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CLINICAL FEATURES
Vitamin D and Nutritional Status are Related to Bone Fractures in Alcoholics
Emilio González-Reimers1,*, Julio Alvisa-Negrín1, Francisco Santolaria-Fernández1, M. Candelaria Martín-González 1,
Iván Hernández-Betancor 1, Camino M. Fernández-Rodríguez1, J. Viña-Rodríguez1and Antonieta González-Díaz2
1
Servicio de Medicina Interna, Hospital Universitario, Universidad de La Laguna, Ofra s/n, Tenerife, Canary Islands, Spain and
2
Servicio de Medicina
Nuclear, Hospital Universitario, Universidad de La Laguna, Tenerife, Canary Islands, Spain
*Corresponding author: Tel.: +34-922-678600; Fax: +34-922-319379; E-mail: egonrey@ull.es
(Received 4June 2010; in revised form 15 November 2010; accepted 7December 2010)
Abstract —Background: Bone fractures are common in alcoholics. Aims: To analyse which factors (ethanol consumption; liver
function impairment; bone densitometry; hormone changes; nutritional status, and disrupted social links and altered eating habits)
are related to bone fractures in 90 alcoholic men admitted to our hospitalization unit because of organic problems. Methods: Bone
homoeostasis-related hormones were measured in patients and age- and sex-matched controls. Whole-body densitometry was per-
formed by a Hologic QDR-2000 (Waltham, MA, USA) densitometer, recording bone mineral density (BMD) and fat and lean mass;
nutritional status and liver function were assessed. The presence of prevalent fractures was assessed by anamnesis and chest X-ray
film. Results: Forty-nine patients presented at least one fracture. We failed to find differences between patients with and without frac-
tures regarding BMD parameters. Differences regarding fat mass were absent, but lean mass was lower among patients with bone
fracture. The presence of fracture was significantly associated with impaired subjective nutritional evaluation (χ
2
= 5.79, P= 0.016),
lower vitamin D levels (Z= 2.98, P= 0.003) and irregular eating habits (χ
2
= 5.32, P= 0.02). Reduced lean mass and fat mass, and
altered eating habits were more prevalent among patients with only rib fractures (n= 36) than in patients with multiple fractures and/
or fractures affecting other bones (n= 13). These last were more closely related to decompensated liver disease. Serum vitamin D
levels showed a significant relationship with handgrip strength (ρ= 0.26, P= 0.023) and lean mass at different parts of the body, but
not with fat mass. By logistic regression analysis, only vitamin D and subjective nutritional evaluation were significantly, indepen-
dently related with fractures. Conclusion: Prevalent fractures are common among heavy alcoholics. Their presence is related more
closely to nutritional status, lean mass and vitamin D levels than to BMD. Lean mass is more reduced, nutritional status is
more impaired and there is a trend to more altered eating habits among patients with rib fractures, whereas multiple fractures depend
more heavily on advanced liver disease.
INTRODUCTION
Bone loss and fractures are common events in alcoholics,
due in part to both direct and indirect effects of ethanol on
bone remodelling (Diamond et al., 1989;Leslie et al., 2003;
Peris et al., 1995;Spencer et al., 1986;Wezeman et al.,
2000; ) in a dose-dependent fashion (Turner, 2000), but also
to the peculiar style of life of the alcoholic, prone to falls,
traffic accidents and violence. The term ‘Battered alcoholic
syndrome’was coined >30 years ago by Oppenheim (1977)
to define the situation of a chronic alcoholic who presented
with at least three bone fractures, at different sites and in
different healing stages.
Among alcoholics, probably rib fractures constitute the
most frequently observed ones (González-Reimers et al.,
2005), and in many cases, the patients are not aware of them,
partly due to the anaesthetic effect of ethanol, but also
because of inebriation. Although rib fractures have not been
considered as classic osteoporotic fractures, in a large study
including nearly 6000 elderly men, rib fractures were the most
commonly observed ones, and they were related in most cases
to falls from the standing position (Barrett-Connor et al.,
2010). Importantly, hip bone density was an independent risk
factor for rib fracture, and also, rib fracture was an indepen-
dent risk factor for a new hip fracture. Therefore, at least in
elderly men (Barrett-Connor et al., 2010), rib fracture should
be considered as an osteoporotic fracture, in a similar way as
wrist or hip fractures. A similar conclusion was reached by
Ismail et al. (2006), especially among women. However, falls
from standing height being the main cause of rib fracture,
inebriation, muscle atrophy and/or neuropathy, and the
peculiar style of life of the alcoholic patient surely play a role
in the high prevalence of these fractures. For instance, Keso
et al. (1988) found that thoracic fractures were more com-
monly observed among unmarried, divorced or widowed alco-
holics. However, in addition to these factors, it is clear that
heavy prolonged ethanol consumption also constitutes a risk
for classic osteoporotic fractures, such as hip fracture (Felson
et al., 1988). Indeed, ethanol exerts direct effects on bone syn-
thesis and resorption, leading to decreased bone mass. Besides
these direct effects, altered nutrition (Santolaria et al., 2000),
altered liver function (Chappard et al., 1991;Jorge-Hernández
et al., 1988) and ongoing drinking (Alvisa-Negrín et al.,
2009;Peris et al., 1994) also play a role.
The main objective of this study was to analyse which
factors (ethanol consumption; liver function impairment;
bone densitometry; hormone alterations; nutritional status
and environmental factors related with job, social status and
eating habits) are related to bone fracture in a cohort of 90
heavy-alcoholic men admitted to our hospitalization unit
because of organic problems. Since, as commented, subtle
differences, largely depending on the style of life and social
environment of alcoholics, may exist between the mechan-
isms leading to rib fractures and the classical osteoporotic
fractures in these patients, we have compared all the data
mentioned before among patients with only rib fractures and
patients with other types and/or multiple fractures.
PATIENTS AND METHODS
Patients and controls
We included 90 alcoholic patients, aged 50.14 ± 10.99 years
(median = 49; inter-quartile range (IR) = 42–58), all of whom
Alcohol and Alcoholism Vol. 46, No. 2, pp. 148–155, 2011 doi: 10.1093/alcalc/agq098
Advance Access Publication 19 January 2011
© The Author 2011. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved
by guest on December 29, 2015Downloaded from
were heavy drinkers of more than 100 g ethanol/day (212 ±
79 g/day) for prolonged time periods (29.4 ± 9.7 years) until
the day of admission, and 30 age-matched controls, who
were sanitary workers and drinkers of <10 g/day. The total
amount of ethanol consumed by the patients until the
inclusion in the study was 33.88 ± 16.36 kg ethanol/kg body
weight (median = 33; IR = 19–50). In 50 cases, serology for
hepatitis C virus (HCV) and hepatitis B virus (HBV) was
performed, being positive in 10 cases for HCV and in 4 for
HBV (anticore antibodies; surface antigen was negative in
all cases). Patients were also categorized into cirrhotics and
non-cirrhotics according to clinical grounds and ultrasound
findings, and to liver biopsy when clinically indicated. A
total of 40 cirrhotics were included; Child’s classification
(based on the presence and characteristics of ascites and
encephalopathy, and on serum albumin, bilirubin and pro-
thrombin activity) was used to assess severity. According to
this score, 2 patients belong to Child A (less severe), 13 to
Child B (moderately severe) and 25 to Child C (most severe)
groups. Strictly speaking, the Child-Pugh score is only appli-
cable to cirrhotics. However, alcoholic liver disease is an
ongoing process, and decompensated liver cirrhosis is the
last stage of it. It is difficult, sometimes, to differentiate
between compensated cirrhosis (i.e. Child A patients) and
non-cirrhotic alcoholic liver disease on clinical grounds only,
as it happens in this study with two patients who did not
undergo liver biopsy, whereas it is relatively easy to clearly
identify decompensated (Child C) cirrhotics. Therefore, we
have also classified our sample in two groups: decompen-
sated (Child C) patients and compensated (non-cirrhotics +
Child A and Child B) ones.
The presence of fracture was recorded by anamnesis and
examination of clinical records and thoracic X-ray. If a rib
fracture was discovered in the X-ray plain film without
having been reported by the patient, the patient and their
relatives were asked again. Forty-nine patients had suffered
fractures at the inclusion in the study: rib fracture, affecting
one or two adjacent ribs, in 36 cases, three or more rib frac-
tures affecting non-consecutive ribs (more than one fracturing
episode), and/or non-simultaneous fractures in other places,
in 9 further cases, 2 cases of hip fracture, distal radius in one
case and multiple simultaneous fractures (traffic accident) in
one further case. We classified our patients in those with
only rib fractures (n= 36) and those with multiple + osteo-
porotic fractures (n= 13).
Following a previously reported protocol (Santolaria
et al., 2000), we also recorded the following: (a) the
eating habits of the patients, asking them where they
usually eat (if at home or in bars or taverns), how many
times a day they eat and what they eat (sandwiches or
snacks, or normal dishes), classifying them in three cat-
egories: normal: the patient eats three times a day (break-
fast, lunch and dinner), usually at home, with the family;
irregular habits (loss of some meals, substitution of some
dishes by snacks); and poor eating habits (usually in bars
or taverns, in the form of sandwiches or snacks, once or
twice daily); (b) the social environment of the patient ,
also classifying it into three categories (the best one: with
stable family and work; deranged: living alone, widowed,
unmarried or divorced, eventually unemployed; and the
worst one: skid-row patients, i.e. lonely, unemployed and/
or homeless patients, usually heavy drinkers).
Nutritional evaluation
In addition, subjective nutritional evaluation was performed
to all the patients, as follows: we examined the muscle
masses of the upper and lower limbs and of the temporal
muscle, defining two degrees of atrophy (severe, moderate)
and absence of atrophy, and assigned 2, 1 and 0 points to
each category, respectively. We also recorded, by physical
examination, the fat loss on the cheek and abdomen,
Bichat’s fat and subcutaneous fat atrophy, and classified
them in a similar way, and defined a score (SNS), based on
the sum of the assigned points, for which the poorest value
was 10 and 0 the best one was. We further classified our
patients as well nourished (0–2 points), moderately under-
nourished (3–4 points) and severely undernourished (5–10
points), since this classification is related to the prognosis
(Hernández-Plasencia et al., 1991).
We recorded handgrip strength with a dynamometer, body
mass index, triceps skinfold with a Holtain lipocaliper and
brachial perimeter with a tap, and determined serum biliru-
bin, prothrombin activity and serum albumin and other
routine laboratory tests. We also collected blood samples
after overnight fast. Samples were stored at −80°C until the
following hormones and biochemical markers were
determined.
Whole body composition
After informed consent, the 90 patients and 30 controls
underwent assessment of bone mineral density (BMD), as
well as lean mass and fat mass (only 26 controls) at different
body parts, such as arms, ribs, legs, trunk and total body,
with a HOLOGIC QDR-2000 (Waltham, MA, USA). In 85
cases and 28 controls, BMD was assessed at the lumbar
spine and hip, recording BMD and Z- and T-scores (defined
following standard criteria, Cummings et al., 2002) at the
femoral neck, trochanter, Ward’s triangle, intertrochantereal
area, total hip and lumbar spine (L2–L4).
Biochemical parameters
We determined serum osteocalcin (to 79 patients), by immu-
nometric chemiluminiscent assay (recovery = 97–121%; vari-
ation coefficients of assays ranging from 3.5 to 7.1%; DPC,
Los Angeles, CA, USA), as a marker of bone synthesis, and
C-terminal telopeptide of type I collagen (CrossLaps), by
one-step enzyme-linked immunosorbent assay (ELISA), with
a recovery ranging from 94 to 107% and an intra- and inter-
assay variation coefficient ranging 4.7–4.9 and 5.4–8.1%,
respectively (Osteometer Bio Tech A/S, Herlev, Denmark),
as a marker of bone breakdown in non-cirrhotics. This par-
ameter was determined only to 53 patients. We also deter-
mined serum IGF-1 (Chemiluminiscent assay, DPC, Los
Angeles, CA, USA) to 87 patients; 1, 25 dihydroxyvitamin
D3 to 73 patients (radioimmunoassay, Nichols, San Juan
Capistrano, CA, USA), parathyroid hormone (PTH) to 87
patients; serum free testosterone to 49 patients; serum
RANKL, to 50 patients, by ELISA, with a sensitivity of
0.08 pmol/l and a variation coefficient of 5% or less
(intra-assay) and 9% or less (Immundiagnostik, Bensheim,
Germany); and osteoprotegerin to 64, by sandwich ELISA,
with a sensitivity of 0.14 U/l, and intra-assay and inter-assay
Bone Fractures in Alcoholics 149
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variation coefficients <10% (Biovendor, Brno, Czech
Republic).
The study protocol was approved by the local ethical com-
mittee of our Hospital (2009/23) and conforms to the ethical
guidelines of the 1975 Declaration of Helsinki.
Statistics
The Kolmogorov–Smirnov test was used to test for normal
distribution, a condition not fulfilled by PTH, vitamin D,
IGF-1 and serum telopeptide. Therefore, non-parametric
tests, such as Mann–Whitney’sUtest and Kruskall–Wallis,
were used to analyse differences of these parameters between
groups. Student’st-test, variance analysis and Pearson’s cor-
relation analysis were used with the remaining parameters
(related to bone mass), whereas Spearman’s rho (instead of
Pearson’s correlation) was utilized in the case of non-
parametric variables.
To assess which parameters the presence of fracture
depends on, we performed stepwise logistic regression analy-
sis between fracture and several variables, which showed a
relation with fractures in the univariate analysis, or which
could be potentially involved in the pathogenesis of fractures,
as commented in the results section, and also, among those
with fracture, a logistic regression analysis to discern which
factors were associated with rib fractures or with multiple
fractures. All these analyses were performed with the SPSS
program (Chicago, IL, USA).
RESULTS
Differences between patients and controls
Differences in clinical and biochemical parameters between
patients and controls, as well as T-score values for lumbar
spine and hip, and BMD at several parts of the skeleton are
shown in Table 1. Decreased BMD was observed in the
included patients, who also showed lower T-scores than con-
trols. In Table 1, we also show data relative to lean and fat
mass. Clearly, patients showed less lean mass, but a similar
amount of fat (besides at the trunk) than controls.
Differences between patients with fractures
and without fractures
As shown in Table 2, 49 patients presented at least one bone
fracture at the time of inclusion. We failed to find differences
between patients with and without fractures regarding BMD
parameters. On the contrary, there were significant differ-
ences regarding lean mass, especially between patients with
rib fracture and patients with other types of fractures and
non-fractured patients. Although there was also a trend
Table 1. Clinical and biochemical parameters in patients and controls. Results are given as mean ± standard deviation and, in those non-parametric variables,
also median (inter-quartile range). Data relative to lean and fat mass include only 26 controls
Patients (90) Controls (30) T (Z); P-value
Age (years) 50.14 ± 10.49 50.11 ± 10.40 T= 0.03; NS
Serum ASAT (U/l ) 114.0 ± 99.5 –
Serum ALAT (U/l ) 59.4 ± 41.8 –
Serum GGT (U/l) 302.5 ± 455.5 –
Osteocalcin (ng/ml ) 3.13 ± 3.18 7.37 ± 2.69 T= 4.73; P< 0.001
Serum telopeptide (nmol/l) 0.603 ± 0.388 0.53 (0.43–0.65) 0.211 ± 0.095 0.17 (0.14–0.34) Z= 4.9; P< 0.001
Serum vitamin D (pg/ml ) 28.27 ± 14.68 24.00 (17.0–37.5) 85.37 ± 27.10 88.39 (59.18–112.55) Z= 5.2; P< 0.001
Serum IGF-1 (ng/ml) 106.73 ± 97.82 62.6 (32.6–153.0) 192.00 ± 106.13 135.00 (121.38–259.9) Z= 4.21; P< 0.001
Serum PTH (pg/ml ) 64.95 ± 86.12 41.80 (25.90–75.50) 87.95 ± 141.15 40.84 (19.37–65.31) Z= 0.7; NS
Serum free testosterone (ng/dl) 10.06 ± 10.58 7.82 (3.07–13.38) 18.09 ± 3.84 18.41 (14.81–20.44) Z= 3.79; P< 0.001
Serum cortisol (µg/dl) 14.32 ± 5.58 18.19 ± 4.55 T= 2.66; P= 0.009
Serum osteoprotegerin ( pmol/l) 12.86 ± 6.54 6.83 ± 1.79 T= 3.54; P< 0.001
Serum RANKL (pmol/l ) 0.14 ± 0.22 0.06 (0.01–0.17) 0.08 ± 0.07 0.08 (0.02–0.15) Z= 0.03; NS
Subtotal BMD (g/cm
2
) 0.98 ± 0.10 1.08 ± 0.08 T= 4.96; P< 0.001
Pelvis BMD (g/cm
2
) 1.04 ± 0.15 1.18 ± 0.13 T= 4.85; P< 0.001
Right leg BMD (g/cm
2
) 1.22 ± 0.13 1.35 ± 0.12 T= 5.22; P< 0.001
Left leg BMD (g/cm
2
) 1.22 ± 0.13 1.36 ± 0.12 T= 5.38; P< 0.001
Left arm BMD (g/cm
2
) 0.80 ± 0.10 0.85 ± 0.08 T= 2.75; P= 0.007
Right arm BMD (g/cm
2
) 0.81 ± 0.08 0.83 ± 0.07 T= 1.32; NS
Left rib BMD (g/cm
2
) 0.61 ± 0.07 0.70 ± 0.07 T= 6.45; P< 0.001
Right rib BMD (g/cm
2
) 0.60 ± 0.07 0.70 ± 0.06 T= 6.96; P< 0.001
Thoracic spine BMD (g/cm
2
) 0.90 ± 0.13 0.98 ± 0.11 T= 2.94; P= 0.004
Total hip T-score −1.05 ± 1.16 (n= 85) −0.07 ± 1.18 (n= 28) T= 3.48; P< 0.001
Lumbar spine T-score −1.15 ± 1.18 (n= 85) −0.56 ± 0.90 (n= 28) T= 2.12; P= 0.036
Left arm lean (g) 2535 ± 608 3000 ± 448 T= 3.62; P< 0.001
Right arm lean (g) 2781 ± 595 3099 ± 469 T= 2.51; P= 0.013
Trunk lean ( g) 26,301 ± 3655 26,094 ± 3008 T= 0.26; NS
Left leg lean (g) 7191 ± 1596 8187 ± 1135 T= 2.97; P= 0.004
Right leg lean (g) 7467 ± 1563 8467 ± 1024 T= 3.07; P= 0.003
Total lean ( g) 49,951 ± 6984 53,032 ± 5927 T= 1.98: P= 0.05
Left arm fat (g) 1322 ± 749 1429 ± 516 T= 0.69; NS
Right arm fat (g) 1438 ± 916 1536 ± 575 T= 0.52; NS
Trunk fat (g) 8812 ± 5057 11,770 ± 3860 T= 2.76; P= 0.007
Left leg fat (g) 3071 ± 1528 3330 ± 1042 T= 0.81; NS
Right leg fat (g) 3044 ± 1516 3379 ± 1057 T= 1.05; NS
Total fat (g) 18,706 ± 9273 22,366 ± 6364 T= 1.89; NS
150 González-Reimers et al.
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regarding fat parameters, differences were not statistically
significant ( probably due to the higher values of standard
deviations).
When patients with rib and multiple fractures were pooled
together and compared with patients without fracture regard-
ing lean and fat mass, significant differences were observed
only regarding right arm lean mass, lower among those with
fracture (2660 ± 555 g) than among those without fracture
(2925 ± 615 g, t= 2.15; P= 0.034). The presence of fracture
was significantly associated with subjective nutritional evalu-
ation (χ
2
= 5.79, P= 0.016). Indeed, 12 out of 49 individuals
with fracture (24.49 %) were severely undernourished, in
contrast with 3 out of 41 without fracture (7.32%). A non-
significantly higher proportion of patients with multiple frac-
tures (53.85%) were well nourished when compared with
patients with only rib fractures (47.22%).
Among biochemical parameters, only vitamin D (KW =
9.18, P= 0.01; Table 2) was lower among those with frac-
tures, both among those with only rib fractures and among
those with multiple fractures. When all the patients with frac-
ture were grouped and compared with those without fracture,
serum levels of 1, 25 (OH)
2
D3 were significantly lower in
the former (median (IR) = 21 (15–27) pg/ml ) than in the
latter (35 (21–44) pg/ml; Z= 2.98; P= 0.003). Interestingly,
serum vitamin D levels showed a significant relationship
with handgrip strength (ρ= 0.24, P= 0.046), left arm lean
Table 2. Body composition analysis, including bone mineral density (BMD, in g/cm
2
), lean mass and fat mass and biochemical and epidemiological
parameters in patients with and without fractures. Results are given as mean ± standard deviation and, in those non-parametric variables, also median
(inter-quartile range)
Only rib fracture (n= 36) Hip + multiple fracture (n= 13) No fracture (n= 41)
Left arm BMD 0.79 ± 0.10 0.78 ± 0.09 0.81 ± 0.10 F= 0.82; NS
Right arm BMD 0.81 ± 0.08 0.79 ± 0.08 0.82 ± 0.09 F= 0.62; NS
Left ribs BMD 0.60 ± 0.08 0.62 ± 0.08 0.60 ± 0.07 F= 0.43; NS
Right ribs BMD 0.60 ± 0.07 0.62 ± 0. 09 0.60; ± 0.07 F= 0.50; NS
Thoracic spine BMD 0.89 ± 0.11 0.88 ± 0.15 0.92 ± 0.15 F= 0.84; NS
Lumbar spine BMD 0.95 ± 0.12 0.93 ± 0.18 0.98 ± 0.18 F= 0.44; NS
Pelvis BMD 1.03 ± 0.13 1.04 ± 0.19 1.05 ± 0.16 F= 0.15; NS
Left leg BMD 1.20 ± 0.12 1.20 ± 0.15 1.24 ± 0.14 F= 1.03; NS
Right leg BMD 1.21 ± 0.12 1.20 ± 0.16 1.23 ± 0.13 F= 0.43; NS
Subtotal BMD 0.98 ± 0.09 0.97 ± 0.12 0.99 ± 0.10 F= 0.29; NS
Osteocalcin (ng/ml ) (31/12/36) 2.38 ± 2.01 1.70
(1.10–2.85)
2.61 ± 1.48 2.40
(1.35–3.80)
3.95 ± 4.14 2.05
(1.00–6.45)
KW = 0.65; NS
Serum telopeptide (nmol/l)
(23/9/21)
0.58 ± 0.27 0.54
(0.44–0.64)
0.75 ± 0.81 0.46
(0.34–0.75)
0.56 ± 0.20 0.54
(0.42–0.67)
KW = 0.37; NS
Serum vitamin D (pg/ml)
(28/12/32)
24.06 ± 10.97 24.0
(15.0–27.0)
24.00 ± 17.45 19.0
(15.0–24.8)
33.69 ± 15.15 35.0
(21.0–44.0)
KW = 9.18; P= 0.01
Serum PTH (pg/ml) (35/13/39) 56.63 ± 48.20 40.6
(25.4–72.4)
125.71 ± 190.67 54.8
(36.6–91.6)
52.17 ± 41.61 39.5
(24.2–67.5)
KW = 2.69; NS
Free testosterone (ng/dl) (15/6/28) 7.40 ± 5.31 6.9
(3.2–12.9)
8.10 ± 6.78 6.90
(2.05–12.93)
11.91 ± 12.95 8.27
(2.17–17.70)
KW = 0.56; NS
Serum cortisol (µg/dl) (33/12/36) 13.34 ± 4.35 14.24 ± 6.23 15.25 ± 6.31 F= 1.00; NS
Osteoprotegerin (pmol/l)
(27/8/29)
13.60 ± 7.47 12.50 ± 5.24 12.27 ± 5.89 F= 0.30; NS
Serum RANKL (pmol/l )
(19/8/23)
0.15 ± 0.25 0.06
(0.01–0.21)
0.17 ± 0.30 0.05
(0.013–0.23)
0.11 ± 0.16 0.04
(0.02–0.11)
KW = 0.07 NS
Serum IGF-1 (ng/ml) (33/13/33) 122.9 ± 103.6 94.3
(35.7–195)
84.8 ± 81.9 32.6
(25.9–148.9)
99.2 ± 97.7 55.4
(41.7–127.0)
KW = 3.13; NS
Age (years) 49.22 ± 8.47 52.31 ± 15.11 50.26 ± 11.63 F= 0.38; NS
Total hip T-score (35/13/37) −1.14 ± 1.14 −1.14 ± 1.26 −0.90 ± 1.11 F= 0.48; NS
L2–L4 T-score (35/13/37) −1.13 ± 0.82 −1.54 ± 1.58 −1.13 ± 1.35 F= 0.65; NS
Left arm lean (g) 2344 ± 539 2745 ± 547 2636 ± 600 F= 3.27; P= 0.04,
1 vs. 2
Right arm lean (g) 2598 ± 529 2830 ± 611 2925 ± 615 F= 3.09; P= 0.051
Trunk lean ( g) 25,094 ± 2742 28,790 ± 3296 26,571 ± 4060 F= 5.62; P= 0.005,
2 vs. 1,3
Left leg lean (g) 6794 ± 1358 7665 ± 1209 7388 ± 1834 F= 2.05; NS
Right leg lean (g) 7130 ± 1381 7778 ± 1292 7664 ± 1758 F= 1.44; NS
Total lean ( g) 47,528 ± 5447 53,576 ± 6259 50,930 ± 7765 F= 4.68: P= 0.012,
1 vs. 2,3
Left arm fat (g) 1101 ± 598 1499 ± 609 1458 ± 867 F= 2.70; NS
Right arm fat (g) 1172 ± 677 1606 ± 684 1618 ± 1105 F= 2.61; NS
Trunk fat (g) 7713 ± 5998 10,614 ± 3595 9206 ± 4386 F= 1.83; NS
Left leg fat (g) 2764 ± 1471 3483 ± 1303 3211 ± 1623 F= 1.38; NS
Right leg fat (g) 2695 ± 1470 3537 ± 1182 3194 ± 1611 F= 1.88; NS
Total fat (g) 16,466 ± 10333 21,725 ± 6653 19,715 ± 8722 F= 2.03; NS
Handgrip strength ( pounds) 142.8 ± 69.3 108.3 ± 60.9 163.7 ± 80.6 F= 2.64; NS
Triceps skinfold (mm) 8.14 ± 5.34 8.69 ± 6.69 8.45 ± 6.07 F= 0.05; NS
Brachial perimeter (cm) 27.46 ± 4.68 26.85 ± 3.65 27.24 ± 4.06 F= 0.10; NS
Daily ethanol consumption ( g) 208 ± 79 213 ± 80 215 ± 81 F= 0.07; NS
Years of consumption 30 ± 8 33 ± 14 27 ± 9 F= 1.73 NS
Body mass index (kg/m
2
) 24.02 ± 3.42 25.99 ± 3.11 25.54 ± 4.03 F= 1.83; NS
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mass (ρ= 0.26, P= 0.024), right arm lean mass (ρ= 0.31, P
= 0.004), trunk lean mass (ρ= 0.26, P= 0.024) and total lean
mass (ρ= 0.28, P= 0.017), but not with fat mass.
Irregular feeding habits were significantly associated with
an increased risk of fractures (χ
2
= 5.32, P= 0.021). Also, a
nearly significant association was found between the type of
fracture and eating habits: normal eating habits were
recorded only in 18.2% of the alcoholics with multiple frac-
tures, in 8.82% of those with only rib fractures, but in
40.62% of patients without fractures (P= 0.057).
A non-significant trend was observed between deranged
social environment and fracture (P= 0.14). Social links were
not disrupted in 69.7% of those without fractures, in 63.6%
with multiple fractures and in 52.94% with only rib fractures.
Relationships between type of fracture, liver function,
alcohol intake and tobacco
Thirteen patients were affected by multiple fractures. Of
these, eight were cirrhotics and five non-cirrhotics, However,
neither the association between cirrhosis and type of fracture
(χ
2
= 1.63, P= 0.2) nor the association between cirrhosis and
any kind of fracture (χ
2
= 0.87, P= 0.3; Table 3) were statisti-
cally significant. There were no relationships between both
the type of fracture and the presence of fracture with any of
the variables included in the Child-Pugh’s score (ascites,
encephalopathy, prothrombin, albumin and bilirubin). We
also failed to find an association between Child’s severity
groups and the presence of fracture (χ
2
= 0.04, P= 0.8) or the
kind of fracture (χ
2
= 0.79, P= 0.3). However, when patients
of the Child C groups were compared with the remaining
patients, the proportion of multiple fractures was
significantly higher (32 vs. 7.7%) among Child C patients,
and that of only rib fractures was slightly higher (43.1 vs.
32%) among compensated patients (χ
2
=5; P= 0.025;
Table 3).
Cirrhotics showed in general lower T-score values at the
lumbar spine (t= 3.15, P= 0.003), but not at the femoral neck,
and also lower BMD values at different parts of the skeleton
(Table 4). Cirrhotics showed lower values of vitamin D (Z=
2.54, P= 0.011) and IGF-1 (Z=3.2, P= 0.001) than non-
cirrhotics, but no differences in lean or fat mass.
Significant differences in total BMD (t= 2.15, P= 0.034),
total hip T-score (t= 2.13, P= 0.036) and lumbar spine
T-score (t= 2.42, P= 0.018) were observed between patients
with decompensated liver disease (Child C patients, who
showed lower values of the aforementioned parameters)
and those without decompensated liver disease. In addi-
tion, decompensated patients showed lower IGF-1 (Z= 3.61,
P< 0.001) and testosterone (Z= 2.19, P= 0.028) and also
nearly significantly lower vitamin D levels (Z= 1.91, P=
0.056) than the remaining patients. No differences were
observed in lean and fat mass, except trunk lean mass, which
was significantly higher (t= 2.42, P= 0.018) in decompen-
sated patients (a result which may be in relation with the
presence of ascites).
Among cirrhotics, those with multiple fractures showed, in
general, a tendency to lower BMD and T-score values,
although the only significant difference was observed regard-
ing lumbar spine T-score values, which were lower among
those with multiple fractures (−2.06 ± 1.50) than those
without fractures (−1.82 ± 0.70) and those with only rib frac-
tures (−1.10 ± 0.80, F= 3.4, P= 0.04). On the contrary, no
differences were observed, among non-cirrhotics, between
patients with only rib fractures, multiple fractures or no
fractures.
In 87 patients, tobacco consumption was recorded. No
association was found between smoking and fracture (71.8%
among smokers, 60.4% among non-smokers).
Logistic regression
By stepwise logistic regression analysis, introducing the par-
ameters of age, cirrhosis, lumbar spine (L2–L4) T-score,
total hip T-score, total BMD, total lean mass, total fat mass,
subjective nutritional evaluation, duration of ethanol con-
sumption and the hormones IGF-1, cortisol and vitamin D
(classified in two groups, below or above the median), only
vitamin D (P= 0.034) and subjective nutritional evaluation
Table 3. Fractures in Child C patients compared with the remaining ones,
and among cirrhotics and non-cirrhotics
Multiple
fractures (%)
Rib
fractures
(%)
No fractures
(%)
Advanced liver disease (Child C
patients)
8 (32) 8 (32) 9 (36)
Non-advanced liver disease (Child A
and B + non-cirrhotic alcoholics)
5 (7.7) 28 (43.1) 32 (49.2)
χ
2
5.00; P= 0.025
Cirrhotics 8 (20) 16 (40) 16 (40)
Non-cirrhotics 5 (10.4) 19 (39.6) 24 (50)
χ
2
1.63; NS
Table 4. Differences in BMD between cirrhotics and non-cirrhotics
Cirrhotics (n= 40) Non-cirrhotics (n= 48)
Left arm BMD (g/cm
2
) 0.78 ± 0.08 0.82 ± 0.09 T= 2.10; P= 0.039
Right arm BMD (g/cm
2
) 0.80 ± 0.08 0.83 ± 0.08 T= 1.85; NS
Left ribs BMD (g/cm
2
) 0.59 ± 0.07 0.62 ± 0.07 T= 2.12; P= 0.037
Right ribs BMD (g/cm
2
) 0.59 ± 0.07 0.62 ± 0.06 T= 2.57; P= 0.012
Thoracic spine BMD (g/cm
2
) 0.87 ± 0.12 0.93 ± 0.14 T= 2.15; P= 0.034
Lumbar spine BMD (g/cm
2
) 0.93 ± 0.14 0.99 ± 0.17 T= 1.82; NS
Pelvis BMD (g/cm
2
) 1.01 ± 0.14 1.07 ± 0.15 T= 2.08; P= 0.04
Left leg BMD (g/cm
2
) 1.21 ± 0.14 1.23 ± 0.12 T= 0.93; NS
Right leg BMD (g/cm
2
) 1.20 ± 0.11 1.24 ± 0.13 T= 1.36; NS
Total BMD (g/cm
2
) 1.06 ± 0.09 1.11 ± 0.10 T= 2.33; P= 0.022
Total hip T-score −1.25 ± 0.96 −0.80 ± 1.14 T= 1.92; NS
Lumbar spine T-score −1.57 ± 1.01 −0.81 ± 1.22 T= 3.15; P= 0.003
152 González-Reimers et al.
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(P= 0.021) showed a significant relation with the presence
or not of fracture in the univariate analysis, although subjec-
tive nutritional evaluation displaced vitamin D in the final
formula (P= 0.019). On the contrary, vitamin D remained
the only parameter related to fracture (P= 0.017), displacing
subjective nutritional evaluation, when variables such as cor-
tisol or IGF-1 (which did not show any relations with frac-
ture in the present study) were removed. Also, vitamin D
remained the only parameter related to fracture (P= 0.019)
even if the variable ‘decompensated liver disease’(Child C
patients) was introduced.
Considering only patients with fractures and comparing
those with rib fractures and those with multiple fractures,
introducing the variables age, cirrhosis, lumbar spine (L2–
L4) T-score, total hip T-score, total BMD, total lean mass,
total fat mass, subjective nutritional evaluation, duration of
ethanol consumption and the hormones IGF-1, cortisol and
vitamin D (classified in two groups, below or above the
median), the variables which entered the final formula were
total lean mass (P= 0.024), total fat mass (P= 0.029) and
liver cirrhosis (P= 0.046), in this order.
However, the variable ‘decompensated liver disease’
(Child C patients) displaces the variable ‘cirrhosis’from the
final formula. Again, total lean mass was the first parameter
selected (P= 0.031), but ‘decompensated liver disease’was
the second (P= 0.023) and total fat mass, the third one (P=
0.035). These three parameters remain selected if we remove
IGF-1 and cortisol.
DISCUSSION
In contrast with some population-based studies, which report
a reduced relative risk for hip fracture associated to mild or
moderate alcohol consumption (Berg et al., 2008;Wosje and
Kalkwarf, 2007), but in accordance with other authors who
studied alcoholic patients (Clark et al., 2003;
González-Calvín et al., 1993;Lindholm et al., 1991;Malik
et al., 2009;Peris et al., 1992), we found marked differences
between alcoholics and controls regarding BMD, and total
hip and lumbar spine T-scores. Osteoporosis (T-score < −
2.5) was found in nine cases at the lumbar spine and in five
cases at the hip. These are findings similar to others pre-
viously reported by our group and by many others, irrespec-
tive of the method used to assess osteoporosis (Alvisa–
Negrín et al., 2009;Crilly et al., 1988;Diamond et al., 1989;
Farley et al., 1985;Feitelberg et al., 1987;
García-Valdecasas-Campelo et al., 2006;González-Calvín
et al., 1993;Jorge-Hernández et al., 1988;Lalor et al., 1986;
Peris et al., 1992;Santolaria et al., 2000, among others). In
our study, decreased bone mass heavily depends on
decreased bone synthesis, estimated on the basis of osteocal-
cin values. Biochemical variables related with bone remodel-
ling, such as PTH and RANKL, were not significantly
different in patients and controls, but serum telopeptide,
which may be influenced by liver collagen metabolism
(Ricard-Blum et al., 1996), was also higher among non-
cirrhotics (0.53 ± 0.27 ng/ml ) when compared with controls
(Z= 4.00; P< 0.001).
More than 50% of the patients analysed showed bone frac-
tures. This is quite a high figure compared with those
reported by other authors, such as Keso et al. (1988),
Wilkinson et al. (1985) or Peris et al. (1995), who found
prevalence figures around 35%, although they focused
mainly in detecting rib fractures or radiologically assessed
vertebral fractures.
Low vitamin D levels and deranged nutritional status were
the main factors associated with fracture. Interestingly,
although, in general, BMD values were lower among those
with fractures, differences were not statistically significant.
This result is in agreement with those reported by Peris et al.
(1995) and Santori et al. (2008) regarding vertebral fractures
assessed by radiological criteria. BMD is the most widely
used technique to define osteoporosis (Cummings et al.,
2002), but it may not accurately estimate the fracture risk,
due to the fact that factors related with bone quality are not
assessed by this technique. Moreover, the accuracy of other
recently introduced parameters seem to be higher than the
classic BMD T-score value < −2.5, at least for prediction of
vertebral fractures (Diacinti et al., 2010). In contrast to
BMD, serum vitamin D (1, 25 (OH)
2
D3) levels were sig-
nificantly lower among those with fractures. Although in
some studies, there were no differences in serum vitamin D
between alcoholic patients with and without fractures
(Wilkinson et al., 1985), a similar result to that reported in
this study was found by other authors, such as Santori et al.
(2008), who reported no differences in BMD in a cohort of
alcoholics with a high prevalence of vertebral and non-
vertebral fractures, but indeed lower vitamin D values in the
former; or Diamond et al. (1989) and Malik et al. (2009),
who found lower 25 OH vitamin D levels in alcoholics than
in controls. It is in this sense worthy of note that low vitamin
D levels have been put in relation with increased risk of
falls, and thus, with bone fractures; in fact, treatment with
vitamin D reduced the risk of falling among older individuals
(Bischoff-Ferrari et al., 2009). In the last decade, it was
shown that a receptor for 1, 25 OH vitamin D3 is present in
human skeletal muscle (Bischoff et al., 2001), activation of
which leads to muscle cell proliferation and differentiation
(Ceglia, 2008), and to an increase in the synthesis of calmo-
dulin (Dittranti et al., 1990), leading to improved muscle
function. Although it was not an aim of our study, it is
important to remark that there was a significant relationship
between handgrip strength and serum vitamin D levels, as
well as between vitamin D and lean mass, fully in accord-
ance with the aforementioned statements, and with the
results of a recently published experimental study in which
we also described a significant relationship between type II
fibre atrophy and serum 1, 25 (OH)
2
vitamin D levels in
rats treated following the Lieber-deCarli model (González-
Reimers et al., 2010).
In addition to impaired nutritional status, statistically sig-
nificant differences were observed regarding several par-
ameters related to lean mass and the presence of fractures.
Also a trend was observed to lower values of handgrip
strength among patients with fracture. Both findings are also
in accordance with the relation observed between fractures
and nutritional status, and in accordance with the current
knowledge about this item (Huang et al., 1996). Nutritional
status was evaluated in our patients with a subjective scale
and it was related with fracture. Also, those with the worst
nutritional status showed the lowest vitamin D levels (χ
2
=
4.25; P= 0.039). Therefore, the presence of fracture in our
population was related with vitamin D, subjective nutritional
Bone Fractures in Alcoholics 153
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evaluation and lean mass, but vitamin D is related to nutri-
tional status.
Some differences did exist between patients with only rib
fractures and patients with other types of fractures. In
general, patients with rib fractures showed worse nutritional
parameters, especially lean mass parameters, than patients
with other types of fractures, although there were no differ-
ences in BMD and in biochemical parameters. Rib fractures
are among the most commonly suffered by alcoholics, so
that they have been considered as markers of alcohol con-
sumption in patients affected or not by chronic liver disease
(Israel et al., 1980;Lindsell et al., 1982). As stated before,
rib fractures are frequently observed in elderly, frail individ-
uals, prone to falls (Barrett-Connor et al., 2010). In this
sense, the alcoholics with rib fractures share some of these
characteristics: they are those with less lean and fat mass,
and also with the more deranged eating habits, also showing
a trend to a more intense social margination. Nutritional
status is in part related to bizarre eating behaviour in alco-
holics (Santolaria et al., 2000). Usually, the heavy drinker
disrupts his social links, become divorced or separated, and
his eating habits evolve to more irregular ones. This may
explain why we found an association between irregular
feeding habits and bone fractures, and also the trend to an
association of irregular eating habits and rib fracture. A
similar finding was also reported by Keso et al. (1988),who
showed that socio-economic status did not influence the
prevalence of fractures, but thoracic fractures were more
commonly observed among unmarried, divorced or widowed
alcoholics.
It may seem counterintuitive that patients with multiple
fractures showed, in general, better nutrition, reduced lean
mass and a trend to more fat mass, and a even a trend to
better social and familial environment, than those with only
rib fractures. However, these findings may be interpreted in
several ways. One explanation may consist in the fact that rib
fractures may appear even after minor trauma, such as falling
from a standing position, something which is very common
in the advanced alcoholic patient, with muscle atrophy and
reduced lean mass, severely impaired nutritional status, and,
perhaps, accompanying polineuropathy and/or cerebellar
atrophy, whereas multiple fractures may occur after major
trauma, fighting and violence among less fragile alcoholics,
with preserved lean and fat mass, and, in general, better
environmental conditions.
However, an association was found between multiple frac-
tures and liver cirrhosis and/or decompensated liver disease.
These patients showed lower values of hormones directly
involved in bone homoeostasis, such as vitamin D, IGF-1
and testosterone, decrease in which may play a role in the
frequency of fractures. A third factor which must be con-
sidered is that the variables trunk and total lean mass, which
were higher among cirrhotics and decompensated patients,
are in fact measuring also water retention and not just
muscle mass. Indeed, ascites is one of the criteria of decom-
pensation of liver disease, and, as expected, it is by far more
frequent among decompensated patients than among com-
pensated ones (χ
2
= 13.7; P< 0.0001).
Thus, our study shows that prevalent fractures are
common among heavy alcoholics, but their presence is
related more closely to impaired nutritional status and
reduced lean mass (especially among alcoholics with only
rib fractures) and low serum vitamin D levels, than to BMD.
Interestingly, a relation was found between vitamin D levels,
handgrip strength and lean mass, in accordance with the
described effects of vitamin D on muscle structure and func-
tion. Multiple fractures depend more heavily on the presence
of decompensated liver disease, with decreased levels of
IGF-1, testosterone and vitamin D. In our study, these
patients showed a trend to a more preserved nutritional status
than those with only rib fractures.
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