineral-Free Mass.

3 812 5), BMC and BMD were signi cantly reduced in both genders and in each body segment compared with respective controls, while percent body fat was signi cantly reduced in female cirrhotics only, particularly in the trunk. In male cirrhotic patients fat-free, mineral-free mass was lower in absolute terms but not in percentage in the whole body or in the limbs (Table 4). In the cirrhotic group the BMD was signi cantly correlated to both body weight (r ˆ 0.65; P < 0.001) and fat-free, mineral-free mass (r ˆ 0.85; P < 0.001), but not to body fat (r ˆ 0.19; ns) (Figure 2). BMD was also correlated to the physical activity index (r ˆ 0.52; P < 0.01). The mean physical activity index of cirrhotic patients was 18 10%. Figure 2 Correlation between whole body BMD and Fat-Free Mineral- Free Mass, Fat Mass and Body Weight in cirrhotic patients. Results Regional and whole body composition analysis in the entire group of cirrhotics and controls is reported in Table 3. A signi cant reduction in whole body bone mineral content, bone mineral density and percent fat was observed in cirrhotics. By dividing the subjects by sex (Tables 4 and Discussion DXA has been introduced as a precise, safe and relatively inexpensive tool to measure body composition in humans. DXA is associated with a low radiation exposure (Lang et al, 1991) and provides bone mineral as well as fat and lean tissue mass, and thus body composition may be estimated according to the three-component model (Lukasky, 1993). DXA has been validated in animal studies where carcass analysis is possible (Svendsen et al, 1993) and in humans by comparing other methods for estimating body composition, such as under-water weighing (Johansson et al, 1993), skinfold thickness, bioelectrical impedance and TBW (Pritchard et al, 1993), TBK and TBN (Aloia et al, 1995). Both the precision and the agreement of DXA with other methods are considered excellent for bone mineral content, and very good for fat mass. On the other hand, DXA tends to underestimate lean mass, especially at highest values (Aloia et al, 1995). In cirrhotic patients DXA has been compared to TBK, BIA and skinfold anthropometry (Bramley et al, 1993) and to a multicompartmental model based on IVNAA and TBW measurements (Prijatmoko et al, 1993). Again a good agreement for fat mass estimation was found for the different methods. The main advantage of DXA is that regional measurements may be made (for each arm, leg, the head and trunk), which are particularly useful in bone mass estimation. In this study, DXA was applied to a group of cirrhotic patients without overt uid retention. This does not exclude slight over-hydration in our patients. However it has been recently shown that slight changes in hydration have little in uence on the estimation of soft tissue composition by DXA (Pietrobelli et al, 1996). The comparison with age Table 4 Regional analysis of body composition in male cirrhotics and controls (Mean s.d.) (kg) (g=cm 2 ) (kg) (kg) (kg) ( % ) Cirrhotics Arms Controls t-test P < P < NS P < NS NS Cirrhotics Trunk Controls t-test P < P < NS NS NS NS Cirrhotics Legs Controls t-test P < P < NS P < P < 0.05 NS Cirrhotics Total body Controls t-test P < P < NS P < 0.01 NS NS BMC ˆ Bone Mineral Content; BMD ˆ Bone Mineral Density; FM ˆ Fat Mass; FF MFM ˆ Fat-Free Mineral-Free Mass.

4 Table 5 Regional analysis of body composition in female cirrhotics and controls (Mean s.d.) (kg) (g=cm (kg) (kg) (kg) ( % ) 813 Cirrhotics Arms Controls t-test NS P < 0.05 NS NS NS NS Cirrhotics Trunk Controls t-test P < 0.01 P < P < 0.05 NS NS P < Cirrhotics Legs Controls t-test P < 0.05 P < NS NS NS NS Cirrhotics Total body Controls t-test P < 0.01 P < 0.01 NS NS NS P < 0.05 BMC ˆ Bone Mineral Content; BMD ˆ Bone Mineral Density; FM ˆ Fat Mass; FF-MFM ˆ Fat Free Mineral-Free Mass. and BMI-matched healthy controls shows that in cirrhotic patients soft tissue is characterised by a reduced percent of fat mass. This agreees with what has already been reported using other methodologies, such as skinfold anthropometry (Madden & Morgan, 1994), TBK (Crawford et al, 1994) and TBW (McCoullogh et al, 1991). However, if a distinction is made between genders, reduced percent fat mass was only evident in females. Gender differences in body tissue loss have already been reported in epidemiological studies on the prevalence of malnutrition in cirrhotic patients (Italian Multicentre Cooperative Project on nutrition in liver cirrhosis 1994; Caregaro et al, 1996). In such studies adipose tissue was more frequently depleted in females than in males with cirrhosis, while lean tissue was more often affected in males. Also, in the present study, fat-free mineral-free mass was signi cantly lower, in absolute terms, in male cirrhotics only. Thus, according to the present and previous observations, two different patterns of tissue loss may be found in cirrhotic patients: in women lean tissue is maintained while fat stores are reduced, as in early starvation; in men lean tissue is reduced and body fat is normal, as seen under conditions of stress. These two patterns of tissue loss have also been observed in cirrhotics by Crawford et al, in 1994, who unfortunately did not provide gender differentiated data. The reason for a gender difference in tissue loss in cirrhotic patients could be merely related to the abundance of fat stores in female, which are progressively used to cope with the metabolic needs until muscle mass remains the exclusive energy store. Conclusions Previous observations on reduced bone mineral content and density in cirrhotic patients (Bonkovsky et al, 1990) are con rmed in our study. Bone loss in patients with cirrhosis of various etiology and not only in those affected by alcoholic or cholestatic liver diseases has emerged as a clinical problem, because bone alterations are not corrected but are even accentuated after liver transplantation (Meys et al, 1994). The mechanism underlying bone loss in cirrhotic patients is complex and multifactorial. One basic assumption, however, is that skeletal mass and density are both in uenced by mechanical loading, namely gravitational forces and muscular activity (Slemenda, 1995). 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