Keywords
rotator cuff - obesity - body mass index - diabetes - arterial hypertension - ultrasonography
Introduction
Obesity, which is defined by the World Health Organization (WHO) as abnormal or excessive
accumulation of body fat, is considered a public health problem due to its high prevalence
and associated consequences.[1]
[2]
[3] The incidence of this condition has increased exponentially in recent years, reaching
more than 10% of the world population.[4] In Brazil, between 2006 and 2018, there was an increase of more than 67% in the
number of obese individuals.[5]
Research has shown that the increase in body mass index (BMI) is an important factor
related to chronic metabolic diseases (type-2 diabetes mellitus [DM2], systemic arterial
hypertension (SAH) and dyslipidemia)[6]
[7]
[8] and certain disorders of the musculoskeletal system.[9]
[10]
[11] Excess body weight is associated with an increased risk of developing cardiovascular
diseases and early onset of cardiac morbidity.[1]
[6]
[7]
[8] The variables to assess obesity, such as the BMI and abdominal circumference, are
considered independent and modifiable factors associated with SAH, DM2 and dyslipidemia.[1]
[2]
[12]
In addition to these correlations that have already been scientifically disseminated,
obesity seems to contribute to tendon lesions, such as those to the rotator cuff (RC),
predisposing the tendon to degeneration and rupture.[9]
[10]
[11]
[13] The biological plausibility for such an association may be linked to the release
of proinflammatory adiponines, leading to oxidative stress and a state of chronic
systemic inflammation.[9]
[14] Other metabolic (DM and SAH) and demographic (age and gender) factors are also considered
potentially associated with the causality or worsening of tendinopathies, thus being
the focus of recent studies.[15]
[16] The tendon in diabetic individuals is characterized by increased thickness and volume,
with disorganization of the collagen fibers.[17]
[18] Such abnormalities seem to be the result of decreased peripheral blood flow and
local angiogenesis.[15] In addition, SAH-related damage, such as microvessel injury, may aggravate vascular
deficiencies in the critical RC zone, leading to hypoxia and the production of reactive
oxygen species, culminating in cellular apoptosis and tissue degeneration.[19]
[20]
Despite these findings, there is still a scarcity in the scientific literature regarding
studies that establish a relationship among high BMI (> 30 kg/m2), abdominal circumference, and the time of exposure to obesity with lesions to the
RC tendons in different populations in Brazil. Moreover, scientific controversy on
this topic still exists, since other studies have not reported such an association
(between obesity and RC lesions).[21]
[22] Similarly, the relationship among RC lesions in obese individuals and metabolic
and demographic factors are not yet fully established.
Therefore, we firstly hypothesize that the occurrence and severity of RC injuries
are associated with obesity (assessed by BMI and abdominal circumference) and the
time of exposure to obesity. Secondly, we believe that demographic and metabolic factors
are related to RC injuries, and that the prevalence of metabolic dysfunctions is higher
among individuals with injuries compared to those without injuries. To test these
hypotheses, we conducted a cross-sectional study in obese adult patients.
Methodology
Study design and participants
The target population of the present cross-sectional study was composed of men and
women who were cared for at the endocrinology and obesity outpatient clinic of our
institution between 2018 and 2019.
Patients with BMI > 30 kg/m2 and aged between 18 and 65 years were included. Volunteers who presented direct risk
factors for RC injury, such as previous trauma, smoking, shoulder surgery, glenohumeral
instability, chronic corticosteroid use, infiltrations, rheumatoid arthritis, advanced
glenohumeral arthrosis, calcareous tendrosis, any other diagnosis of calcification,
as well as those who did not agree to sign the Free and Informed Consent Form (FICF)
or who did not complete all stages of the study, were excluded from the study.
The sample size (n) required for the study was calculated using the 95% confidence
interval and a significance level of 5%, considering the highest variance (25%). The
number of patients (one thousand) cared for at our institution in the period of 12
months was relevant, representing the target population. The calculation of the sample
size was made based on the estimated proportions.[23] Therefore, in order for the study to have relevance, 235 individuals should be surveyed.
The original sample consisted of 329 individuals. Of these, 94 (28.6%) were excluded
because they did not complete all stages of the study, and 235 (71.4%) qualified individuals
remained [(Figure 1]).
Fig. 1 Flowchart of the patients in the study.
Ethical approval
The present research was approved by the Ethics in Research Committee under the opinion
number: 3,733,973. All participants were volunteers and signed the FICF, confirming
that they were aware of the procedures to be performed and agreed with the research
objectives.
Bias
Caution was taken to avoid misunderstandings regarding the participants' responses.
The researchers refrained from making any comments that could lead to answers contrary
to the truth conveyed by the patients.
Data collected and evaluations
The study participants were initially interviewed to collect demographic (age and
gender) and metabolic factors (prevalence of SAH, DM, lipid profile and time of exposure
to obesity).
The physical examination involved: the evaluation of anthropometric data pertaining
to weight and height, which was performed with the patients wearing light clothing
and no shoes (based on these data, the individual BMI was calculated); abdominal circumference;
and clinical tests to guide the diagnosis of RC injury (the Jobe, Patte and Gerber
tests), wich were performed according to their descriptions.[24]
[25]
[26] To close the diagnosis of complete or partial RC injury, a musculoskeletal ultrasound
examination was performed bilaterally in all patients, using the protocol established
by Selvaraj et al.[27] Ultrasonography is a reliable method, presenting high accuracy in the diagnosis
of RC lesions.[28]
The physical examinations of the volunteers were performed by a physician with residency
in orthopedics and traumatology, specialized in shoulder/elbow surgery, at the endocrinology
and obesity outpatient clinic of our institution. The imaging examinations were performed
by a physician specialized in musculoskeletal ultrasonography, with a diploma issued
by Associação Médica Brasileira in the field of radiology and diagnostic imaging.
Both were independent evaluators, without employment ties to the institutions involved,
and were unaware of any information related to the research objectives.
Definitions
The BMI was calculated based on weight in kilograms divided by height in square meters.
Obesity was defined as BMI > 30 kg/m2. The analysis of the abdominal circumference was performed with a measurement made
0.5 cm to 1.0 cm above the navel with the subjects breathing naturally. The time of
exposure to obesity was calculated considering the first time the participant reached
a BMI > 30 kg/m2 (evaluated by analyzing the previous history reported by the patients themselves).
Diabetes mellitus was defined as fasting plasma glucose of 7.0 mmol/L or by a previous
diagnosis made by a medical professional. Systemic arterial hypertension was defined
according to the following criteria: systolic blood pressure of 140 mmHg, diastolic
blood pressure of 90 mmHg, and/or self-reported hypertension. The lipid profile was
analyzed based on the levels of total cholesterol, low-density lipoprotein (LDL),
and high-density lipoprotein (HDL) by a complete lipidogram performed up to six months
before the study.
Statistics
The demographic, metabolic and physical characteristics of the sample were calculated
using descriptive statistics, including frequencies, means, and standard deviations
(SDs). In order to compare the demographic, metabolic and physical variables of the
patients with and without RC injury, two groups were created (with RC injury and without
RC lesion) and analyzed using the the Student t-test and the Chi-squared test. A multivariate analysis that identified the demographic,
metabolic and physical variables associated with RC injury was performed through binary
logistic regression with the stepwise variables selection method (step-by-step). Finally,
the receiver operating characteristic (ROC) curve was used in order to identify the
best cut-off point for the age variable regarding the presence of RC injury. The data
were analyzed using the Statistical Package for the Social Sciences (SPSS, IBM Corp.,
Armonk, NY, US) software, version 26. The level of statistical significance was established
at p < 0.05.
Results
The demographic, metabolic, physical characteristics and the profile of RC lesions
in the sample are detailed in [Tables 1] and [2] respectively.
Table 1
|
N
|
Average
|
( ± Standard deviation)
|
|
Demographic factors
|
|
Female gender
|
157
|
|
|
|
Male gender
|
78
|
|
|
|
Age (years)
|
|
40.5
|
11.1
|
|
Metabolic factors
|
|
Low-density lipoprotein (mg/dL)
|
|
101
|
35
|
|
High-density lipoprotein (mg/dL)
|
|
49.4
|
11.9
|
|
Total cholesterol (mg/dL)
|
|
183
|
38
|
|
Systemic arterial hypertension ratio (yes/no)
|
85/150
|
|
|
|
Diabetes mellitus ratio (yes/no)
|
42/193
|
|
|
|
Time of exposure to obesity (years)
|
|
11.7
|
8.1
|
|
Physical factors
|
|
Weight (kg)
|
|
102
|
22
|
|
Height (cm)
|
|
166
|
10
|
|
Body mass index (kg/m2)
|
|
36.8
|
5.7
|
|
Abdominal circumference (cm)
|
|
114
|
15
|
Table 2
|
N
|
%
|
|
Presence of injury
|
|
Yes
|
55
|
23.4%
|
|
No
|
180
|
76.6%
|
|
Injured limb
|
|
Right
|
32
|
58.2
|
|
Left
|
7
|
12.7
|
|
Both
|
16
|
29.1
|
|
Type of injury
|
|
Partial rupture
|
49
|
89.1
|
|
Total rupture
|
6
|
10.9
|
|
Site of general injury
|
|
Supraspinal
|
47
|
85.5
|
|
Infraspinal
|
6
|
10.9
|
|
Subscapularis
|
2
|
3.6
|
Comparison of demographic, metabolic and physical factors in obese individuals with
and without rotator cuff injury
The data showed that, in the subgroup with injury, age (p < 0.001), presence of DM (p = 0.013), SAH (p < 0.001), HDL level (p = 0.026) and time of exposure to obesity (p < 0.001) presented significantly higher results compared to those of the group without
RC lesion ([Table 3]).
Table 3
|
Rotator cuff injury (n = 55)
|
No rotator cuff injury (n = 180)
|
p-value
|
|
N
|
Average
|
( ± Standard deviation)
|
N
|
Average
|
( ± Standard deviation)
|
|
|
Demographic factors
|
|
|
|
|
|
Female gender
|
36
|
|
|
121
|
|
|
|
|
Male gender
|
19
|
|
|
59
|
|
|
|
|
Age (years)
|
|
46
|
11.2
|
|
38.6
|
10.4
|
< 0.001
|
|
Metabolic factors
|
|
|
|
|
|
Low-density lipoprotein (mg/dL)
|
|
100
|
35
|
|
101
|
35
|
0.90
|
|
High-density lipoprotein (mg/dL)
|
|
53.4
|
16
|
|
48.2
|
10
|
0.026
|
|
Total cholesterol (mg/dL)
|
|
186
|
40
|
|
182
|
37
|
0.54
|
|
Systemic arterial hypertension ratio (yes/no)
|
33/55
|
|
|
52/180
|
|
|
< 0.001
|
|
Diabetes mellitus ratio (yes/no)
|
16/55
|
|
|
26/180
|
|
|
0.013
|
|
Time of exposure
to obesity (years)
|
|
15
|
9.1
|
|
10.7
|
7.5
|
< 0.001
|
|
Physical factors
|
|
|
|
|
|
Weight (kg)
|
|
102
|
21
|
|
102
|
22
|
0.94
|
|
Height (cm)
|
|
165
|
10
|
|
167
|
11
|
0.38
|
|
Body mass index (kg/m2)
|
|
37.2
|
5.5
|
|
36.6
|
5.7
|
0.54
|
|
Abdominal circumference (cm)
|
|
114
|
15
|
|
115
|
15
|
0.88
|
On average, the individuals with RC injury were 7.4 years older, and had higher prevalences
of SAH and DM, of 31.3% and 15% respectively, in addition to about 4.3 years more
of exposure to obesity.
Association between rotator cuff injury and obesity
In the evaluation by binary logistic regression ([Table 4]), no association was found regarding RC injury and BMI (p = 0.82), time of exposure to obesity (p = 0.29), or abdominal circumference (p = 0.52) in the sample studied. In addition, there was no significant correlation
regarding BMI (rs = -0.029; p = 0.83), time of exposure to obesity (rs = 0.061; p = 0.66), and the severity of the RC lesion.
Table 4
|
Coefficient
|
Odds ratio
|
95% confidence interval
|
p-value
|
|
Demographic factors
|
|
|
Age (years)
|
0.057
|
1.06
|
1.03–1.09
|
0.0003
|
|
Metabolic factors
|
|
|
Systemic arterial hypertension
|
0.984
|
2.68
|
1.38–5.20
|
0.004
|
Association between demographic and metabolic factors with rotator cuff injury
In the search for other independently-associated (demographic and metabolic) parameters
for RC injury, an association was observed between age (p = 0.0003) and SAH (p =0.004) ([Table 4]), thus demonstrating that the older the age and presence of SAH, the higher the
probability of RC injury. Using the ROC methodology, with a sensitivity of 65.5% and
a specificity of 66.7%, we determined that age ≥ 43 years was a cutt-off point fot
the presence of RC injury ([Figure 2]).
Fig. 2 Receiver operating characteristic (ROC) curve. Identification of the cut-off point
for the age variable for the presence of rotator cuff lesion: ≥ 43 years.
Discussion
The relationship between obesity and musculoskeletal system injuries, such as tendinopathies,
is the focus of scientific studies and controversies.[9]
[10]
[11]
[13]
[21] Recent studies[11] suggest an important association between tendon lesions and other metabolic disorders
(SAH and DM).
Therefore, we firstly analyzed the relationship regarding the presence and severity
of RC injury and obesity and the time of exposure to obesity. Secondly, we evaluated
the relationship and prevalence of demographic and other metabolic factors in obese
individuals with RC injury. In the present cross-sectional epidemiological study,
no associations were found regarding the occurrence and severity of the RC injury
and BMI, abdominal circumference and the time of exposure to obesity. However, individuals
with injury presented a longer time of exposure to obesity and a higher prevalence
of metabolic diseases (SAH and DM) than patients without injury. Finally, SAH and
advanced age were factors related to the presence of RC lesion.
The highest susceptibility to ruptures and tendon degeneration in individuals with
high BMI and abdominal circumference values has a physiological explanation linked
to increased adipokine production (tumor necrosis factor-alpha, leptin, adiponectin,
angiotensinogen, and interleukins 6, 8, 10 and 18), leading to oxidative stress, inflammation,
endothelial dysfunction and cellular apoptosis.[9]
[11]
[14] The first case-control study to establish such a clinical association of the occurrence
and severity of RC lesions and obesity was conducted by Gumina et al.[9] The authors evaluated 381 patients, demonstrating that individuals with a mean BMI
of 30 kg/m2 presented more than twice the number of lesions as non-obese individuals. Moreover,
the higher the BMI measured, the higher the degree of RC lesions evidenced. However,
Titchener et al.,[22] in a study with a large sample (5,000 patients), concluded that only overweight
(25.1 kg/m2 to 30 kg/m2) was significantly associated with RC injury. In the present study, focused only
on individuals with BMI > 30 kg/m2, we found that obesity was not an associated factor for the prevalence or severity
of RC injury. In addition, we evidenced an anticipation in the mean (46 years) and
cutoff point (43 years) of age for the appearance of tendon ruptures from 12 to 15
years, when compared to previous studies.[29] Yamaguchi et al.[29] demonstrated that the mean age for the occurrence of some level of rupture is 58
years, and 68 years for total rupture. The fact that our sample contains only obese
individuals may be an explanation for the difference observed, and suggests that obesity
anticipates the appearance of tendon ruptures.
Similarly, high blood sugar levels have an influence on tendon health.[17] Severe ruptures are six times more common in the presence of more than one cardiovascular
risk factor, such as DM and SAH.[20] Our results demonstrate a higher prevalence of metabolic dysfunctions (DM, SAH)
in patients with RC injury, and an important association between SAH and tendon injury.
Decreased angiogenesis, fibroblast proliferation, collagen synthesis and release of
growth factors are deleterious results observed in diabetic tendons, decreasing the
biomechanical capacity of the tissues and increasing the predisposition to the development
or worsening of tendinopathies.[17]
[18] In a study involving ultrasound RC analysis in patients with diabetes, Abate et
al.[30] demonstrated that even asymptomatic individuals have more advanced degeneration
patterns, especially in the supraspinatus tendon, than individuals without a diagnosis
of diabetes. Gumina et al.,[19] in a study involving 400 patients, concluded that hypertensive individuals were
2 to 4 times more likely to suffer large (involving an entire tendon) and massive
(more than 2 tendons) ruptures of the RC compared to normotensive individuals. The
main explanations for this important evidence are the state of tendon hypoxia generated
by the hypertensive mechanism,[20] even in individuals undergoing pharmacological treatment, since most hypertensive
drugs seem to have greater effect on large vessels, maintaining hypoxia in the tendinous
tissue and thus favoring tissue degeneration.[19]
The findings of the present study should be treated with caution due to the methodological
limitations. Large-scale case-control and cohort studies are needed to obtain an accurate
estimate of the prevalence/incidence and associations of demographic, metabolic and
physical factors with the risk of developing RC. In addition, these results should
be extrapolated to the general population with care, since the study sample was limited
to patients from a specific outpatient clinic. We advocate the need for future studies
to maximize the analysis not only of obesity, but also of the chronic effect of this
comorbidity (exposure time), as a determining factor in the generation of musculoskeletal
dysfunctions.
Conclusion
There was no association regarding obesity and time of exposure to obesity and the
occurrence and severity of RC injury. However, individuals with lesions had longer
exposure to obesity and higher prevalence of metabolic dysfunctions (DM and SAH) than
individuals without RC injury. Furthermore, our findings suggest an important association
regarding SAH and advanced age and RC injury in this population of obese individuals.
