Turkish Journal of Endocrinology and Metabolism, published by Galenos Publishing.
Original Article
42
Amaç: Akromegali hastalarında kemik mineral densitometre (KMD) ve periodontit varlığını ve etkileşimde bulunan faktörleri değerlendirmek.
Gereç ve Yöntem: Kalsiyum-kemik metabolizmasını etkileyen durumu olmayan 47 akromegali olgusu ve 60 yaş-cinsiyet eşleşmiş sağlıklı olgu
çalışmaya alındı. Yaş, cinsiyet, akromegali süresi ve aktivitesi, geçmiş ve güncel tedaviler, hipofiz hormon profilleri ve replasman tedavileri,
periodontal analiz sonuçları kaydedildi.
Bulgular: Yaş ortalamaları 46,6±11,5 yıl olan 18 erkek (%38,3), 29 kadın (%61,7) olgunun 25’inin (%53,1) aktif, 22’sinin (%46,8) inaktif hastalığı vardı.
İnaktif hastalık grubu daha yaşlı idi, hastalık süreleri daha uzundu, sırası ile; p=0,04, p=0,003. Serum kalsiyum, fosfor düzeyleri, 24 saatlik idrar
kalsiyum atımları, femoral ve lomber KMD değerleri ile hastalık aktivitesi ilişkisizdi (p>0,05). Altı hastada (%12,76) osteoporoz saptandı. Periodontit
kontrol grubunda daha sık izlendi; %66,7 ve % 44,7, bu grupta ağırlıklı olarak şiddetli periodontit görüldü; %43,3 ve %12.8, (sırası ile; p=0,022,
p=0,0001). Kronik periodontit sıklığı ve şiddeti, aktif ve inaktif akromegali grupları arasında farksızdı; %48 ve %40,9 (p=0,279). Tekrarlayan
değerlerin varyans analizi testinde, zaman içinde büyüme hormonu değişimi ve periodontit alt grupları anlamlı dağılım göstermedi (p>0,05).
Özet
Address for Correspondence: Hülya Serinsöz MD, Başkent University Faculty of Medicine, Department of Endocrinology, Adana, Turkey
E-mail: hulya.karaoglu@yahoo.com.tr
Received: 25/07/2014 Accepted: 02/02/2015
Purpose: To evaluate bone mineral density (BMD) measurements and the presence of periodontitis in patients with acromegaly, as well as to
inquire the impact of interfering factors.
Material and Method: Forty-seven acromegalic patients with any accompanying condition known to affect calcium-bone metabolism and 60
age-matched healthy controls were included. Age, gender, duration and activity of acromegaly, past-present therapy options, pituitary hormone
profiles, replacement therapies, and the results of periodontal analysis were recorded.
Results: Eighteen patients were male (38.3%), 29 were female (61.7%). The mean age of the patients was 46.6±11.5 years, twenty-five (53.1%)
had active, 22 (46.8%) had inactive acromegaly. The latter were older and had longer disease duration (p=0.04, p=0.003, respectively). Serum
calcium and phosphorus levels, 24-hour urinary calcium excretion and BMD at the lumbar spine and femur neck insignificantly associated with
disease activity (p>0.05). Osteoporosis was detected in 6 patients (12.76%). Periodontitis and advanced periodontitis were more common in
control group (66.7% vs. 44.7%), (43.3% vs. 12.8%) (p=0.022, p=0.0001, respectively). There was no difference in chronic periodontitis and severity
between active and inactive groups (48% vs. 40.9%; p=0.279). No difference was noted in other study parameters, as well. Repeated measures
analysis of variance demonstrated statistically insignificant distribution between GH change in time and periodontitis subgroups.
Discussion: We demonstrated that acromegaly exerted no clear negative impact on vertebral BMD in the absence of overt hypogonadism.
Regardless of disease activity, acromegaly cases exhibited lower rates of periodontitis with less severity which remained unchanged in the
presence of accompanying metabolic disorders known to have negative impact on periodontal tissue. Chronic exposure to excess GH may have
a protective role against periodontitis.
Turk Jem 2015; 19: 42-48
Key words: Acromegaly, bone, growth hormone (GH), periodontitis, osteoporosis
Conflicts of Interest: The authors reported no conflict of interest related to this article.
Abs tract
Başkent University Faculty of Medicine, Department of Endocrinology, Adana, Turkey
*Başkent University Faculty of Dentistry, Department of Periodontology, Adana, Turkey
**Başkent University Faculty of Medicine, Department of Endocrinology, Ankara, Turkey
Hülya Serinsöz, Melek Eda Ertörer, Sibel Başcıl*, Okan Bakıner, Emre Bozkırlı, Neslihan B. Tütüncü**
Akromegali ve Düşük Periodontit Sıklığı: Büyüme Hormonunun Koruyucu
Etkisi Olabilir
Low Prevalence of Periodontitis in Acromegaly: Growth Hormone
May Exert a Protective Effect
DOI: 10.4274/tjem.2687
43
Turk Jem 2015; 19: 42-48
Introduction
Acromegaly is a disorder characterized by growth of many tissues
due to uncontrolled oversecretion of growth hormone (GH) and
insulin-like growth factor-1 (IGF-1) (1). Both GH and IGF-1 play
important roles in calcium and bone metabolism at many steps.
For instance, IGF-1 activates renal 1-hydroxylase enzyme and
inhibits 24-hydroxylase, thus, increases serum calcitriol.
Acromegaly causes periosteal new bone formation, cortical
thickening of the diaphysis of the long bones and joint space
widening. Bone mineral density (BMD) is usually unpredictable
due to interfering factors, predominantly accompanying
hypogonadism in acromegaly (2,3). Eugonadal acromegalic
patients exhibit increased cortical bone BMD at the distal radius,
whereas spinal trabecular bone usually demonstrate insignificant
change (4). In eugonadal acromegalic patients, serum osteocalcin,
urinary hydroxyproline and pyridinoline levels are detected to be
high and lumbar BMD values are within normal limits (5).
In acromegaly, osteoporosis is usually due to accompanying
hypogonadism and results in decrease in lumbar vertebral
BMD. Disease duration, serum IGF-1 levels and hypogonadism
predict the prevalence of vertebral fractures (VF) (1,3). However,
a high rate of incident VF has been reported in both active and
controlled acromegalic patients. In a recent study, progression
of VF has been documented in 20% of cases, despite long-term
biochemical control of acromegaly. Progression of VF has not
been detected to relate with BMD values or BMD changes over
time (6).
Besides frontal bossing and changes in the lips and nose,
growth of the mandibular bone, separation of the teeth, maxillary
widening, and malocclusion of the mouth are frequently
observed in acromegaly (1). Tooth mobility and loss, interdental
spaces (diestema), and, rarely, gingival overgrowth are detected
at periodontal examination. There is scant data about the
periodontal findings in cases with acromegaly.
Periodontal disease is a localised inflammatory reaction of the
tissues surrounding the teeth against bacterial infections (7).
Its presence may be a risk factor for ischemic heart disease,
pulmonary diseases, premature labor, and low birth weight.
Other risk factors associated with periodontal disease are
smoking, traumatic occlusion of the mouth and diabetes mellitus
(8). It is the second well-identified cause for tooth loss and usually
accompanies systemic diseases and is mainly separated into two
main groups; gingivitis and periodontitis.
Gingivitis is an immune response against the microbial dental
plaque located on the teeth and affects more than 90% of the
population. Smoking, medications, pregnancy and hormonal
changes during puberty may act on gingiva. Destruction is limited
to gingiva and is reversible. Gingiva is found to be edematous
and hyperemic (7,9). However, periodontitis is characterised by
irreversible injury in periodontal tissues. Diestema and prominent
tooth mobility are clear signs of periodontitis. Increment in
probing depth, loss of attachment and demonstration of bone
loss radiographically are required for the diagnosis. Periodontitis
is a multifactorial disease and presence of periodontopathogenic
bacteria is not the only factor necessary for its initiation and
progression (10). Systemic diseases; cardiovascular diseases,
diabetes mellitus, syndromes associated with neutropenia,
rheumatoid arthritis, medications, and accompanying genetic
and environmental factors may impact the pathogenesis of
periodontitis and the response of the host to therapy (11).
Studies inquiring the association between periodontitis and
systemic bone density reveal that subjects with low bone density
have less number of teeth, more clinical attachment loss and
more periodontitis. Low systemic bone density has been proposed
to be a risk factor for progression of alveolar bone loss and has
been claimed to increase vulnerability to periodontal destruction.
An association has also been shown between serum estrogen
levels and alteration in alveolar bone mineral density among
post-menopausal women (12,13,14).
High serum GH, IGF-1, insulin-like growth hormone-binding
protein-3 (IGF-1BP-3) and calcitriol levels directly act on bone and
connective tissue in acromegaly. Accompanying hypogonadism,
defects in glucose metabolism, malabsorption due to somatostatin
analogues, which are used in acromegaly treatment, may all
adversely affect the periodontal structures and bone. Besides
hormonal changes, duration and activity of the disease may affect
the course of periodontitis (5,15,16).
In this study, we aimed to evaluate BMD and the presence of
periodontitis in patients with acromegaly and to inquire the impact
of interfering factors.
Materials and Methods
This study was performed at outpatient endocrinology clinics of
Başkent University Faculty of Medicine, Adana, Turkey between
August 2010 and November 2012.
A total of 47 patients with the diagnosis of acromegaly and 60
age-matched healthy controls were included for periodontal
analysis. The study was approved by the Local Ethics Committee
(tracking #: K09/330) and all participants gave written informed
consent.
The exclusion criteria included having any condition known
to affect calcium and bone metabolism, such as being on
Tartışma: Çalışmamızda aşikar hipogonadizm dışlandığında akromegalinin vertebral KMD üzerine negatif etkisi olmadığı gösterildi. Hastalık
aktivitesinden bağımsız olarak, akromegali olgularının periodontit sıklığı düşük bulundu ve bu bulgu periodontal dokuya negatif etkisi olduğu
bilinen, eşlik eden durumlarla da değişmedi. Kronik artmış büyüme hormonu maruziyetinin periodontit bakımından koruyucu olabileceği
sonucuna varıldı.
Turk Jem 2015; 19: 42-48
Anah tar ke li me ler: Akromegali, kemik, büyüme hormone, periodontit, osteoporoz
Çıkar Çatışması: Yazarlar bu makale ile ilgili olarak herhangi bir çıkar çatışması bildirmemiştir.
Özet
Serinsöz et al.
Periodontitis and Acromegaly
44
Turk Jem 2015; 19: 42-48
levothyroxine suppression therapy due to differentiated thyroid
carcinoma, chronic renal failure, hyperparathyroidism, untreated
hypothyroidism and/or hypocortisolism, and bisphosphonate
use. As smoking is known to negatively affect periodontal health,
it was regarded as an exclusion criterion, as well. Additionally, the
participants were instructed not to use any interfering medication,
such as anti-inflammatory and immune-suppressive drugs
throughout the study period.
Physical examination was performed and all the exclusion criteria
were also applied for the participants in control group.
An acromegalic male with central hypogonadism who used
testosterone replacement therapy irregularly and another
male with cured acromegaly who had celiac disease were not
included. Two other acromegalic males with active disease were
also excluded because of their total prosthesis.
The patients were evaluated regarding age, gender, duration and
activity of acromegaly, past therapy options; medical, surgical,
radiotherapy, combination therapies, current medical agents,
pituitary hormone profiles, and replacement therapies.
Active acromegaly was defined if randomly measured GH was
above 2.5ng/dl and IGF-1 above age-corrected limits with/without
medical treatment. Patients with discordant measurements were
considered as active, as well. Other pituitary functions were
determined by evaluating pituitary hormones with end organ
responses and performing dynamic tests where required (17).
Accompanying glucose metabolism disorders; impaired fasting
glucose, impaired glucose tolerance as well as diabetes mellitus,
hypertension and cardiovascular disease were also recorded.
In study group, patients who were on levothyroxine treatment
due to central hypothyroidism with normal free thyroxine levels
were considered euthyroid. Premenopausal women with central
hypogonadism who were on cyclic estrogen/progesterone
therapy were regarded as eugonadal as well as the men who
were on testosterone replacement therapy with normal serum
testosteron levels.
Serum calcium, phoshporus and 24-hour urinary calcium
excretion levels were measured. BMD measurement was
performed at the femoral neck and lumbar spine.
Study and control groups were both subjected to periodontal
examination. Periodontal examinations were performed by
the same experienced periodontist. Periodontal pocket depth
(presence of an abnormal gingival sulcus near the point at which
the gums contact a tooth) was evaluated using periodontal probe
at six different points of each tooth. Individuals with probing pocket
depth (PPD) between 4 mm and 6 mm and clinical attachment
level of (CAL=amount of space between attached periodontal
tissues and a fixed point, usually the cementoenamel junction)
up to 4 mm were diagnosed as having chronic periodontitis with
slight to moderate loss of periodontal support. Those with PPD 6
mm and CAL greater than 4 mm were regarded as having chronic
periodontitis with advanced loss of periodontal support. Bleeding
on probing, which was considered as an objective inflammatory
parameter in periodontitis establishment, was measured using
the gingival bleeding index (GBI). A GBI of ≤0.1 was considered
low risk for the development of periodontitis. Tooth mobility levels
were evaluated and classified as degrees; 1, 2, 3. Radiographic
examination, tooth loss, diastemas (space or gap between two
teeth) and malocclusion were also assessed (18,19).
Laboratory Analyses and BMD Measurements
GH measurements were performed with immunometric assay
(Immulite Growth Hormone, Diagnostic Products Corp., CA, USA),
IGF-1 measurements were done with highly sensitive and specific
immunoradiometric methods (Diagnostic Systems Laboratories,
DSL -5600 ACTIVE). Serum calcium and 24-hour urinary calcium
excretion levels were determined using the colorimetric method
(Roche Modular P-Roche). Serum phosphorus was analysed via
phosphomolibdate method (Architect C16000-ABBOTT).
BMD measurements were performed using dual energy x-ray
absorptiometry (DXA) (Hologic QDR 4500, Hologic IIc., Waltham,
MA, USA) at the lumbar vertebra (L1-L4) and femur neck. T and Z
scores were evaluated using the new NHANES III reference criteria.
Osteopenia (a T score between -1 and -2.5) and osteoporosis (a
T score of less than 2.5) were defined according to the criteria of
the World Health Organization.
Statistical Analysis
The SPSS software (Statistical Package for the Social Sciences,
version 17.0, SSPS Inc, Chicago, IL, USA) was used for statistical
analyses. Categorical variables were given as number and
percentage, continuous variables are presented as means ±
SD, if distributed normally and as median - minimum-maximum,
if distributed not normally. Standard descriptive analysis,
independent samples T-test, the Wilcoxon test, Chi-square,
Mann-Whitney U test, Spearman’s correlation coefficient, and the
repeated measures ANOVA were used where appropriate. A p
value of less than 0.05 was considered statistically significant.
Results
A total of 47 acromegalic patients [18 males (38.3%) and 29
females (61.7%)] with a mean age of 46.6±11.5 years were
included in study. Fourteen subjects (29.8%) were on medical
therapy only, whereas 33 (70.2%) were subjected to combination
therapy, i.e medical therapy following surgery (24-72.2%), medical
therapy following radiotherapy (1-2.1%), and medical therapy
following surgery and radiotherapy (8-24.2%). Of the cases on
medical therapy only; 23 patients (48.9%) were using octreotide,
21 (44.7%) were on octreotide and cabergoline; dopamine agonist
simultaneously, and 3 (6.4%) patients were using pegvisomant
only.
Hormonal assessment of disease activity revealed that 25
(53.1%) patients had active acromegaly, whereas 22 (46.8%)
had inactive disease. Inactive acromegaly group was older and
had longer disease duration (p=0.04 and p=0.003, respectively).
Serum calcium and phosphorus levels, 24-hour urinary calcium
excretion and BMD values at the lumbar spine and femur neck
exhibited insignificant difference between the active and inactive
acromegaly groups. Details are given in Table 1.
Twenty-one patients (44.7%) had glucose metabolism disorder at
various severities. Twenty cases (42.6%) had hypertension and two
(4.3%) had cardiac disease. Active and inactive disease groups
did not differ regarding therapeutic options, glucose metabolism
Serinsöz et al.
Periodontitis and Acromegaly
45
Turk Jem 2015; 19: 42-48
disorders and cardiac disease (p=0.457, p=0.202, p=0.123,
respectively), however, more patients in active acromegaly group
had hypertension, as might be expected (p=0.042).
Among 13 female cases with active disease, nine (69.2%) were
premenopausal, whereas seven (43.8%) were premenopausal
among 16 female cases with inactive acromegaly (p=0.264).
Postmenopausal cases were older (57.1±5.1 years vs. 37.7±5.5
years) and had longer duration of disease [median: 6 (1-17) years
versus median: 2 (1-12)], as may be expected (p=0.039 and 0.001,
respectively). However, they exhibited statistically indifferent
lumbar and femur BMD measurements regarding to disease
activity and menopausal status (p=0.964, p=0.94 and p=0.188,
p=0.469, respectively).
Osteoporosis was detected in 6 subjects (12.76%) in study group.
One acromegalic man exhibited low femur bone density, whereas
five patients-two premenopausal and three postmenopausal
women-demonstrated osteoporosis at the lumbar spine.
Periodontal examination findings in acromegaly and control
groups (n=60) were evaluated. Twenty-six patients with
acromegaly (55.3%) did not exhibit periodontitis. Of 21 patients
(44.7%) with acromegaly and periodontitis; 15 (31.9%) had slight to
moderate periodontitis and 6 (12.8%) had advanced periodontitis.
Twenty-two acromegalic patients (46.8%) exhibited macroglossi.
More number of cases had periodontitis in control group,
advanced periodontitis being dominantly (p=0.022 and p=0.0001,
respectively). Details are given in Table 2.
There was no difference in the total number of cases with chronic
periodontitis between active and inactive acromegaly groups
(48% vs. 40.9%) (p=0.279). There was no statistically significant
difference in severity of periodontitis between the groups, as well
(details are shown in Table 3). The presence of periodontitis also
exhibited any relationship with menopausal state (p=0.521 ). There
was not a relationship between the presence of periodontitis and
menopausal state.
Besides similar periodontal findings, active and inactive
acromegaly groups exhibited statistically insignificant difference
with regard to calcium-BMD analyses.
Study parameters in acromegaly patients (n=47) were compared
with regard to periodontal disease and its severity; 26 subjects
were without periodontitis, 15 were with slight to moderate
periodontitis and 6 patients were with advanced periodontitis.
There was no difference between the groups in terms of serum
calcium and phosphorus levels, final GH and IGF-1 levels,
presence of hypertension, glucose metabolism disorder and/or
cardiac disease (p=0.121, p=0.604, p=0.590, p=0998, p=0.253,
p=0.081, and p=0.782, respectively).
Considering the negative impact of glucose metabolism disorders
on periodontal structures, acromegaly cases were compared with
Serinsöz et al.
Periodontitis and Acromegaly
Tablo 3. Distribution of periodontitis in acromegaly group regarding disease activity
n
Cases without periodontal
pathology (n)
Cases with slight to moderate chronic
periodontitis (n)
Cases with advanced
periodontitis (n)
Active Acromegaly
25
13
7
5
Inactive Acromegaly
22
13
8
1
p
0.625
0.539
0.113
Table 1. Comparison of general features and bone parameters of
active and inactive acromegaly patients
Disease activity
(n=47)
Active group
(n=25)
Inactive group
(n=22)
p
Age (years)
43.4±11.4
50.32±10.7
0.040
Gender (F/M) (%)
52/48
72.7/27.3
0.229
Duration of acromegaly
(year)
2 (1-10)
5 (2-17)
0.003
Serum GH (ng/ml)
4.01 (0.38-56)
0.82 (0.09-2.4)
0.0001
Serum IGF-1 (ng/ml)
417 (232-1356)
173 (57-252)
0.0001
Serum Ca (mg/dl)
9.44±0.38
9.44±0.42
0.989
Serum P (mg/dl)
4.19±0.66
3.93±051
0.143
Urinary Ca (mg/day)
105 (10-380)
105 (10-300)
0.134
Lumbal T score (total)
-0.9 (-4.0-2.0)
-0.65 (-4.0-2.0)
0.842
Femoral neck T score
-0.10 (-3.0-2.0)
-0.1 (-2.0-2.0)
0.375
GH: Growth hormone, IGF-1: Insulin like growth hormone-1
Mean ± Standard Deviation, Median (Minimum-Maximum)
Table 2. Documentation of general features and periodontological
examination of Acromegaly group and Control group
Acromegaly
group
(n=47)
Control
group
(n=60)
p
Age (year)
46.6±11.5
50.32±8.5
0.146
Gender (F/M) (n)
29/18
34/26
0.599
Active/Inactive
Acromegaly (n/n)
25/22
-
-
Glucose Metabolism
Disorder n (%)
21/47 (44.7)
-
-
Cases without periodontitis
n (%)
26/47 (55.3)
20/60 (33.3)
0.023
Total # of chronic
periodontitis n (%)
21/47 (44.7)
40/60 (66.7)
0.022
Slight to moderate
periodontitis n (%)
15/47 (21.9)
14/60 (23.3)
0.321
Advaced periodontitis n (%)
6/47 (12.8)
26/60 (43.3)
0.0001
Macroglossi n (%)
22/47 (46.8)
-
-
46
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Serinsöz et al.
Periodontitis and Acromegaly
regard to the presence of glucose metabolism disorder. Keeping
in accordance with the literature, 13 (61.9%) of 21 patients with the
disorder was found to have chronic periodontitis, while 8 (38.1%) of
26 patients with normal glucose metabolism had periodontitis of
various severity (p=0.043). Presence of other metabolic disorders,
i.e. hypertension or cardiac disease, was found not to associate
with periodontitis.
By taking a T score of 0 as the cut-off value, acromegaly cases
were grouped as the ones with or without osteoporosis/
osteopenia. Twenty-seven patients (57.4%) had lumbar
osteoporosis/osteopenia, whereas femoral osteoporosis/
osteopenia was detected in only 15 subjects (31.9%). Disease
activity exhibited no impact on the presence of osteoporosis/
osteopenia at lumbar and femoral BMD (p=0.533 and p= 0.177,
respectively). Presence of periodontitis did not show a relationship
with osteoporosis/osteopenia at either site, as well (p=0.369 and
p=0.549). Repeated measures analysis of variance performed to
investigate the relationship between the GH change in time at
least three sequential time points and periodontitis subgroups
exhibited (GH change in time at least three sequential time points
and periodontitis subgroups), statistically insignificant distribution
[GH (median: minimum-maximum); GH1: 10.0 (0.52-40.0), GH2:
6.89 (0.38-200), GH3: 4.53 (0.35-56)].
Discussion
GH has been demonstrated to act on bone via interacting directly
on GH receptors on osteoblasts and via increasing local IGF-1
production (autocrine and paracrine effect). IG-1 contributes
to the differentiation of osteoblasts. GH deficiency has been
demonstrated to associate with bone loss and osteoporosis,
however, the impact of excess GH on bone tissue is less clear
(20,21,22). In the present study investigating bone density and
periodontital tissue, a new site of trabecular bone, among
acromegaly cases, no statistically difference was found between
active and inactive acromegaly subgroups in serum calcium
and phosphorus levels, urinary calcium excretion and BMD
measurements in the presence of similar rates of periodontitis.
Periodontitis has been detected less frequently with less severity
in study group. Severity of periodontitis has also been shown
not to associate with accompanying metabolic problems, e.g.,
hypertension, cardiac disease or glucose metabolism disorder,
and with biochemical and hormonal parameters, such as serum
calcium, phosphorus, GH and IGF-1 levels and menopausal
status. Thus, acromegaly seems to exert a protective effect against
periodontitis with neutral effect on vertebral BMD in the absence
of overt hypogonadism.
Active acromegaly in the presence of high serum GH and IGF-1
levels have been shown to impair bone quality and increase
the risk of bone fragility. It has been detected to associate with
hypercalciuria and negative calcium balance (23). High bone
turnover has been detected by measuring changes in biochemical
markers of bone metabolism and histomorphometry among
acromegalic patients.
Markers for bone turnover, predominantly the resorption
markers, have been shown to increase and the latter have been
demonstrated to correlate positively with serum GH and IGF-1 (24).
However, keeping in accordance with our findings, the negative
effects mentioned above have not been shown in DXA-BMD
measurements and normal or even high bone density has also
been demonstrated in acromegaly (25).
We have performed a liberal selection bias for excluding
hypogonadism and found out that disease activity exhibited
no clear impact on BMD in acromegaly. In addition, there was
no statistically significant difference between pre-menopausal
acromegalic patients and their older postmenopausal peers
in BMD values. Our finding is compatible with the literature
reporting the neutral effect of acromegaly on vertebral BMD in
the absence of hypogonadism (4,5). However, one can argue
that inactive acromegaly cases and the postmenopausal ones
in this study were older and naturally had longer duration of
disease, thus, this may have blunted their axial BMDs. DXA, the
method we performed is currently the most commonly used one
for determining bone health. However, it has some limitations.
Atherosclerotic plaques, vertebral deformities and osteoarthritis
may cause falsely high BMD measurements. Besides, DXA
measures areal BMD-grams per square centimeter - and
its 2-dimensional (2D) BMD measurement may probably be
negatively affected by bone enlargement in acromegaly. It also
does not give details about cortical and trabecular bone and
bone micro-architecture which are very important for fracture
risk assessment (24). High-resolution quantitative computed
tomography (HR-QCT) is a method that permits the in vivo
assessment of the bone micro-architecture and the volumetric
BMD. Its measurements are comparable to 2D histomorphometry
and 3D microcomputed tomography of transiliac bone biopsies
(25). In a very recent study, the negative effect of acromegaly has
been demonstrated on trabecular bone microarchitecture using
HR-QCT in the distal radius and tibia in eugonadal patients. In
that study, hypogonadism has been strictly defined and, besides,
young acromegalics without sex hormone replacement therapy
and postmenopausal women have also been excluded. This
approach has resulted in a younger group of patients with shorter
duration of disease and less contributing factors. However, the
resultant relatively low number of participants necessitates this
study to be re-performed on a larger number of eugonadal
acromegalic patiens by using vertebral HR-QCT (26).
We were unable to exclude our postmenopausal patients due
to low number of participants and that may be considered as
a limitation of our study. However, a complementary parameter,
periodontal analysis, was performed in addition to DXA to
investigate an additional area of trabecular-alveolar bone.
We assume that lower rates of chronic periodontitis among
acromegalic patients support the reliability of our DXA-BMD
measurements.
Our findings impose the idea that in the absence of overt
hypogonadism, excess GH may not have a negative effect on
trabecular BMD. Nevertheless, it should be kept in mind that
normal BMD does not imply a risk-free profile for vertebral
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Serinsöz et al.
Periodontitis and Acromegaly
fractures. Progression of VF in controlled acromegaly cases with
normal BMD is a supportive observation for this proposal (6).
Periodontitis is an important area of interest for periodontists
due to the fact that it causes irreversible destructive injury to
alveolar bone and the net effects of GH and IGF-1 on periodontal
structures are not clear. Osteoblast are regulator cells of bone
metabolism, they limit bone matrix synthesis or bone resorption
under various conditions. Human periodontal ligament cells
(PDL) act like osteoblasts; they are the master cells regulating
the resorption and synthesis of connective tissue of periodontal
structures (27,28). GH is an important factor acting on the gingival
tissue and alveolar bone. Besides their effects on osteoblasts, GH
and IGF-1 have been demonstrated to increase the secretion of
bone morphogenic protein-2 (BMP-2) and bone morphogenic
protein-4 (BMP-4) from human dental pulp fibroblasts (29). GH
has been reported to increase alveolar bone formation in an
experimental study on rat periodontium (30). Accordingly, in a
recent study, acromegalic patients have been shown to exhibit
less periodontitis (8). This effect may be partially attributed to the
not negative impact of acromegaly on trabecular bone (4). The
findings of our study are compatible with the data mentioned
above. It is possible that chronic exposure to excess GH may
even have a protective effect against periodontitis. Knowing that
postmenopausal state is a risk factor for periodontitis, detection
of similar number of postmenopausal and premenopausal cases
with periodontitis in our cohort is a supportive data to the above
mentioned data (14). After grouping our cases with regard to the
presence of osteoporosis/osteopenia, it was observed that there
was no difference in the prevalence of periodontitis between the
groups. We were unable to demonstrate the protective effect of
chronic excess GH exposure on the periodontal tissue statistically
by using the repeated measures analysis of variances, however,
we assume that if the number of acromegalic participants could
be increased, the statistical significance would be evident.
Our study has some limitations. The relatively low number of
participants is one of them, and therefore we had to perform a
liberal approach regarding the inclusion of hypogonadal patients.
Not performing HR-QCT and not measuring resorption markers
are the other limitations.
In conclusion, in the present study, we have demonstrated that
acromegaly exerts no clear negative impact on vertebral BMD
in the absence of overt hypogonadism. Regardless of disease
activity, acromegaly cases exhibit lower rates of periodontitis
with less severity which remains unchanged in the presence
of accompanying metabolic disorders known to have negative
effects on the periodontal tissue. Chronic exposure to excess
GH may have a protective role against periodontitis. We believe
this information requires to be confirmed by studies with larger
sample sizes.
Acknowledgement: Many thanks to Çağla Sarıtürk for her
contribution for statistical analysis.
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